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Morozkina, Vera E. Sitnikova, Yuliya Е. Generalova, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8759759/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Mangiferin, a natural antioxidant with demonstrated therapeutic potential against a range of serious diseases, faces significant limitations in clinical application due to its extremely low water solubility and poor bioavailability. To address these challenges, this study reports the fabrication and characterization of a novel nanofiber drug delivery system that integrates mangiferin into a biocompatible polymer matrix composed of poly (vinyl alcohol) (PVA) and chitosan (CS). Using a three-component solvent system, the electrospun solution achieved a mangiferin content 5 to 10 times higher than its aqueous solubility, resulting in nanofibers containing 6.7 to 12.5% mangiferin by weight. Optimization of electrospinning parameters identified 4% PVA, 3% CS, 0.5% mangiferin, 45% CH 3 COOH, and 15% C 2 H 5 OH as the optimal formulation, with a 150mm needle-collector distance, 0.2 mL/h feed rate, and 28 kV voltage, yielding uniform nanofibers with an average diameter of 332 ± 84 nm. UV-Vis spectra confirmed the stability of mangiferin in solution for at least 40 days at room temperature, while IR spectra indicated strong interactions between mangiferin and the polymer matrix. Increasing mangiferin loading slightly reduced overall crystallinity and increased cell size, influencing the glass transition, melting behavior, thermal decomposition, and mechanical properties of the nanofibers. These findings demonstrate that PVA–CS–mangiferin nanofibers are a promising platform for enhancing the solubility, stability, and controlled release of mangiferin, supporting their potential application in advanced drug delivery systems. mangiferin poly (vinyl alcohol) chitosan nanotechnology drug delivery system electrospinning Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Highlights • The electrospinning solution can carry 5–10 times more mangiferin than its solubility. • Mangiferin was stable in the electrospinning solution after 40 days at room temperature. • Determined the optimal strategy for producing mangiferin-blended PVA-CS nanofibers; • Electrospun nanofibers can contain up to 12.25% medication. • Electrospun nanofibers can be stored in water for up to 4 months. 1. Introduction In the context of personalized medicine, the most urgent challenge is developing drug delivery systems that incorporate biologically active substances, particularly antioxidants, due to their broad therapeutic potential in treating gastrointestinal disorders, diabetes, and cancers. Importantly, diseased and healthy differ in both their characteristics and microenvironment; while healthy typically maintain a neutral or slightly extracellular pH of 7.1–7.4 [1, 2], diseased cells generally exhibit a more acidic microenvironment. In inflammatory conditions such as tumors, the extracellular pH becomes increasingly acidic, ranging from 7.2 to 6.5, and can decrease to 5.4 within tissues. Similarly, myocardial ischemia and hematomas associated with fractures exhibit pH values of 5.7 and 4.7, respectively [1, 3]. Another key distinction between abnormal (particularly cancerous) and healthy cells is their metabolic pathway: cancer cells convert glucose to lactic acid rather than CO 2 and water (Warburg effect, 1956)[1, 4], resulting in an acidic, negatively charged microenvironment with elevated lactate ion concentration. Cancer cells preferentially utilize glucoside molecules for proliferation [4, 5], making them more likely to absorb molecules with basic, positively charged, and glycoside structures. These properties can be leveraged for targeted drug delivery, as such compounds are selectively taken up by diseased cells. Additionally, molecules with antioxidant activity and functional groups such as alcohol, phenol, carbonyl, and conjugated π-bonding systems can inhibit disease progression and support cellular recovery. Mangiferin is broadly distributed among plant species, particularly within the Anacardiaceae and Gentianaceae families [6]. Mangiferin can be extracted from multiple plant parts, including leaves, bark, stem, fruit peel, and roots, and is recognized as one of the most potent naturally occurring antioxidants [7–10]. Among dietary sources, honeybush tea ( Cyclopia sp .) in South Africa is particularly notable, with dried leaves containing up to 4% mangiferin by weight [10]. Since its initial isolation from mangoes ( Mangifera indica L ., Anacardiaceae ) in 1908, extensive research has elucidated its composition, structure, and properties. Mangiferin is classified as a xanthonoid, specifically norathyriol glucoside [7, 8]. Mangiferin, the molecular structure of which is illustrated in Fig. 1 , comprises eight hydroxyl groups: four located within the glucopyranosyl moiety and four others directly bonded to the xanthone skeleton. The hydroxyl groups associated with the glucopyranosyl unit exhibit comparatively lower acidity than those attached to the xanthone scaffold. Specifically, the hydroxyl groups at positions C 1 , C 3 , C 6 , and C 7 are expected to display enhanced acidity, as previously reported [11, 12]. Owing to the formation of a condensed ring system, rotational freedom around the C–C bonds is restricted. The structure elucidation of mangiferin was achieved in the 1960s [7, 13], revealing its classification as a polyphenolic compound covalently linked to a glucose residue via a C–C bond. Mangiferin has demonstrated significant therapeutic potential across a broad spectrum of pathological conditions. Traditionally used in ethnomedicine, mangiferin-rich plants have been applied in the management of cardiovascular disease, infections, hypoglycemia, burns, liver disease, and cancers [7, 10, 14, 15]. Extensive pharmacological investigations have revealed that mangiferin possesses a diverse array of bioactivities, including analgesic, antidiabetic, antisclerotic, antimicrobial, antiviral, cardioprotective, hepatoprotective, neuroprotective, anti-inflammatory, and antiallergic effects [14, 16]. Notably, mangiferin inhibits antiviral efficacy against several clinically relevant viruses. It has been shown to inhibit the replication of influenza viruses [17], herpes simplex type I [18], herpes, and lifelong infections [19]. Furthermore, mangiferin effectively suppresses HIV-1 replication in a dose-dependent manner [17], and has been identified as a promising candidate for treating poliovirus infections [20]. Beyond its antiviral properties, mangiferin also exerts additional biological effects, including analgesic, antipyretic, gastroprotective, anti-cryptosporidium, anti-allergic, and radioprotective activities [21]. Numerous in vitro and in vivo studies have consistently demonstrated the potent biological activities of mangiferin. However, despite its promising pharmacological potential, mangiferin has not garnered sufficient scientific or clinical attention. This limited interest is primarily attributed to its poor oral bioavailability and low aqueous solubility[22, 23]. Mangiferin exhibits limited solubility in ethanol, is marginally soluble in water (0.111 mg/mL) [23], and is practically insoluble in non-polar solvents, such as n-hexane and diethyl ether [24]. The oral bioavailability of mangiferin is reported to be approximately 1.2% [25]. This limitation could be attributed to mangiferin's low lipophilic features, poor intestinal membrane permeability, and limited oral absorption [26]. These pharmacokinetic drawbacks significantly hinder the clinical translation and therapeutic application of mangiferin. Consequently, only a limited number of mangiferin-based products are currently available on the market. Among them, the most recognized is Vimang, a phytopharmaceutical derived from the aqueous extract of Mangifera indica containing approximately 20% mangiferin [27]. Vimang is commercially formulated as tablets, creams, and syrups, and is primarily used in the supportive treatment of various cancer types [6]. The therapeutic impact of mangiferin is constrained by its extremely poor oral bioavailability. To address this limitation, encapsulation within natural polymeric matrices has been explored as a strategy to enhance its loading capacity, controlled release, and systemic bioavailability. Typically, the complexes mangiferin–phospholipid and mangiferin–phospholipid–polysorbate-80[28, 29] have demonstrated improved solubility profiles. Similarly, formulations incorporating mangiferin with pluronic F127, pluronic P123, vitamin E, and TPGS[30] have yielded favorable solubilization outcomes. Mangiferin-hyaluronic acid (HA) nanoparticles exhibited droplet sizes ranging from 194.5 to 397.9 nm, with a negative zeta potential (<-30 mV) and maintained physical stability up to 30 days at 4°C. Nanoparticles formulated with short-chain HA nanoparticles (40–50 kDa) presented reduced particle size, enhanced negative surface charge, and a 2.5-fold increase in permeability compared to unformulated mangiferin (Q 24 = 5.04 ± 0.01 µg/cm 2 ). Furthermore, the combination of transcutola-P resulted in a 5-fold enhancement in permeability (Q 24 = 9.41 ± 0.01 µg/cm 2 ) [29]. Besides, the incorporation of mangiferin into an ethylene vinyl acetate copolymer containing sorbitol ether (Span®20) resulted in a marked enhancement of the polymer film's antioxidant activity up to 80% [31]. Additionally, polylactic acid-mangiferin nanoparticles produced by emulsion solvent evaporation revealed antiproliferative activity in vitro on BEAS 2B and HEPG2. These nanoparticles exhibited resistance to gastrointestinal digestion for up to 1.5 hours and did not adversely affect the metabolism or biological activity of healthy cells [32]. In addition, mangiferin-loaded carrageenan/CS core-shell hydrogel beads displayed a delayed and sustained release profile for mangiferin, while maintaining non-toxicity and supporting high cell viability[33]. Preliminary swelling and in vitro release studies identified polyvinyl alcohol, CS, and gelatin hydrogels as the most suitable matrices for controlled mangiferin release in aqueous media at pH values of 5.5 and 10.0 [34]. Most existing studies have focused on the development and characterization of polymer nanoparticles encapsulating mangiferin [35]. In contrast, research on polymer fibers incorporating mangiferin remains scarce. To address this gap, the present study investigates the integration of mangiferin into PVA and CS nanofibers. PVA and CS were selected as the primary matrix materials due to their biosafety, physiological activity, extensive biomedical applications, and abundant availability[36,37]. PVA is a hydrophilic polymer with a poly alcohol structure, enabling hydrogen bonding and excellent water solubility. These properties make PVA an effective carrier for poorly water-soluble compounds such as mangiferin. Given that water constitutes 55% to 78% of the human body, depending on age and gender, with making up 31% of bones, 73% of the heart and brain, 79% of muscles and kidneys, and 83% of the lungs [36]. As a result, the use of water-soluble polymers facilitates systemic distribution, except in adipose tissues. PVA is widely recognized for its abundance, non-toxicity, biosafety, and high biocompatibility [37–42]. Consequently, it is extensively applied in biomedical fields, including eye drops, contact lenses, ocular inserts, ocular films, nanoparticles, microspheres, floating microspheres, mucoadhesive, targeted drug delivery systems, soft tissue, articular cartilage, intervertebral disc nucleus, artificial skin, and vocal cords,... [37, 43]. The chemical structure of CS makes it an excellent candidate for targeted drug delivery systems [46]. Its polysaccharide backbone, combined with basic and positively charged amine functional groups [44, 45], enhances its affinity for diseased cells. Due to its solubility in acidic media and insolubility in neutral and basic environments, CS enables both targeted drug delivery and controlled drug release at the intended site. Numerous studies have demonstrated that CS is safe, non-toxic, biodegradable, and biocompatible [45, 46], and it exhibits beneficial biological activities, including antibacterial, antioxidant, and anti-inflammatory effects [44, 45, 47, 48]. Consequently, CS is widely used in food and medical applications, including orthopedics and periodontics, drug delivery systems, wound healing, and tissue engineering [49]. The incorporation of mangiferin, as the active pharmaceutical ingredient, PVA as the delivery matrix, and CS as the directional material presents a promising strategy for targeted drug delivery system design. This study provides a comprehensive investigation into the electrospinning fabrication of PVA-CS-mangiferin nanofibers, with detailed analysis of solution composition, processing parameters, fiber morphology, and the resulting physicochemical properties. 2. Materials and Methods 2.1. Materials PVA (molecular weight: ~ 75 kDa, GOST TU: GOST 10779-78) and CS ( molecular weight: 200 kDa, TU 9289-067-00472124-03) were used to fabricate PVA-CS nanofibers for mangiferin incorporation. Mangiferin (C 19 H 18 O 11 , CAS No 4773-96-0, molecular weight 422.37, purity 98%) was purchased from Gute Chemie-abcr. The solvent system consisted of distilled water, acetic acid (99.5%), and ethanol (98%). 2.2. UV-Vis spectroscopy analysis The presence and release of mangiferin in solutions and from nanofiber matrices were evaluated using a UNICO UV/Vis spectrophotometer (USA) with a wavelength range of 190–1100nm, and a resolution of 1 nm. 2.3. Electrospinning Technique Electrospun nanofibers were fabricated using a NANON-01A electrospinning system (MECC CO., LTD., Fukuoka, Japan). The process was conducted at 28.0 ± 2.0°C and 21 ± 3% relative humidity. Key parameters were systematically varied, including voltage (16–30 kV), feed rate ( 0.1–0.4 mL/h), and needle-to-collector distance (100 mm – 150 mm). Electrospinning was performed using a 16G steel needle, a horizontal speed of 10 mm/s, and a stainless steel receiver plate (150 mm × 200 mm). The nanofiber matrices for mechanical and drug release studies were collected from the device's rotating drum at 500 rpm. 2.4. Morphology and Diameters of Nanofibers Preliminary characterization, morphology, and diameter measurements of electrospun fibers were performed using an Olympus STM6 optical microscope (OLYMPUS Corporation, Tokyo, Japan). The differential interference contrast (DIC) technique was employed to enhance fiber color and contrast. Nanofiber diameters were analyzed using ImageJ software (National Institutes of Health, Bethesda, MD, USA). 2.5. Fourier-transform infrared (FTIR) spectroscopy Attenuated total internal reflection (ATR) FTIR spectra were acquired in the 4000 − 600 cm –1 range using a Bruker Tensor 37 FTIR spectrophotometer equipped with a diamond-coated ZnSe crystal (MIRacle, Pike). Spectra were recorded at a resolution of 2 cm –1 , averaging 32 scans. 2.6. X–ray diffraction (XRD) analysis Wide–angle X–ray diffraction (XRD) profiles of PVA powder, CS powder, and nanofibers were obtained at room temperature using a DRON–8 X–ray unit equipped with a BSV–29 sharp confocal tube ( copper anode), a NaI (Tl) detector, and a β-filter (Ni). Flat surface samples were placed on glass slides for analysis. The 2θ range for the samples was 10–60°. The average crystallite size was calculated using the Scherrer formula: τ = K λ/β cos θ where τ is the average crystallite size, K is the shape factor (0.98 rad), λ is the X–ray wavelength (1.54 Å), β is the full width at half maximum (FWHM) of the diffraction peak, and θ is the Bragg angle. The normalized area of the diffraction peaks was used to determine the degree of crystallinity [50]. 2.7. Differential scanning calorimetry (DSC) analysis Differential scanning calorimetry (DSC) was performed using a DSC 204 F1 Phoenix instrument (Netzsch, Germany). Samples (~ 2 mg) were analyzed in closed aluminum crucibles under nitrogen flow (protective gas: 80 mL/min, working gas: 30 ml/min) over a temperature range of – 30°C to 300°C, at a heating/cooling rate of 10 K/min. To remove the adsorbed moisture, samples were heated from room temperature to 150°C. Before analysis, samples were heated to 150°C to remove adsorbed moisture, held for 5 minutes, then cooled to – 30°C. Air was used as the reference. The degree of crystallinity ( χ c ) was calculated using the following equation: χ c = (∆H / m ∆H o ) × 100 where m is the polymer mass, ∆H is the enthalpy of sample melting, and ∆H o is the enthalpy of fusion of 100% crystalline PVA (150 J/g) [51]. 2.8. Thermogravimetric analysis (TGA) The thermal properties of the initial components and the resulting nanofibers were evaluated using a TG 209 F1 Libra thermogravimetric analyser (Netzsch, Germany). Analyses were conducted over a temperature range of 25°C to 900°C at a heating rate of 10°C/min under a nitrogen atmosphere (gas flow: 40 mL/min), using Al 2 O 3 crucibles. 2.9. Tensile property Tensile properties were evaluated using an Instron 5943 tensile testing machine (Instron, USA) at room temperature and crosshead speed of 50 mm/min in accordance with ISO 527-3 standards [52]. 2.10. High Performance Liquid Chromatography (HPLC) Mangiferin release was analyzed using a Shimadzu LC-10 UV detector (Shimadzu, Japan) and a Millichrome-A02liquid chromatograph equipped with an ultraviolet detector (OOO IH "EkoNova", Russia). Chromatographic separation was performed on a Waters SunFire C18 column (3.5 µm, 3.0×150 mm). The mobile phase consisted of 0.1% phosphoric acid and acetonitrile (85:15 v/v) at a flow rate of 0.4 mL/min. The injection volume was 20 µL, and the column temperature was maintained at 37 ° C. 2.11. Statistical Analysis Nanofiber diameter distributions were analyzed from micrographs using OriginPro 2019b (OriginLab Corporation, Northampton, MA, USA). Lattice parameters of polymer powders and nanofibers were determined by analyzing DSC and XRD data with OriginPro 2019b, and X'Pert Highscore software (PANalytical, 2009) with the DICVOL04 indexing program. 3. Results and Discussion All concentrations used in this study were expressed as a percentage of weight (%, wt./wt.) and simply denoted as %. Solutions of 4% PVA, 3% CS, 15% ethanol, and 45% acetic acid with various concentrations of mangiferin were prepared on a magnetic stirrer at 90°C. 3. 1. Mangiferin solutions There are limited investigations on the physicochemical behavior of mangiferin in solutions and its interactions with polymer matrices[11]. Carrier polymers capable of non-covalent interactions, such as CS, can form inclusion complexes with hydrophobic bioactive substances, thereby enhancing their solubility in biological fluids. Mangiferin has eight hydroxyl groups: four are directly affixed to the xanthone skeleton, and four are located in the glucopyranosyl system. The fused ring structure restricts the free rotation of the C-C bonds. The hydroxyl functions act as both hydrogen bond donors and acceptors, resulting in stable hydrogen bonding throughout the crystallization of water molecules [53]. Mangiferin exhibits pH-dependent behavior; for example[11], a mangiferin solution in DMSO-water (80 − 20) has a pH of 4.2 [11]. At pH about 7.0, the C 6 hydroxyl group is deprotonated first, followed by C 7 , and at pH 8.2, C 3 is deprotonated (see Fig. S1 ). The formation of an intramolecular hydrogen bond between C 1 -OH and the keto group was confirmed by NMR. Upon addition of alkali, the hydroxy groups in ring B are primarily affected, while C 1 -OH remains largely unchanged. pH changes also induce bathochromic shifts in the UV spectra [11]. [11] [11] a. UV-Vis spectral changes of mangiferin in solvents Three solutions comprising 0.001% mangiferin in distilled water, a solvent of 60% ethanol, and a combined solvent of 15% ethanol-45% acetic acid were prepared. UV-Vis spectral alterations of these solutions were recorded at the wavelength range of 200–400 nm at 25 ° C (Fig. 2 ). Absorption of UV light in the 200–400 nm range promotes electrons from ground state orbitals to higher energy orbitals, specifically from the highest occupied molecular orbital (HOMO) to the lowest unoccupied molecular orbital (LUMO) [54]. The addition of ethanol and acetic acid to the mangiferin solution results in a hypsochromic shift (shift to lower wavelengths) and increased absorption. This effect is attributed to the ability of ethanol, water, and acetic acid to form hydrogen bonds with mangiferin, thereby altering its absorption bands and shifting the energy gap between the two electronic states. Furthermore, as an aromatic chemical, mangiferin exhibits changes in peak intensity and position in response to pH-induced disturbances of its conjugated system [54]. According to the Vietnamese Pharmacopoeia, the ultraviolet absorption spectrum of mangiferin ethanol exhibits maximum absorption at 241 ± 2 nm, 258 ± 2 nm, 316 ± 2 nm, and 366 ± 3 nm [12]. b. Mangiferin in polymer solutions While numerous works have explored mangiferin-polymer solutions, most focus on nanoparticle formation rather than nanofiber fabrication, and few investigate the structure interactions between mangiferin and the polymer matrix. For example, Pipattanawarothai et al. [34] reported that in hydrogels composed of PVA, CS, and gelatin loaded with mangiferin, the predominant interactions occurred between mangiferin and the functional groups of PVA macromolecules rather than CS. To investigate the loading of mangiferin into the polymer matrices, a system containing 4% PVA, 3% CS, 45% acetic acid, and 15% ethanol was employed. This polymer system was used throughout the entire study. Solutions of mangiferin and PVA–CS–mangiferin were prepared in a ternary solvent system of water, acetic acid, and ethanol, and subjected to UV analysis in the wavelength range from 220 to 400 nm at various time points. Figure 3 demonstrates that the characteristic absorption peak of mangiferin at 366 nm remained constant after 40 days, indicating the stability of the polymer system. 3.2. Investigation of mangiferin concentration for integration into nanofibers The possibility of forming fibers from electrospun solutions of PVA–CS–mangiferin with the addition of 0.01%, 0.1%, 0.5% and 1% mangiferin in the ternary solvent system was studied. The fabrication of PVA–CS nanofibers incorporated with mangiferin was systematically investigated under a range of electrospinning parameters. Specifically, the needle–collector distance was varied between 100 and 150 mm, the feed rate was adjusted from 0.1 to 0.2 mL/h, and the applied voltage ranged from 16 to 30 kV. The results presented in Table 1 summarize the influence of mangiferin concentration on the formation and morphology of the resulting nanofibers. Table 1 Results of the formation of PVA–CS–mangiferin nanofibers at various concentrations of mangiferin under electrospinning conditions: needle–electrode distance 100–150 mm, feed rate 0.1–0.2 mL/h, voltage 16–30 kV. Needle–electrode distance (mm) Feed rate (mL/h) Mangiferin concentration (% w/w) Voltage (kV) 16 18 20 22 24 26 27 28 29 30 150 0.1 0 O o + + + + + + + + 0.01 O o + + + + + + + + 0.1 O o + + + + + + + + 0.5 O + + + + + + + + + 1.0 O o + + + + + + + + 0.2 0 O O o + + + + + + + 0.01 O o + + + + + + + + 0.1 O o + + + + + + + + 0.5 O o + + + + + + + + 1.0 O o o o + + + + + + 140 0.1 0 O o + + + + + + + + 0.01 O o + + + + + + + + 0.1 O o + + + + + + + + 0.5 O + + + + + + + + + 1.0 O o o + + + + + + + 0.2 0 O O * + + + + + + + 0.01 O o + + + + + + + + 0.1 O o + + + + + + + + 0.5 O o + + + + + + + + 1.0 O o o + + + + + + + 120 0.1 0 o + + + + + + + + + 0.01 O o + + + + + + + + 0.1 O o + + + + + + + + 0.5 O + + + + + + + + + 1.0 O o + + + + + + + + 0.2 0 O o + + + + + + + + 0.01 O o + + + + + + + + 0.1 O o + + + + + + + + 0.5 O * + + + + + + + + 1.0 O o o + + + + + + + 100 0.1 0 o + + + + + + + + + 0.01 O + + + + + + + + + 0.1 O + + + + + + + + + 0.5 O + + + + + + + + + 1.0 O + + + + + + + + + 0.2 0 o * + + + + + + + + 0.01 O o + + + + + + + + 0.1 O o + + + + + + + + 0.5 O + + + + + + + + + 1.0 O + + + + + + + + + (O) Formation of drops and a few fibers. (o) Formation of nanofibers and a few drops; (+) Formation of nanofibers; (*) Formation of fibers, but the process is unstable The results presented in Table 1 demonstrate that the incorporation of mangiferin at concentrations ranging from 0.01% to 0.5% into the electrospinning solution did not adversely affect the fiber formation process. However, when the mangiferin concentration was increased to 1.0% the electrospinning process exhibited instability and complications, suggesting an upper threshold for effective drug loading under the tested conditions. Representative microscopic images and the corresponding diameter distributions of PVA–CS–mangiferin nanofibers, electrospun at a needle–collector distance of 140 mm, a feed rate of 0.2 mL/h, and an applied voltage of 28 kV, are shown in Figure S2 and summarized in Table 2 . Table 2 Description of the diameter of electrospun nanofibers from a solution of 4% PVA–3% CS–mangiferin solutions, and electrospinning parameters fixed at the collector-needle distance of 140 mm, the feed rate of 0.2 mL/h, and the voltage of 28 kV. Fiber diameter (nm) Mangiferin concentration (% w/w) 0.0 0.01 0.1 0.5 1.0 Mean 285 304 334 334 343 Standard deviation 65 92 90 101 83 Minimum 121 105 120 137 172 Maximum 592 647 646 671 681 As seen in Table 2 , increasing mangiferin concentration to 1.0% resulted in a 40% increase in the average fiber diameters. These results indicate that the addition of mangiferin to the polymer spinning solution has a substantial impact not only on the morphological properties of the resulting nanofibers but also on the overall electrospinning behavior. It is additionally proven that a system consisting of 4% PVA, 3% CS, 0.5% mangiferin, 45% acetic acid, and 15% ethanol is most appropriate for further research. To further improve the quality and performance of PVA–CS–mangiferin nanofibers, it is essential to optimize the technological parameters of the electrospinning process. 3.3. Investigation of electrospinning technological parameters A systematic investigation into the optimization of electrospinning parameters for the fabrication of PVA–CS–mangiferin nanofibers was conducted. The effects of needle–collector distance, feed rate, and applied voltage were evaluated to determine their influence on fiber morphology and quality. The results demonstrated that increasing the needle–collector distance from 120 mm to 150 mm, while maintaining a feed rate of 0.2 mL/h and a voltage of 28 kV, resulted in nanofibers with the smallest average diameters and the lowest incidence of defects, as shown in Figure S3 and Table 3 . Table 3 Description of the diameter of electrospun nanofibers from a solution of 4% PVA − 3% CS – 0.5% mangiferin solutions, and electrospinning parameters at collector-needle distance of 120–150 mm, feed rate of 0.2 mL/h, and voltage of 28 kV. Fiber diameter (nm) Collector – needle distance (mm) 120 130 140 150 Mean 401 388 334 332 Standard deviation 133 119 101 84 Minimum 147 155 137 172 Maximum 779 735 671 623 Further analysis of feed rate (0.1–0.4 mL/h) at a fixed distance of 150 mm and voltage of 28 kV revealed that a feed rate of 0.2 mL/h produced the most uniform fibers with minimal defects (Figure S4, Table 4 ). Table 4 Description of the diameter of electrospun nanofibers from a solution of 4% PVA – 3% CS – 0.5% mangiferin solutions, and electrospinning parameters at collector-needle distance of 150 mm, feed rate of 0.1–0.4 mL/h, and voltage of 28 kV. Fiber diameter (nm) Feed rate (mL/h) 0.1 0.2 0.3 0.4 Mean 350 332 387 415 Standard deviation 93 84 141 120 Minimum 163 172 137 185 Maximum 646 623 809 799 Additionally, varying the applied voltage between 26 and 30 kV indicated that 28 kV was optimal for achieving consistent fiber morphology and diameter distribution (Figure S5, Table 5 ). Table 5 Description of the diameter of electrospun nanofibers from a solution of 4% PVA–3% CS – 0.5% mangiferin solutions, and electrospinning parameters at collector-needle distance of 150 mm, feed rate of 0.2 mL/h, and voltage of 26–30 kV. Fiber diameter (nm) Voltage (kV) 26 27 28 29 30 Mean 383 361 332 361 370 Standard deviation 91 130 84 92 94 Minimum 170 158 172 100 148 Maximum 658 743 623 696 646 Collectively, these findings establish that the optimal electrospinning parameters for producing high-quality PVA–CS–mangiferin nanofibers are the needle-electrode distance of 150 mm, the feed rate of 0.2 ml/h, and the applied voltage of 28 kV. 3.4. Investigation of the properties of nanofibers integrated with mangiferin 3.4.1. Fourier-transform infrared (FTIR) spectroscopy FTIR spectroscopy was conducted on samples of PVA–CS–mangiferin nanofibers with varying mangiferin concentrations. Spectra of pure PVA, CS, and mangiferin powders were also obtained for comparison. The analysis confirmed complete solvent removal from the nanofiber matrix, as evidenced by distinct spectral differences between the solution and the final nanofiber samples. Figure 4 displays the infrared spectra for all initial materials, the solution, and the PVA–CS–mangiferin nanofiber mats. The mangiferin spectrum exhibits a characteristic absorption band at 3365 cm − 1 corresponding to phenolic OH stretching [55, 56]. Aliphatic C–H stretching vibrations from the glucose moiety appear at 2939 cm − 1 [30, 57] and 2914 cm − 1 [58]. The C = O carbonyl stretch is observed at 1648 cm − 1 [30, 57], while the band at 1620 cm − 1 is attributed to the C = C double bond stretching of the aromatic ring [59–61]. In addition, the peaks at 1490 cm − 1 and 1250 cm − 1 are associated with CH–CH and C–O single bonds, respectively [57, 62]. Peaks at 1098 cm − 1 and 1019 cm − 1 indicate ring vibrational modes and C–O stretching [63, 64]. The bands in the 898 − 678 cm − 1 range are attributed to scissor-like deformations of the aromatic ring's C–H single bond [63, 65]. An absorption band at 1560 cm − 1 corresponds to the NH 2 and NH…NH functional groups of CS. Weak absorptions in the range of 1510–1530 cm − 1 and near 1630 cm − 1 indicate the presence of a protonated amino group in CS [66, 67]. A broad, intense peak in the region of 3000–3600 cm –1 indicates extensive O–H and N–H stretching in the PVA–CS–mangiferin nanofibers. In the spectra of nanofibers, a strong peak at 1705 cm –1 corresponds to C = O stretching[68], while the disappearance of the 1264 cm –1 peak (C–O bond[69] in the carboxyl group of acetic acid) confirms complete solvent removal. The band at 1089 cm –1 is attributed to asymmetric C–O vibrations of the acetate group, and the 844 cm –1 band is associated with the C–H bond vibrations [70, 71]. In the 600–1800 cm –1 region, the sharp peaks characteristic of mangiferin are replaced by broader bands with fewer peaks, indicating a close association between mangiferin and the polymer matrix. 3.4.2. X–ray diffraction (XRD) analysis The X-ray diffraction analysis confirmed the incorporation of mangiferin into the PVA–CS nanofiber matrix. In addition to the characteristic crystalline peaks of PVA and CS, two new peaks at 2θ of 10.6 and 21.2°were observed, with intensity increasing alongside higher mangiferin content, see Fig. 5 . Analysis of the resulting polymer materials showed that increasing mangiferin loading led to a slight decrease in overall crystallinity and an increase in cell size (Table 6 ). Table 6 The PVA–CS–mangiferin nanofiber lattice parameters Lattice parameters Axial Lengths [Å] Angles [°] Cell volume [Å 3 ] Crystallinity (%) a b c α β γ CS powder 15.7371 8.3352 3.0609 90 90 90 401.50 48.29 PVA powder 15.2596 5.2416 9.7092 90 97.188 90 770.48 57.69 PVA – CS 12.7499 7.2561 8.637 90 92.457 90 798.31 57.45 PVA – CS – 0.5% mangiferin 16.2405 5.5343 9.4481 90 92.659 90 848.28 56.59 PVA – CS – 1.0% mangiferin 16.4884 9.7364 5.427 90 93.51 90 869.60 53.21 The incorporation of mangiferin into the PVA–CS nanofibers altered the crystal structure, affecting both the lattice parameters and overall crystallinity. These changes are expected to influence the mechanical, thermal, and drug release properties of the nanofiber matrix. 3.4.3. PVA – CS – mangiferin nanofiber thermal analysis a. Differential scanning calorimetry (DSC) analysis Figure 6 presents the DSC heating curves of PVA–CS–mangiferin nanofibers at various mangiferin concentrations. Table 7 DSC results for the thermal desorption of PVA – CS – mangiferin nanofibers. Sample ΔH PVA (J/g) χ PVA (%) ΔH CS (J/g) T g (°C) T m (°C) CS powder – – 7.35 – 268 PVA powder 86.01 57.34 – 68 225 PVA – CS 38.72 25.81 13.82 73 222; 251 PVA – CS – 0.5% mangiferin 38.03 25.35 11.47 78 215; 248 PVA – CS – 1.0% mangiferin 40.05 26.70 7.46 78 214; 247 According to the statistical findings in Table 7 , the integration of mangiferin significantly alters the thermal characteristics of nanofibers, resulting in a 10°C decrease in melting temperature and a 5°C increase in glass transition temperature. These shifts in thermal behavior indicate that mangiferin effectively modifies the polymer matrix, supporting its suitability as a therapeutic substance in PVA–CS nanofiber systems. 3.4.4. Thermogravimetric analysis (TGA) TGA curves of heating PVA powder, CS powder, PVA–CS nanofibers, PVA–CS–mangiferin film, and PVA–CS–mangiferin nanofibers at different concentrations of mangiferin are shown in Fig. 7 . Similar to PVA powder and PVA–CS nanofibers, the thermal decomposition of PVA–CS–mangiferin composites proceeds in 3 stages, Table 8 . Table 8 Stages of thermal decomposition and weight reduction of polymer powder and nanofiber samples. Degradation stages PVA powder CS powder PVA–CS nanofiber PVA – CS – 0.5% mangiferin nanofiber PVA – CS – 1.0% mangiferin nanofiber PVA – CS – 0.5% mangiferin film First stage Range ( о С) 25–202 25–177 25–172 25–172 25–172 25–172 Peaks ( o C) 112 67 52; 107 52; 112 53; 113 41; 107 Weight loss (%) 3.04 5.21 8.58 8.44 10.16 23.01 Second stage Range ( о С) 202–367 177–462 172–377 172–377 172–377 172–377 Peaks ( o C) 297 302 267 277; 332 282; 337 298 Weight loss (%) 83.37 77.04 61.40 64.36 57.50 42.76 Third stage Range ( о С) 367–527 377–547 377–547 377–547 377–547 Peaks ( o C) 422; 442; 462 422; 437; 457 442 437 442 Weight loss (%) 10.32 16.97 15.39 15.47 15.72 The PVA–CS–mangiferin film exhibits a higher content of accumulated water and a higher decomposition temperature than the nanofiber samples. During the second stage of thermal decomposition, increasing mangiferin content shifts the primary peaks from 267°С to 277°С and 282°С, with new secondary peaks emerging at 332 and 337°С. For the PVA–CS–mangiferin film, the main peak occurs at 298°C, with the secondary peak appearing as a shoulder. In general, the main decomposition peaks of the PVA–CS nanofiber matrix, with or without mangiferin, are lower than those for individual polymers. This demonstrates that the interactions within the composite are fragile, such as hydrogen bonds or Van der Waals forces. 3.4.5. Tensile property PVA–CS nanofiber matrices with varying amounts of mangiferin were tested for their tensile properties in both vertical and horizontal orientations (Table 9 , Figs. 8 and S6) Table 9 Parameters of tensile properties of PVA – CS – mangiferin nanofibers C Mangiferin (%) Tensile strength [MPa] Elongation at Break [%] Young's modulus [MPa] Horizontal Vertical Horizontal Horizontal Vertical Horizontal 0 7.916 ± 0.970 4.912 ± 0.965 13.07 ± 0.53 16.40 ± 0.82 546.113 ± 32.150 333.086 ± 23.851 0.5 5.005 ± 0.754 3.043 ± 0.755 13.13 ± 0.88 15.20 ± 0.43 470.380 ± 18.770 342.273 ± 18.746 1.0 4.758 ± 0.618 1.406 ± 0.439 10.29 ± 0.80 9.48 ± 2.71 411.089 ± 192.751 257.609 ± 18.391 The presence of microheterogeneous structures significantly impacts the physical and mechanical characteristics of PVA–CS–mangiferin nanofibers. As the mangiferin content increases, the ultimate tensile strength decreases regardless of the deformation axis. For nanofibers oriented in the direction of the deformation axis, tensile strength increases by 50–60%, elongation at break decreases by 10–20% on average, and the elastic modulus decreases by 20–25% (see Table 9 and Figs. 8 and S6). 3.4.4. Drug release from PVA–CS–mangiferin nanofiber matrices To evaluate the release of biologically active substances, 5 mg aliquots of PVA–CS–mangiferin nanofibers were immersed in 10 ml of distilled water (pH = 6.2) for 12 hours, a duration considered optimal for establishing equilibrium. UV spectral analysis of the resulting solutions, recorded in the 200–400 nm range, is presented in Fig. 9 . Given the solubility of polymers and the low solubility of mangiferin, it remains unclear whether mangiferin is released as a free compound or within the polymer matrix. To address this, aqueous solutions were analyzed after 12 hours of release for the presence of polymers. IR spectroscopy was used to correlate the absorption band intensities of PVA, CS, and mangiferin (see Fig. 10 and Table 10 ). Table 10 Determination of the presence of polymers in an aqueous solution after 12 hours Sample Initial spectra Proportion ± standard deviation PVA-CS-mangiferin ratio PVA CS Mangiferin Fiber with 1% mangiferin Powder spectra 3,3757 ± 0,0361 0,0961 ± 0,0189 0,0157 ± 0,0062 ~ 225:62:1 Analysis showed that both PVA and CS were present in the solution after immersion of nanofibers, with PVA detected in significantly exceeded proportions than CS. The release of mangiferin was further evaluated in buffer (pH 7.4, 37°C) using nanofiber matrices obtained from solutions containing 4% PVA, 3% CS, and varying mangiferin concentrations (0.01%, 0.1%, 0.5% and 1.0%). The resulting nanofibers contained 0.14%, 1.41%, 6.67%, and 12.5% mangiferin, respectively. Figure 11 displays the mangiferin release profiles as determined by high-performance liquid chromatography (HPLC). The release study in buffer (pH = 7.4) showed that nanofibers containing 6.67% mangiferin exhibited greater drug release compared to those with 12.5% mangiferin. Notably, the release profile was characterized by an initial burst release, a phenomenon commonly observed in similar polymer systems. Additionally, the effect of prolonged storage was investigated by keeping nanofibers in aqueous solutions for 4 months. As shown in Figures S7, S8, and S9, IR spectroscopy revealed that, over time, stronger intermolecular hydrogen bonds formed between the mangiferin and the PVA–CS polymer matrix, particularly involving the phenolic hydroxyl at C 6 and C 3 (structure II and structure I, Fig S1 ). After 4 months of storage, no change was observed in the position of the absorption bands at 25 ° C and 5 o C, indicating structural stability of the nanofibers. In summary, mangiferin can be incorporated into nanofibers at concentrations 5–10 times higher than its solubility, without altering its chemical structure. The interaction between mangiferin and the polymer systems is mainly through hydrogen bonding. Variations in mangiferin proportion affect the crystallinity and lattice structure, leading to changes in the thermal and mechanical properties of the nanofibers. Especially, nanofibers containing 6.67% mangiferin exhibited rapid drug release under acidic conditions typical of diseased cells and slow release at neutral pH, corresponding to healthy cells. The integration of mangiferin into PVA–CS nanofibrous materials using an acetic acid-water-ethanol solvent system enhances both bioavailability and the loading capacity of biologically active substances, up to 12.25%. 4. Conclusion This study presents, for the first time, the fabrication of mangiferin-loaded nanofibers based on PVA and CS and using a ternary acetic acid-water-ethanol solvent system. This approach offers a promising strategy for the development of polymer-based drug delivery systems designed to enhance the bioavailability of compounds with inherently low solubility. Key findings on mangiferin incorporation in PVA–CS nanofiber system: • Mangiferin can be integrated into a nanofiber at concentrations 5–10 times higher than its solubility. The optimal electrospinning solution comprises 4 % PVA, 3 % CS, 0.5 % mangiferin, 45 % CH 3 COOH, and 15 % C 2 H 5 OH. • The most effective electrospinning parameters were the needle-collector distance of 150mm, the feed rate of 0.2 mL/h, and the applied voltage of 28 kV, resulting in nanofibers with an average diameter of 332 ± 84 nm. • Mangiferin retains its chemical structure and remains stable in both solution and composite nanofibers for at least 40 days at room temperature. • The interaction between mangiferin and the polymer matrix is primarily through hydrogen bonding, which readily dissociates in the aqueous environments. • Increasing mangiferin content leads to a slight decrease in overall crystallinity and an increase in cell size, thereby modulating the glass transition, melting behavior, thermal decomposition and mechanical properties of the polymer nanofiber systems. These results highlight mangiferin’s suitability as a therapeutic agent in PVA-CS nanofiber matrices. • Electrospun nanofibers can accommodate up to 12.25% drug loading and remain stable in water for up to 4 months, as indicated by unchanged infrared spectra peaks. • Nanofibers containing 6.67%, prepared from a solution containing 0.5% mangiferin, exhibited optimal preserved mechanical properties and intact drug release capability, indicating this formulation as the most favorable for therapeutic applications within the PVA–CS–mangiferin nanofiber system. Declarations The authors have no financial or proprietary interests in any material discussed in this article. Author Contribution Thi Hong Nhung Vu: investigation, data curation, formal analysis, original draft. Svetlana N. Morozkina: validation, resources, review, and editing. Vera E. Sitnikova: data curation, methodology. Yuliya E. Generalova: data curation, methodology. Nguyen Quang Sang : software. Mayya V. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8759759","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":614443195,"identity":"2295081d-62f5-4b99-a265-c51c0031430c","order_by":0,"name":"Thi Hong Nhung Vu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5klEQVRIiWNgGAWjYFACHjCZACY/ADEbOylaGGeAtDCTooUZzCakxeBG7sHHBb/u5Bncbr/82ebXNnk+ZgbGDx9z8GnJSzae2fes2ODOmTLp3L7bhm3MDMySM7fh1iI5I8dMmrfncOKGGzlpzLk9txmBWtiYeYnUkvzZsue2PUEt/BJALTw/QFrSD0gz/LidSFgLzxtjY96Gw4kzb+SwSfY23E5uY2ZsxusXNvYcw8c8fw4n9t1If/zhx5/btvPbmw9++IhHCxgwtoFIHgMog7GBgHoQ+AMi2B9AGaNgFIyCUTAKUAEAHlZVGa2ICOIAAAAASUVORK5CYII=","orcid":"","institution":"Vietnam National University of Forestry at Dong Nai","correspondingAuthor":true,"prefix":"","firstName":"Thi","middleName":"Hong Nhung","lastName":"Vu","suffix":""},{"id":614443196,"identity":"63724d00-7bb5-4c5a-881e-002e52c1b71c","order_by":1,"name":"Svetlana N. Morozkina","email":"","orcid":"","institution":"Saint Petersburg State University","correspondingAuthor":false,"prefix":"","firstName":"Svetlana","middleName":"N.","lastName":"Morozkina","suffix":""},{"id":614443197,"identity":"8aaeaa38-a6e5-46cf-adf8-c4c550b445a9","order_by":2,"name":"Vera E. Sitnikova","email":"","orcid":"","institution":"ITMO University","correspondingAuthor":false,"prefix":"","firstName":"Vera","middleName":"E.","lastName":"Sitnikova","suffix":""},{"id":614443198,"identity":"a0afa5e2-fdf1-4374-a6b3-0fed54640dc1","order_by":3,"name":"Yuliya Е. Generalova","email":"","orcid":"","institution":"Saint - Petersburg State Chemical Pharmaceutical Academy","correspondingAuthor":false,"prefix":"","firstName":"Yuliya","middleName":"Е.","lastName":"Generalova","suffix":""},{"id":614443199,"identity":"56ffe6c1-49f5-473a-a86a-5c60e96c8ab0","order_by":4,"name":"Quang Sang Nguyen","email":"","orcid":"","institution":"Nam Can Tho University","correspondingAuthor":false,"prefix":"","firstName":"Quang","middleName":"Sang","lastName":"Nguyen","suffix":""},{"id":614443200,"identity":"60944d6a-cf7f-4a77-acc0-0a67fd26d87e","order_by":5,"name":"Mayya V. Uspenskaya","email":"","orcid":"","institution":"Saint Petersburg State University","correspondingAuthor":false,"prefix":"","firstName":"Mayya","middleName":"V.","lastName":"Uspenskaya","suffix":""}],"badges":[],"createdAt":"2026-02-02 02:53:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8759759/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8759759/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105847423,"identity":"302280c3-0d68-4044-8f17-c981edbf97cd","added_by":"auto","created_at":"2026-03-31 18:15:33","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":465315,"visible":true,"origin":"","legend":"\u003cp\u003eMolecular structure of mangiferin\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8759759/v1/ea9a16f92df02794435fba9a.png"},{"id":105905327,"identity":"4d7f4c71-195a-4267-bd84-7e43dc26d432","added_by":"auto","created_at":"2026-04-01 10:11:50","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":603893,"visible":true,"origin":"","legend":"\u003cp\u003eUV-Vis spectra of mangiferin solutions in distilled water, 60% ethanol, and a mixed solvent of 15% ethanol-45% acetic acid\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8759759/v1/54372014fadd0d1edba0a86b.png"},{"id":105847430,"identity":"4c4a0fa0-7d4a-4838-bf90-3ff42bfbe382","added_by":"auto","created_at":"2026-03-31 18:15:33","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1039333,"visible":true,"origin":"","legend":"\u003cp\u003eUV-Vis spectra of mangiferin solution and PVA–CS–mangiferin solutions in mixed solvent water-ethanol-acetic acid\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-8759759/v1/b60ece9efed123f7a8e58fd8.png"},{"id":105847425,"identity":"c64f9a83-2df3-41c3-8f91-d45b5212bae6","added_by":"auto","created_at":"2026-03-31 18:15:33","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":725081,"visible":true,"origin":"","legend":"\u003cp\u003eInfrared spectra of PVA–CS–mangiferin nanofibers.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-8759759/v1/b467240622d4adf9a6c2d937.png"},{"id":105847426,"identity":"1ed7ecf0-2b5f-49fb-899c-7e91b8f9e244","added_by":"auto","created_at":"2026-03-31 18:15:33","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":150303,"visible":true,"origin":"","legend":"\u003cp\u003eX–Ray diffraction of PVA powder, CS powder, PVA nanofiber, PVA – CS nanofiber and PVA – CS – mangiferin nanofibers\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-8759759/v1/3dc408e89271143453f6da2f.png"},{"id":105847428,"identity":"521416df-8c04-492d-b100-5c9b464b6065","added_by":"auto","created_at":"2026-03-31 18:15:33","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":582581,"visible":true,"origin":"","legend":"\u003cp\u003eDSC heating curve of PVA powder, CS powder, PVA–CS nanofiber, and PVA–CS–mangiferin nanofibers\u003c/p\u003e","description":"","filename":"Figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-8759759/v1/1a5c8ceb0a3cc41efc3dd83c.png"},{"id":105904466,"identity":"69233367-412c-4bd4-add9-98c775ba2004","added_by":"auto","created_at":"2026-04-01 10:08:49","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":502484,"visible":true,"origin":"","legend":"\u003cp\u003eTGA thermogram of \u0026nbsp;PVA powder, CS powder, PVA–CS nanofiber, PVA–CS–mangiferin film, and PVA–CS–mangiferin nanofibers\u003c/p\u003e","description":"","filename":"Figure7.png","url":"https://assets-eu.researchsquare.com/files/rs-8759759/v1/640842f9082da1f14822a9ab.png"},{"id":105847429,"identity":"cd2dcdf9-80cb-4a9b-8e19-808252b20c64","added_by":"auto","created_at":"2026-03-31 18:15:33","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":297147,"visible":true,"origin":"","legend":"\u003cp\u003eThe deformation of PVA – CS – mangiferin nanofibers\u003c/p\u003e","description":"","filename":"Figure8.png","url":"https://assets-eu.researchsquare.com/files/rs-8759759/v1/27c09ef4fbff0cf5aeaa3433.png"},{"id":105847433,"identity":"2f26cfed-2fdd-4632-a573-38492673b528","added_by":"auto","created_at":"2026-03-31 18:15:33","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":405898,"visible":true,"origin":"","legend":"\u003cp\u003eUV-Vis spectra of aqueoussolutions of mangiferin and PVA–CS–mangiferin nanofibers.\u003c/p\u003e","description":"","filename":"Figure9.png","url":"https://assets-eu.researchsquare.com/files/rs-8759759/v1/ef4b21f40fbe74450b4e71f4.png"},{"id":105847431,"identity":"744243b5-5f59-42c8-ab04-7699707a4a76","added_by":"auto","created_at":"2026-03-31 18:15:33","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":883343,"visible":true,"origin":"","legend":"\u003cp\u003eDetermination of the presence of polymers in an aqueous solution after 12 hours\u003c/p\u003e","description":"","filename":"Figure10.png","url":"https://assets-eu.researchsquare.com/files/rs-8759759/v1/6304b1492cd9578db7672962.png"},{"id":105847432,"identity":"396bf4cd-b965-496b-9b5c-3f2fbe78a70c","added_by":"auto","created_at":"2026-03-31 18:15:33","extension":"png","order_by":11,"title":"Figure 11","display":"","copyAsset":false,"role":"figure","size":355209,"visible":true,"origin":"","legend":"\u003cp\u003eRelease of mangiferin from polymer fibers in pH 7.4 buffer at 37 degrees\u003c/p\u003e","description":"","filename":"Figure11.png","url":"https://assets-eu.researchsquare.com/files/rs-8759759/v1/910b79ea37efc79785678c5f.png"},{"id":106401662,"identity":"d2ff1b61-f5b1-4666-b675-27960466bce8","added_by":"auto","created_at":"2026-04-08 09:08:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":7325428,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8759759/v1/385fa1bc-bb1b-4356-a188-17e129756d82.pdf"},{"id":105847422,"identity":"b901ac1d-721a-4f69-8e12-dff8b14f27d5","added_by":"auto","created_at":"2026-03-31 18:15:33","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":10678703,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryInformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-8759759/v1/c94e11c83346d482ebbba41e.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Electrospun poly(vinyl alcohol)-chitosan nanofibers integrated with mangiferin: fabrication and properties","fulltext":[{"header":"Highlights","content":"\u003cp\u003e\u0026bull; The electrospinning solution can carry 5\u0026ndash;10 times more mangiferin than its solubility.\u003c/p\u003e\u003cp\u003e\u0026bull; Mangiferin was stable in the electrospinning solution after 40 days at room temperature.\u003c/p\u003e\u003cp\u003e\u0026bull; Determined the optimal strategy for producing mangiferin-blended PVA-CS nanofibers;\u003c/p\u003e\u003cp\u003e\u0026bull; Electrospun nanofibers can contain up to 12.25% medication.\u003c/p\u003e\u003cp\u003e\u0026bull; Electrospun nanofibers can be stored in water for up to 4 months.\u003c/p\u003e"},{"header":"1. Introduction","content":"\u003cp\u003eIn the context of personalized medicine, the most urgent challenge is developing drug delivery systems that incorporate biologically active substances, particularly antioxidants, due to their broad therapeutic potential in treating gastrointestinal disorders, diabetes, and cancers. Importantly, diseased and healthy differ in both their characteristics and microenvironment; while healthy typically maintain a neutral or slightly extracellular pH of 7.1\u0026ndash;7.4 [1, 2], diseased cells generally exhibit a more acidic microenvironment. In inflammatory conditions such as tumors, the extracellular pH becomes increasingly acidic, ranging from 7.2 to 6.5, and can decrease to 5.4 within tissues. Similarly, myocardial ischemia and hematomas associated with fractures exhibit pH values of 5.7 and 4.7, respectively [1, 3]. Another key distinction between abnormal (particularly cancerous) and healthy cells is their metabolic pathway: cancer cells convert glucose to lactic acid rather than CO\u003csub\u003e2\u003c/sub\u003e and water (Warburg effect, 1956)[1, 4], resulting in an acidic, negatively charged microenvironment with elevated lactate ion concentration. Cancer cells preferentially utilize glucoside molecules for proliferation [4, 5], making them more likely to absorb molecules with basic, positively charged, and glycoside structures. These properties can be leveraged for targeted drug delivery, as such compounds are selectively taken up by diseased cells. Additionally, molecules with antioxidant activity and functional groups such as alcohol, phenol, carbonyl, and conjugated π-bonding systems can inhibit disease progression and support cellular recovery.\u003c/p\u003e \u003cp\u003eMangiferin is broadly distributed among plant species, particularly within the \u003cem\u003eAnacardiaceae\u003c/em\u003e and \u003cem\u003eGentianaceae\u003c/em\u003e families [6]. Mangiferin can be extracted from multiple plant parts, including leaves, bark, stem, fruit peel, and roots, and is recognized as one of the most potent naturally occurring antioxidants [7\u0026ndash;10]. Among dietary sources, honeybush tea (\u003cem\u003eCyclopia sp\u003c/em\u003e.) in South Africa is particularly notable, with dried leaves containing up to 4% mangiferin by weight [10]. Since its initial isolation from mangoes (\u003cem\u003eMangifera indica L\u003c/em\u003e., \u003cem\u003eAnacardiaceae\u003c/em\u003e) in 1908, extensive research has elucidated its composition, structure, and properties. Mangiferin is classified as a xanthonoid, specifically norathyriol glucoside [7, 8].\u003c/p\u003e \u003cp\u003eMangiferin, the molecular structure of which is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, comprises eight hydroxyl groups: four located within the glucopyranosyl moiety and four others directly bonded to the xanthone skeleton. The hydroxyl groups associated with the glucopyranosyl unit exhibit comparatively lower acidity than those attached to the xanthone scaffold. Specifically, the hydroxyl groups at positions C\u003csub\u003e1\u003c/sub\u003e, C\u003csub\u003e3\u003c/sub\u003e, C\u003csub\u003e6\u003c/sub\u003e, and C\u003csub\u003e7\u003c/sub\u003e are expected to display enhanced acidity, as previously reported [11, 12]. Owing to the formation of a condensed ring system, rotational freedom around the C\u0026ndash;C bonds is restricted. The structure elucidation of mangiferin was achieved in the 1960s [7, 13], revealing its classification as a polyphenolic compound covalently linked to a glucose residue via a C\u0026ndash;C bond.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eMangiferin has demonstrated significant therapeutic potential across a broad spectrum of pathological conditions. Traditionally used in ethnomedicine, mangiferin-rich plants have been applied in the management of cardiovascular disease, infections, hypoglycemia, burns, liver disease, and cancers [7, 10, 14, 15]. Extensive pharmacological investigations have revealed that mangiferin possesses a diverse array of bioactivities, including analgesic, antidiabetic, antisclerotic, antimicrobial, antiviral, cardioprotective, hepatoprotective, neuroprotective, anti-inflammatory, and antiallergic effects [14, 16]. Notably, mangiferin inhibits antiviral efficacy against several clinically relevant viruses. It has been shown to inhibit the replication of influenza viruses [17], herpes simplex type I [18], herpes, and lifelong infections [19]. Furthermore, mangiferin effectively suppresses HIV-1 replication in a dose-dependent manner [17], and has been identified as a promising candidate for treating poliovirus infections [20]. Beyond its antiviral properties, mangiferin also exerts additional biological effects, including analgesic, antipyretic, gastroprotective, anti-cryptosporidium, anti-allergic, and radioprotective activities [21].\u003c/p\u003e \u003cp\u003eNumerous \u003cem\u003ein vitro\u003c/em\u003e and \u003cem\u003ein vivo\u003c/em\u003e studies have consistently demonstrated the potent biological activities of mangiferin. However, despite its promising pharmacological potential, mangiferin has not garnered sufficient scientific or clinical attention. This limited interest is primarily attributed to its poor oral bioavailability and low aqueous solubility[22, 23]. Mangiferin exhibits limited solubility in ethanol, is marginally soluble in water (0.111 mg/mL) [23], and is practically insoluble in non-polar solvents, such as n-hexane and diethyl ether [24]. The oral bioavailability of mangiferin is reported to be approximately 1.2% [25]. This limitation could be attributed to mangiferin's low lipophilic features, poor intestinal membrane permeability, and limited oral absorption [26]. These pharmacokinetic drawbacks significantly hinder the clinical translation and therapeutic application of mangiferin. Consequently, only a limited number of mangiferin-based products are currently available on the market. Among them, the most recognized is Vimang, a phytopharmaceutical derived from the aqueous extract of \u003cem\u003eMangifera indica\u003c/em\u003e containing approximately 20% mangiferin [27]. Vimang is commercially formulated as tablets, creams, and syrups, and is primarily used in the supportive treatment of various cancer types [6].\u003c/p\u003e \u003cp\u003eThe therapeutic impact of mangiferin is constrained by its extremely poor oral bioavailability. To address this limitation, encapsulation within natural polymeric matrices has been explored as a strategy to enhance its loading capacity, controlled release, and systemic bioavailability. Typically, the complexes mangiferin\u0026ndash;phospholipid and mangiferin\u0026ndash;phospholipid\u0026ndash;polysorbate-80[28, 29] have demonstrated improved solubility profiles. Similarly, formulations incorporating mangiferin with pluronic F127, pluronic P123, vitamin E, and TPGS[30] have yielded favorable solubilization outcomes. Mangiferin-hyaluronic acid (HA) nanoparticles exhibited droplet sizes ranging from 194.5 to 397.9 nm, with a negative zeta potential (\u0026lt;-30 mV) and maintained physical stability up to 30 days at 4\u0026deg;C. Nanoparticles formulated with short-chain HA nanoparticles (40\u0026ndash;50 kDa) presented reduced particle size, enhanced negative surface charge, and a 2.5-fold increase in permeability compared to unformulated mangiferin (Q\u003csub\u003e24\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;5.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01 \u0026micro;g/cm\u003csup\u003e2\u003c/sup\u003e). Furthermore, the combination of transcutola-P resulted in a 5-fold enhancement in permeability (Q\u003csub\u003e24\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;9.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01 \u0026micro;g/cm\u003csup\u003e2\u003c/sup\u003e) [29]. Besides, the incorporation of mangiferin into an ethylene vinyl acetate copolymer containing sorbitol ether (Span\u0026reg;20) resulted in a marked enhancement of the polymer film's antioxidant activity up to 80% [31]. Additionally, polylactic acid-mangiferin nanoparticles produced by emulsion solvent evaporation revealed antiproliferative activity in vitro on BEAS 2B and HEPG2. These nanoparticles exhibited resistance to gastrointestinal digestion for up to 1.5 hours and did not adversely affect the metabolism or biological activity of healthy cells [32]. In addition, mangiferin-loaded carrageenan/CS core-shell hydrogel beads displayed a delayed and sustained release profile for mangiferin, while maintaining non-toxicity and supporting high cell viability[33]. Preliminary swelling and \u003cem\u003ein vitro\u003c/em\u003e release studies identified polyvinyl alcohol, CS, and gelatin hydrogels as the most suitable matrices for controlled mangiferin release in aqueous media at pH values of 5.5 and 10.0 [34].\u003c/p\u003e \u003cp\u003eMost existing studies have focused on the development and characterization of polymer nanoparticles encapsulating mangiferin [35]. In contrast, research on polymer fibers incorporating mangiferin remains scarce. To address this gap, the present study investigates the integration of mangiferin into PVA and CS nanofibers. PVA and CS were selected as the primary matrix materials due to their biosafety, physiological activity, extensive biomedical applications, and abundant availability[36,37]. PVA is a hydrophilic polymer with a poly alcohol structure, enabling hydrogen bonding and excellent water solubility. These properties make PVA an effective carrier for poorly water-soluble compounds such as mangiferin. Given that water constitutes 55% to 78% of the human body, depending on age and gender, with making up 31% of bones, 73% of the heart and brain, 79% of muscles and kidneys, and 83% of the lungs [36]. As a result, the use of water-soluble polymers facilitates systemic distribution, except in adipose tissues. PVA is widely recognized for its abundance, non-toxicity, biosafety, and high biocompatibility [37\u0026ndash;42]. Consequently, it is extensively applied in biomedical fields, including eye drops, contact lenses, ocular inserts, ocular films, nanoparticles, microspheres, floating microspheres, mucoadhesive, targeted drug delivery systems, soft tissue, articular cartilage, intervertebral disc nucleus, artificial skin, and vocal cords,... [37, 43].\u003c/p\u003e \u003cp\u003eThe chemical structure of CS makes it an excellent candidate for targeted drug delivery systems [46]. Its polysaccharide backbone, combined with basic and positively charged amine functional groups [44, 45], enhances its affinity for diseased cells. Due to its solubility in acidic media and insolubility in neutral and basic environments, CS enables both targeted drug delivery and controlled drug release at the intended site. Numerous studies have demonstrated that CS is safe, non-toxic, biodegradable, and biocompatible [45, 46], and it exhibits beneficial biological activities, including antibacterial, antioxidant, and anti-inflammatory effects [44, 45, 47, 48]. Consequently, CS is widely used in food and medical applications, including orthopedics and periodontics, drug delivery systems, wound healing, and tissue engineering [49].\u003c/p\u003e \u003cp\u003eThe incorporation of mangiferin, as the active pharmaceutical ingredient, PVA as the delivery matrix, and CS as the directional material presents a promising strategy for targeted drug delivery system design. This study provides a comprehensive investigation into the electrospinning fabrication of PVA-CS-mangiferin nanofibers, with detailed analysis of solution composition, processing parameters, fiber morphology, and the resulting physicochemical properties.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Materials\u003c/h2\u003e \u003cp\u003ePVA (molecular weight: ~ 75 kDa, GOST TU: GOST 10779-78) and CS ( molecular weight: 200 kDa, TU 9289-067-00472124-03) were used to fabricate PVA-CS nanofibers for mangiferin incorporation. Mangiferin (C\u003csub\u003e19\u003c/sub\u003eH\u003csub\u003e18\u003c/sub\u003eO\u003csub\u003e11\u003c/sub\u003e, CAS No 4773-96-0, molecular weight 422.37, purity 98%) was purchased from Gute Chemie-abcr. The solvent system consisted of distilled water, acetic acid (99.5%), and ethanol (98%).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. UV-Vis spectroscopy analysis\u003c/h2\u003e \u003cp\u003eThe presence and release of mangiferin in solutions and from nanofiber matrices were evaluated using a UNICO UV/Vis spectrophotometer (USA) with a wavelength range of 190\u0026ndash;1100nm, and a resolution of 1 nm.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Electrospinning Technique\u003c/h2\u003e \u003cp\u003eElectrospun nanofibers were fabricated using a NANON-01A electrospinning system (MECC CO., LTD., Fukuoka, Japan). The process was conducted at 28.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u0026deg;C and 21\u0026thinsp;\u0026plusmn;\u0026thinsp;3% relative humidity. Key parameters were systematically varied, including voltage (16\u0026ndash;30 kV), feed rate ( 0.1\u0026ndash;0.4 mL/h), and needle-to-collector distance (100 mm \u0026ndash; 150 mm). Electrospinning was performed using a 16G steel needle, a horizontal speed of 10 mm/s, and a stainless steel receiver plate (150 mm \u0026times; 200 mm).\u003c/p\u003e \u003cp\u003eThe nanofiber matrices for mechanical and drug release studies were collected from the device's rotating drum at 500 rpm.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Morphology and Diameters of Nanofibers\u003c/h2\u003e \u003cp\u003ePreliminary characterization, morphology, and diameter measurements of electrospun fibers were performed using an Olympus STM6 optical microscope (OLYMPUS Corporation, Tokyo, Japan). The differential interference contrast (DIC) technique was employed to enhance fiber color and contrast. Nanofiber diameters were analyzed using ImageJ software (National Institutes of Health, Bethesda, MD, USA).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5. Fourier-transform infrared (FTIR) spectroscopy\u003c/h2\u003e \u003cp\u003eAttenuated total internal reflection (ATR) FTIR spectra were acquired in the 4000\u0026thinsp;\u0026minus;\u0026thinsp;600 cm\u003csup\u003e\u0026ndash;1\u003c/sup\u003e range using a Bruker Tensor 37 FTIR spectrophotometer equipped with a diamond-coated ZnSe crystal (MIRacle, Pike). Spectra were recorded at a resolution of 2 cm\u003csup\u003e\u0026ndash;1\u003c/sup\u003e, averaging 32 scans.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.6. X\u0026ndash;ray diffraction (XRD) analysis\u003c/h2\u003e \u003cp\u003eWide\u0026ndash;angle X\u0026ndash;ray diffraction (XRD) profiles of PVA powder, CS powder, and nanofibers were obtained at room temperature using a DRON\u0026ndash;8 X\u0026ndash;ray unit equipped with a BSV\u0026ndash;29 sharp confocal tube ( copper anode), a NaI (Tl) detector, and a β-filter (Ni). Flat surface samples were placed on glass slides for analysis. The 2θ range for the samples was 10\u0026ndash;60\u0026deg;. The average crystallite size was calculated using the Scherrer formula:\u003c/p\u003e \u003cp\u003eτ\u0026thinsp;=\u0026thinsp;K λ/β cos θ\u003c/p\u003e \u003cp\u003ewhere τ is the average crystallite size, K is the shape factor (0.98 rad), λ is the X\u0026ndash;ray wavelength (1.54 \u0026Aring;), β is the full width at half maximum (FWHM) of the diffraction peak, and θ is the Bragg angle. The normalized area of the diffraction peaks was used to determine the degree of crystallinity [50].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.7. Differential scanning calorimetry (DSC) analysis\u003c/h2\u003e \u003cp\u003eDifferential scanning calorimetry (DSC) was performed using a DSC 204 F1 Phoenix instrument (Netzsch, Germany). Samples (~\u0026thinsp;2 mg) were analyzed in closed aluminum crucibles under nitrogen flow (protective gas: 80 mL/min, working gas: 30 ml/min) over a temperature range of \u0026ndash; 30\u0026deg;C to 300\u0026deg;C, at a heating/cooling rate of 10 K/min. To remove the adsorbed moisture, samples were heated from room temperature to 150\u0026deg;C. Before analysis, samples were heated to 150\u0026deg;C to remove adsorbed moisture, held for 5 minutes, then cooled to \u0026ndash; 30\u0026deg;C. Air was used as the reference.\u003c/p\u003e \u003cp\u003eThe degree of crystallinity (\u003cem\u003eχ\u003c/em\u003e\u003csub\u003e\u003cem\u003ec\u003c/em\u003e\u003c/sub\u003e) was calculated using the following equation:\u003c/p\u003e \u003cp\u003e \u003cem\u003eχ\u003c/em\u003e \u003csub\u003e \u003cem\u003ec\u003c/em\u003e \u003c/sub\u003e = \u003cem\u003e(∆H\u003c/em\u003e/\u003cem\u003em ∆H\u003c/em\u003e\u003csub\u003e\u003cem\u003eo\u003c/em\u003e\u003c/sub\u003e) \u0026times; 100\u003c/p\u003e \u003cp\u003ewhere \u003cem\u003em\u003c/em\u003e is the polymer mass, \u003cem\u003e∆H\u003c/em\u003e is the enthalpy of sample melting, and \u003cem\u003e∆H\u003c/em\u003e\u003csub\u003e\u003cem\u003eo\u003c/em\u003e\u003c/sub\u003e is the enthalpy of fusion of 100% crystalline PVA (150 J/g) [51].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e2.8. Thermogravimetric analysis (TGA)\u003c/h2\u003e \u003cp\u003eThe thermal properties of the initial components and the resulting nanofibers were evaluated using a TG 209 F1 Libra thermogravimetric analyser (Netzsch, Germany). Analyses were conducted over a temperature range of 25\u0026deg;C to 900\u0026deg;C at a heating rate of 10\u0026deg;C/min under a nitrogen atmosphere (gas flow: 40 mL/min), using Al\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e crucibles.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e2.9. Tensile property\u003c/h2\u003e \u003cp\u003eTensile properties were evaluated using an Instron 5943 tensile testing machine (Instron, USA) at room temperature and crosshead speed of 50 mm/min in accordance with ISO 527-3 standards [52].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e2.10. High Performance Liquid Chromatography (HPLC)\u003c/h2\u003e \u003cp\u003eMangiferin release was analyzed using a Shimadzu LC-10 UV detector (Shimadzu, Japan) and a Millichrome-A02liquid chromatograph equipped with an ultraviolet detector (OOO IH \"EkoNova\", Russia). Chromatographic separation was performed on a Waters SunFire C18 column (3.5 \u0026micro;m, 3.0\u0026times;150 mm). The mobile phase consisted of 0.1% phosphoric acid and acetonitrile (85:15 v/v) at a flow rate of 0.4 mL/min. The injection volume was 20 \u0026micro;L, and the column temperature was maintained at 37\u003csup\u003e\u0026deg;\u003c/sup\u003eC.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e2.11. Statistical Analysis\u003c/h2\u003e \u003cp\u003eNanofiber diameter distributions were analyzed from micrographs using OriginPro 2019b (OriginLab Corporation, Northampton, MA, USA). Lattice parameters of polymer powders and nanofibers were determined by analyzing DSC and XRD data with OriginPro 2019b, and X'Pert Highscore software (PANalytical, 2009) with the DICVOL04 indexing program.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results and Discussion","content":"\u003cp\u003eAll concentrations used in this study were expressed as a percentage of weight (%, wt./wt.) and simply denoted as %. Solutions of 4% PVA, 3% CS, 15% ethanol, and 45% acetic acid with various concentrations of mangiferin were prepared on a magnetic stirrer at 90\u0026deg;C.\u003c/p\u003e\n\u003ch3\u003e\u003c/h3\u003e\n\u003cdiv class=\"Heading\"\u003e\u003cb\u003e3. 1. Mangiferin solutions\u003c/b\u003e\u003c/div\u003e \u003cp\u003eThere are limited investigations on the physicochemical behavior of mangiferin in solutions and its interactions with polymer matrices[11].\u003c/p\u003e \u003cp\u003eCarrier polymers capable of non-covalent interactions, such as CS, can form inclusion complexes with hydrophobic bioactive substances, thereby enhancing their solubility in biological fluids. Mangiferin has eight hydroxyl groups: four are directly affixed to the xanthone skeleton, and four are located in the glucopyranosyl system. The fused ring structure restricts the free rotation of the C-C bonds. The hydroxyl functions act as both hydrogen bond donors and acceptors, resulting in stable hydrogen bonding throughout the crystallization of water molecules [53].\u003c/p\u003e \u003cp\u003eMangiferin exhibits pH-dependent behavior; for example[11], a mangiferin solution in DMSO-water (80\u0026thinsp;\u0026minus;\u0026thinsp;20) has a pH of 4.2 [11]. At pH about 7.0, the C\u003csub\u003e6\u003c/sub\u003e hydroxyl group is deprotonated first, followed by C\u003csub\u003e7\u003c/sub\u003e, and at pH 8.2, C\u003csub\u003e3\u003c/sub\u003e is deprotonated (see Fig. \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). The formation of an intramolecular hydrogen bond between C\u003csub\u003e1\u003c/sub\u003e-OH and the keto group was confirmed by NMR. Upon addition of alkali, the hydroxy groups in ring B are primarily affected, while C\u003csub\u003e1\u003c/sub\u003e-OH remains largely unchanged. pH changes also induce bathochromic shifts in the UV spectra [11]. [11]\u003c/p\u003e \u003cp\u003e[11]\u003cem\u003ea. UV-Vis spectral changes of mangiferin in solvents\u003c/em\u003e\u003c/p\u003e \u003cp\u003eThree solutions comprising 0.001% mangiferin in distilled water, a solvent of 60% ethanol, and a combined solvent of 15% ethanol-45% acetic acid were prepared. UV-Vis spectral alterations of these solutions were recorded at the wavelength range of 200\u0026ndash;400 nm at 25\u003csup\u003e\u0026deg;\u003c/sup\u003eC (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAbsorption of UV light in the 200\u0026ndash;400 nm range promotes electrons from ground state orbitals to higher energy orbitals, specifically from the highest occupied molecular orbital (HOMO) to the lowest unoccupied molecular orbital (LUMO) [54]. The addition of ethanol and acetic acid to the mangiferin solution results in a hypsochromic shift (shift to lower wavelengths) and increased absorption. This effect is attributed to the ability of ethanol, water, and acetic acid to form hydrogen bonds with mangiferin, thereby altering its absorption bands and shifting the energy gap between the two electronic states. Furthermore, as an aromatic chemical, mangiferin exhibits changes in peak intensity and position in response to pH-induced disturbances of its conjugated system [54].\u003c/p\u003e \u003cp\u003eAccording to the Vietnamese Pharmacopoeia, the ultraviolet absorption spectrum of mangiferin ethanol exhibits maximum absorption at 241\u0026thinsp;\u0026plusmn;\u0026thinsp;2 nm, 258\u0026thinsp;\u0026plusmn;\u0026thinsp;2 nm, 316\u0026thinsp;\u0026plusmn;\u0026thinsp;2 nm, and 366\u0026thinsp;\u0026plusmn;\u0026thinsp;3 nm [12].\u003c/p\u003e \u003cp\u003e \u003cem\u003eb. Mangiferin in polymer solutions\u003c/em\u003e \u003c/p\u003e \u003cp\u003eWhile numerous works have explored mangiferin-polymer solutions, most focus on nanoparticle formation rather than nanofiber fabrication, and few investigate the structure interactions between mangiferin and the polymer matrix. For example, Pipattanawarothai et al. [34] reported that in hydrogels composed of PVA, CS, and gelatin loaded with mangiferin, the predominant interactions occurred between mangiferin and the functional groups of PVA macromolecules rather than CS.\u003c/p\u003e \u003cp\u003eTo investigate the loading of mangiferin into the polymer matrices, a system containing 4% PVA, 3% CS, 45% acetic acid, and 15% ethanol was employed. This polymer system was used throughout the entire study.\u003c/p\u003e \u003cp\u003eSolutions of mangiferin and PVA\u0026ndash;CS\u0026ndash;mangiferin were prepared in a ternary solvent system of water, acetic acid, and ethanol, and subjected to UV analysis in the wavelength range from 220 to 400 nm at various time points.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e demonstrates that the characteristic absorption peak of mangiferin at 366 nm remained constant after 40 days, indicating the stability of the polymer system.\u003c/p\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Investigation of mangiferin concentration for integration into nanofibers\u003c/h2\u003e \u003cp\u003eThe possibility of forming fibers from electrospun solutions of PVA\u0026ndash;CS\u0026ndash;mangiferin with the addition of 0.01%, 0.1%, 0.5% and 1% mangiferin in the ternary solvent system was studied. The fabrication of PVA\u0026ndash;CS nanofibers incorporated with mangiferin was systematically investigated under a range of electrospinning parameters. Specifically, the needle\u0026ndash;collector distance was varied between 100 and 150 mm, the feed rate was adjusted from 0.1 to 0.2 mL/h, and the applied voltage ranged from 16 to 30 kV. The results presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarize the influence of mangiferin concentration on the formation and morphology of the resulting nanofibers.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eResults of the formation of PVA\u0026ndash;CS\u0026ndash;mangiferin nanofibers at various concentrations of mangiferin under electrospinning conditions: needle\u0026ndash;electrode distance 100\u0026ndash;150 mm, feed rate 0.1\u0026ndash;0.2 mL/h, voltage 16\u0026ndash;30 kV.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"13\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNeedle\u0026ndash;electrode distance (mm)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFeed rate (mL/h)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMangiferin concentration (% w/w)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"10\" nameend=\"c13\" namest=\"c4\"\u003e \u003cp\u003eVoltage (kV)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"9\" rowspan=\"10\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e 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align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e 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align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"9\" rowspan=\"10\"\u003e \u003cp\u003e140\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e 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align=\"left\" colname=\"c5\"\u003e \u003cp\u003eo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e 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align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"4\" rowspan=\"5\"\u003e 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align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e 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align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e 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align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e 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align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e 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\u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"9\" rowspan=\"10\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"13\" nameend=\"c13\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003e(O) Formation of drops and a few fibers. (o) Formation of nanofibers and a few drops;\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(+) Formation of nanofibers; (*) Formation of fibers, but the process is unstable\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe results presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e demonstrate that the incorporation of mangiferin at concentrations ranging from 0.01% to 0.5% into the electrospinning solution did not adversely affect the fiber formation process. However, when the mangiferin concentration was increased to 1.0% the electrospinning process exhibited instability and complications, suggesting an upper threshold for effective drug loading under the tested conditions. Representative microscopic images and the corresponding diameter distributions of PVA\u0026ndash;CS\u0026ndash;mangiferin nanofibers, electrospun at a needle\u0026ndash;collector distance of 140 mm, a feed rate of 0.2 mL/h, and an applied voltage of 28 kV, are shown in Figure S2 and summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDescription of the diameter of electrospun nanofibers from a solution of 4% PVA\u0026ndash;3% CS\u0026ndash;mangiferin solutions, and electrospinning parameters fixed at the collector-needle distance of 140 mm, the feed rate of 0.2 mL/h, and the voltage of 28 kV.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFiber diameter (nm)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003eMangiferin concentration (% w/w)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e285\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e304\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e334\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e334\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e343\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStandard deviation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e83\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMinimum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e121\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e120\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e137\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e172\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e592\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e647\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e646\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e671\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e681\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAs seen in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, increasing mangiferin concentration to 1.0% resulted in a 40% increase in the average fiber diameters. These results indicate that the addition of mangiferin to the polymer spinning solution has a substantial impact not only on the morphological properties of the resulting nanofibers but also on the overall electrospinning behavior. It is additionally proven that a system consisting of 4% PVA, 3% CS, 0.5% mangiferin, 45% acetic acid, and 15% ethanol is most appropriate for further research.\u003c/p\u003e \u003cp\u003eTo further improve the quality and performance of PVA\u0026ndash;CS\u0026ndash;mangiferin nanofibers, it is essential to optimize the technological parameters of the electrospinning process.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003e3.3. Investigation of electrospinning technological parameters\u003c/h2\u003e \u003cp\u003eA systematic investigation into the optimization of electrospinning parameters for the fabrication of PVA\u0026ndash;CS\u0026ndash;mangiferin nanofibers was conducted. The effects of needle\u0026ndash;collector distance, feed rate, and applied voltage were evaluated to determine their influence on fiber morphology and quality.\u003c/p\u003e \u003cp\u003eThe results demonstrated that increasing the needle\u0026ndash;collector distance from 120 mm to 150 mm, while maintaining a feed rate of 0.2 mL/h and a voltage of 28 kV, resulted in nanofibers with the smallest average diameters and the lowest incidence of defects, as shown in Figure S3 and Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDescription of the diameter of electrospun nanofibers from a solution of 4% PVA\u0026thinsp;\u0026minus;\u0026thinsp;3% CS \u0026ndash; 0.5% mangiferin solutions, and electrospinning parameters at collector-needle distance of 120\u0026ndash;150 mm, feed rate of 0.2 mL/h, and voltage of 28 kV.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFiber diameter (nm)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eCollector \u0026ndash; needle distance (mm)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e120\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e130\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e140\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e401\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e388\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e334\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e332\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStandard deviation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e133\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e119\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e84\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMinimum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e147\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e155\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e137\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e172\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e779\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e735\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e671\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e623\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFurther analysis of feed rate (0.1\u0026ndash;0.4 mL/h) at a fixed distance of 150 mm and voltage of 28 kV revealed that a feed rate of 0.2 mL/h produced the most uniform fibers with minimal defects (Figure S4, Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDescription of the diameter of electrospun nanofibers from a solution of 4% PVA \u0026ndash; 3% CS \u0026ndash; 0.5% mangiferin solutions, and electrospinning parameters at collector-needle distance of 150 mm, feed rate of 0.1\u0026ndash;0.4 mL/h, and voltage of 28 kV.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFiber diameter (nm)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eFeed rate (mL/h)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e350\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e332\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e387\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e415\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStandard deviation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e141\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e120\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMinimum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e163\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e172\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e137\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e185\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e646\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e623\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e809\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e799\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAdditionally, varying the applied voltage between 26 and 30 kV indicated that 28 kV was optimal for achieving consistent fiber morphology and diameter distribution (Figure S5, Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDescription of the diameter of electrospun nanofibers from a solution of 4% PVA\u0026ndash;3% CS \u0026ndash; 0.5% mangiferin solutions, and electrospinning parameters at collector-needle distance of 150 mm, feed rate of 0.2 mL/h, and voltage of 26\u0026ndash;30 kV.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFiber diameter (nm)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003eVoltage (kV)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e383\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e361\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e332\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e361\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e370\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStandard deviation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e130\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e94\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMinimum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e158\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e172\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e148\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e658\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e743\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e623\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e696\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e646\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eCollectively, these findings establish that the optimal electrospinning parameters for producing high-quality PVA\u0026ndash;CS\u0026ndash;mangiferin nanofibers are \u003cem\u003ethe needle-electrode distance of 150 mm, the feed rate of 0.2 ml/h, and the applied voltage of 28 kV.\u003c/em\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003e3.4. Investigation of the properties of nanofibers integrated with mangiferin\u003c/h2\u003e \u003cdiv id=\"Sec19\" class=\"Section3\"\u003e \u003ch2\u003e3.4.1. Fourier-transform infrared (FTIR) spectroscopy\u003c/h2\u003e \u003cp\u003eFTIR spectroscopy was conducted on samples of PVA\u0026ndash;CS\u0026ndash;mangiferin nanofibers with varying mangiferin concentrations. Spectra of pure PVA, CS, and mangiferin powders were also obtained for comparison. The analysis confirmed complete solvent removal from the nanofiber matrix, as evidenced by distinct spectral differences between the solution and the final nanofiber samples. Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e displays the infrared spectra for all initial materials, the solution, and the PVA\u0026ndash;CS\u0026ndash;mangiferin nanofiber mats.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe mangiferin spectrum exhibits a characteristic absorption band at 3365 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e corresponding to phenolic OH stretching [55, 56]. Aliphatic C\u0026ndash;H stretching vibrations from the glucose moiety appear at 2939 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e[30, 57] and 2914 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e [58]. The C\u0026thinsp;=\u0026thinsp;O carbonyl stretch is observed at 1648 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e [30, 57], while the band at 1620 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e is attributed to the C\u0026thinsp;=\u0026thinsp;C double bond stretching of the aromatic ring [59\u0026ndash;61]. In addition, the peaks at 1490 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e and 1250 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e are associated with CH\u0026ndash;CH and C\u0026ndash;O single bonds, respectively [57, 62]. Peaks at 1098 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e and 1019 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e indicate ring vibrational modes and C\u0026ndash;O stretching [63, 64].\u003c/p\u003e \u003cp\u003eThe bands in the 898\u0026thinsp;\u0026minus;\u0026thinsp;678 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e range are attributed to scissor-like deformations of the aromatic ring's C\u0026ndash;H single bond [63, 65]. An absorption band at 1560 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e corresponds to the NH\u003csub\u003e2\u003c/sub\u003e and NH\u0026hellip;NH functional groups of CS. Weak absorptions in the range of 1510\u0026ndash;1530 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e and near 1630 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e indicate the presence of a protonated amino group in CS [66, 67].\u003c/p\u003e \u003cp\u003eA broad, intense peak in the region of 3000\u0026ndash;3600 cm\u003csup\u003e\u0026ndash;1\u003c/sup\u003e indicates extensive O\u0026ndash;H and N\u0026ndash;H stretching in the PVA\u0026ndash;CS\u0026ndash;mangiferin nanofibers. In the spectra of nanofibers, a strong peak at 1705 cm\u003csup\u003e\u0026ndash;1\u003c/sup\u003e corresponds to C\u0026thinsp;=\u0026thinsp;O stretching[68], while the disappearance of the 1264 cm\u003csup\u003e\u0026ndash;1\u003c/sup\u003e peak (C\u0026ndash;O bond[69] in the carboxyl group of acetic acid) confirms complete solvent removal. The band at 1089 cm\u003csup\u003e\u0026ndash;1\u003c/sup\u003e is attributed to asymmetric C\u0026ndash;O vibrations of the acetate group, and the 844 cm\u003csup\u003e\u0026ndash;1\u003c/sup\u003e band is associated with the C\u0026ndash;H bond vibrations [70, 71].\u003c/p\u003e \u003cp\u003eIn the 600\u0026ndash;1800 cm\u003csup\u003e\u0026ndash;1\u003c/sup\u003e region, the sharp peaks characteristic of mangiferin are replaced by broader bands with fewer peaks, indicating a close association between mangiferin and the polymer matrix.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section3\"\u003e \u003ch2\u003e3.4.2. X\u0026ndash;ray diffraction (XRD) analysis\u003c/h2\u003e \u003cp\u003eThe X-ray diffraction analysis confirmed the incorporation of mangiferin into the PVA\u0026ndash;CS nanofiber matrix. In addition to the characteristic crystalline peaks of PVA and CS, two new peaks at 2θ of 10.6 and 21.2\u0026deg;were observed, with intensity increasing alongside higher mangiferin content, see Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. Analysis of the resulting polymer materials showed that increasing mangiferin loading led to a slight decrease in overall crystallinity and an increase in cell size (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe PVA\u0026ndash;CS\u0026ndash;mangiferin nanofiber lattice parameters\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLattice parameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eAxial Lengths [\u0026Aring;]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eAngles [\u0026deg;]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eCell volume [\u0026Aring;\u003csup\u003e3\u003c/sup\u003e]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCrystallinity (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ea\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eb\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ec\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eα\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eβ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eγ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCS powder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.7371\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.3352\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.0609\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e401.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e48.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePVA powder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.2596\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.2416\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.7092\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e97.188\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e770.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e57.69\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePVA \u0026ndash; CS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.7499\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.2561\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.637\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e92.457\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e798.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e57.45\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePVA \u0026ndash; CS \u0026ndash; 0.5% mangiferin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.2405\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.5343\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.4481\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e92.659\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e848.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e56.59\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePVA \u0026ndash; CS \u0026ndash; 1.0% mangiferin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.4884\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.7364\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.427\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e93.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e869.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e53.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe incorporation of mangiferin into the PVA\u0026ndash;CS nanofibers altered the crystal structure, affecting both the lattice parameters and overall crystallinity. These changes are expected to influence the mechanical, thermal, and drug release properties of the nanofiber matrix.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section3\"\u003e \u003ch2\u003e\u003cem\u003e3.4.3. PVA \u0026ndash; CS \u0026ndash; mangiferin nanofiber thermal analysis\u003c/em\u003e\u003c/h2\u003e \u003cp\u003e \u003cem\u003ea. Differential scanning calorimetry (DSC) analysis\u003c/em\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e presents the DSC heating curves of PVA\u0026ndash;CS\u0026ndash;mangiferin nanofibers at various mangiferin concentrations.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDSC results for the thermal desorption of PVA \u0026ndash; CS \u0026ndash; mangiferin nanofibers.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSample\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eΔH\u003csub\u003ePVA\u003c/sub\u003e (J/g)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eχ\u003csub\u003ePVA\u003c/sub\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eΔH\u003csub\u003eCS\u003c/sub\u003e (J/g)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eT\u003csub\u003eg\u003c/sub\u003e (\u0026deg;C)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eT\u003csub\u003em\u003c/sub\u003e (\u0026deg;C)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCS powder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e268\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePVA powder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e86.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e225\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePVA \u0026ndash; CS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e222; 251\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePVA \u0026ndash; CS \u0026ndash; 0.5% mangiferin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e215; 248\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePVA \u0026ndash; CS \u0026ndash; 1.0% mangiferin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e214; 247\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAccording to the statistical findings in Table\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e, the integration of mangiferin significantly alters the thermal characteristics of nanofibers, resulting in a 10\u0026deg;C decrease in melting temperature and a 5\u0026deg;C increase in glass transition temperature. These shifts in thermal behavior indicate that mangiferin effectively modifies the polymer matrix, supporting its suitability as a therapeutic substance in PVA\u0026ndash;CS nanofiber systems.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section3\"\u003e \u003ch2\u003e3.4.4. Thermogravimetric analysis (TGA)\u003c/h2\u003e \u003cp\u003eTGA curves of heating PVA powder, CS powder, PVA\u0026ndash;CS nanofibers, PVA\u0026ndash;CS\u0026ndash;mangiferin film, and PVA\u0026ndash;CS\u0026ndash;mangiferin nanofibers at different concentrations of mangiferin are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSimilar to PVA powder and PVA\u0026ndash;CS nanofibers, the thermal decomposition of PVA\u0026ndash;CS\u0026ndash;mangiferin composites proceeds in 3 stages, Table\u0026nbsp;\u003cspan refid=\"Tab8\" class=\"InternalRef\"\u003e8\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab8\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 8\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eStages of thermal decomposition and weight reduction of polymer powder and nanofiber samples.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDegradation stages\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePVA powder\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCS powder\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePVA\u0026ndash;CS nanofiber\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePVA \u0026ndash; CS \u0026ndash; 0.5% mangiferin nanofiber\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePVA \u0026ndash; CS \u0026ndash; 1.0% mangiferin nanofiber\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003ePVA \u0026ndash; CS \u0026ndash; 0.5% mangiferin film\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eFirst stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRange (\u003csup\u003eо\u003c/sup\u003eС)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25\u0026ndash;202\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25\u0026ndash;177\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25\u0026ndash;172\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e25\u0026ndash;172\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e25\u0026ndash;172\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e25\u0026ndash;172\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePeaks (\u003csup\u003eo\u003c/sup\u003eC)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e112\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e52; 107\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e52; 112\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e53; 113\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e41; 107\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWeight loss (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e10.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e23.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eSecond stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRange (\u003csup\u003eо\u003c/sup\u003eС)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e202\u0026ndash;367\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e177\u0026ndash;462\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e172\u0026ndash;377\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e172\u0026ndash;377\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e172\u0026ndash;377\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e172\u0026ndash;377\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePeaks (\u003csup\u003eo\u003c/sup\u003eC)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e297\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e302\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e267\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e277; 332\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e282; 337\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e298\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWeight loss (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e77.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e61.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e64.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e57.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e42.76\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eThird stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRange (\u003csup\u003eо\u003c/sup\u003eС)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e367\u0026ndash;527\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e377\u0026ndash;547\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e377\u0026ndash;547\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e377\u0026ndash;547\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e377\u0026ndash;547\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePeaks (\u003csup\u003eo\u003c/sup\u003eC)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e422; 442; 462\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e422; 437; 457\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e442\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e437\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e442\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWeight loss (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e15.72\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe PVA\u0026ndash;CS\u0026ndash;mangiferin film exhibits a higher content of accumulated water and a higher decomposition temperature than the nanofiber samples.\u003c/p\u003e \u003cp\u003eDuring the second stage of thermal decomposition, increasing mangiferin content shifts the primary peaks from 267\u0026deg;С to 277\u0026deg;С and 282\u0026deg;С, with new secondary peaks emerging at 332 and 337\u0026deg;С. For the PVA\u0026ndash;CS\u0026ndash;mangiferin film, the main peak occurs at 298\u0026deg;C, with the secondary peak appearing as a shoulder. In general, the main decomposition peaks of the PVA\u0026ndash;CS nanofiber matrix, with or without mangiferin, are lower than those for individual polymers. This demonstrates that the interactions within the composite are fragile, such as hydrogen bonds or Van der Waals forces.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec23\" class=\"Section3\"\u003e \u003ch2\u003e3.4.5. Tensile property\u003c/h2\u003e \u003cp\u003ePVA\u0026ndash;CS nanofiber matrices with varying amounts of mangiferin were tested for their tensile properties in both vertical and horizontal orientations (Table\u0026nbsp;\u003cspan refid=\"Tab9\" class=\"InternalRef\"\u003e9\u003c/span\u003e, Figs.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e and S6)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab9\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 9\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eParameters of tensile properties of PVA \u0026ndash; CS \u0026ndash; mangiferin nanofibers\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eC\u003csub\u003eMangiferin\u003c/sub\u003e (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTensile strength [MPa]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eElongation at Break [%]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eYoung's modulus [MPa]\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eHorizontal\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eVertical\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eHorizontal\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eHorizontal\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eVertical\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eHorizontal\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.916\u0026thinsp;\u0026plusmn;\u0026thinsp;0.970\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.912\u0026thinsp;\u0026plusmn;\u0026thinsp;0.965\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.07\u0026thinsp;\u0026plusmn;\u0026thinsp;0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.40\u0026thinsp;\u0026plusmn;\u0026thinsp;0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e546.113\u0026thinsp;\u0026plusmn;\u0026thinsp;32.150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e333.086\u0026thinsp;\u0026plusmn;\u0026thinsp;23.851\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e0.5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.005\u0026thinsp;\u0026plusmn;\u0026thinsp;0.754\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.043\u0026thinsp;\u0026plusmn;\u0026thinsp;0.755\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15.20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e470.380\u0026thinsp;\u0026plusmn;\u0026thinsp;18.770\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e342.273\u0026thinsp;\u0026plusmn;\u0026thinsp;18.746\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e1.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.758\u0026thinsp;\u0026plusmn;\u0026thinsp;0.618\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.406\u0026thinsp;\u0026plusmn;\u0026thinsp;0.439\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.48\u0026thinsp;\u0026plusmn;\u0026thinsp;2.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e411.089\u0026thinsp;\u0026plusmn;\u0026thinsp;192.751\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e257.609\u0026thinsp;\u0026plusmn;\u0026thinsp;18.391\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe presence of microheterogeneous structures significantly impacts the physical and mechanical characteristics of PVA\u0026ndash;CS\u0026ndash;mangiferin nanofibers.\u003c/p\u003e \u003cp\u003eAs the mangiferin content increases, the ultimate tensile strength decreases regardless of the deformation axis. For nanofibers oriented in the direction of the deformation axis, tensile strength increases by 50\u0026ndash;60%, elongation at break decreases by 10\u0026ndash;20% on average, and the elastic modulus decreases by 20\u0026ndash;25% (see Table\u0026nbsp;\u003cspan refid=\"Tab9\" class=\"InternalRef\"\u003e9\u003c/span\u003e and Figs.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e and S6).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec24\" class=\"Section3\"\u003e \u003ch2\u003e\u003cem\u003e3.4.4. Drug release from PVA\u0026ndash;CS\u0026ndash;mangiferin nanofiber matrices\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eTo evaluate the release of biologically active substances, 5 mg aliquots of PVA\u0026ndash;CS\u0026ndash;mangiferin nanofibers were immersed in 10 ml of distilled water (pH\u0026thinsp;=\u0026thinsp;6.2) for 12 hours, a duration considered optimal for establishing equilibrium. UV spectral analysis of the resulting solutions, recorded in the 200\u0026ndash;400 nm range, is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e9\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eGiven the solubility of polymers and the low solubility of mangiferin, it remains unclear whether mangiferin is released as a free compound or within the polymer matrix. To address this, aqueous solutions were analyzed after 12 hours of release for the presence of polymers. IR spectroscopy was used to correlate the absorption band intensities of PVA, CS, and mangiferin (see Fig.\u0026nbsp;\u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e10\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab10\" class=\"InternalRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab10\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 10\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDetermination of the presence of polymers in an aqueous solution after 12 hours\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSample\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eInitial spectra\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eProportion\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePVA-CS-mangiferin ratio\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePVA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMangiferin\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFiber with 1% mangiferin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePowder spectra\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3,3757\u0026thinsp;\u0026plusmn;\u0026thinsp;0,0361\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0,0961\u0026thinsp;\u0026plusmn;\u0026thinsp;0,0189\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,0157\u0026thinsp;\u0026plusmn;\u0026thinsp;0,0062\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e~\u0026thinsp;225:62:1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAnalysis showed that both PVA and CS were present in the solution after immersion of nanofibers, with PVA detected in significantly exceeded proportions than CS.\u003c/p\u003e \u003cp\u003eThe release of mangiferin was further evaluated in buffer (pH 7.4, 37\u0026deg;C) using nanofiber matrices obtained from solutions containing 4% PVA, 3% CS, and varying mangiferin concentrations (0.01%, 0.1%, 0.5% and 1.0%). The resulting nanofibers contained 0.14%, 1.41%, 6.67%, and 12.5% mangiferin, respectively. Figure\u0026nbsp;\u003cspan refid=\"Fig11\" class=\"InternalRef\"\u003e11\u003c/span\u003e displays the mangiferin release profiles as determined by high-performance liquid chromatography (HPLC).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe release study in buffer (pH\u0026thinsp;=\u0026thinsp;7.4) showed that nanofibers containing 6.67% mangiferin exhibited greater drug release compared to those with 12.5% mangiferin. Notably, the release profile was characterized by an initial burst release, a phenomenon commonly observed in similar polymer systems.\u003c/p\u003e \u003cp\u003eAdditionally, the effect of prolonged storage was investigated by keeping nanofibers in aqueous solutions for 4 months. As shown in Figures S7, S8, and S9, IR spectroscopy revealed that, over time, stronger intermolecular hydrogen bonds formed between the mangiferin and the PVA\u0026ndash;CS polymer matrix, particularly involving the phenolic hydroxyl at C\u003csub\u003e6\u003c/sub\u003e and C\u003csub\u003e3\u003c/sub\u003e (structure II and structure I, Fig \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAfter 4 months of storage, no change was observed in the position of the absorption bands at 25\u003csup\u003e\u0026deg;\u003c/sup\u003eC and 5\u003csup\u003eo\u003c/sup\u003eC, indicating structural stability of the nanofibers.\u003c/p\u003e \u003cp\u003eIn summary, mangiferin can be incorporated into nanofibers at concentrations 5\u0026ndash;10 times higher than its solubility, without altering its chemical structure. The interaction between mangiferin and the polymer systems is mainly through hydrogen bonding. Variations in mangiferin proportion affect the crystallinity and lattice structure, leading to changes in the thermal and mechanical properties of the nanofibers. Especially, nanofibers containing 6.67% mangiferin exhibited rapid drug release under acidic conditions typical of diseased cells and slow release at neutral pH, corresponding to healthy cells. The integration of mangiferin into PVA\u0026ndash;CS nanofibrous materials using an acetic acid-water-ethanol solvent system enhances both bioavailability and the loading capacity of biologically active substances, up to 12.25%.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"4. Conclusion","content":"\u003cp\u003eThis study presents, for the first time, the fabrication of mangiferin-loaded nanofibers based on PVA and CS and using a ternary acetic acid-water-ethanol solvent system. This approach offers a promising strategy for the development of polymer-based drug delivery systems designed to enhance the bioavailability of compounds with inherently low solubility.\u003c/p\u003e\n\u003cp\u003eKey findings on mangiferin incorporation in PVA–CS nanofiber system:\u003c/p\u003e\n\u003cp\u003e• Mangiferin can be integrated into a nanofiber at concentrations 5–10 times higher than its solubility. The optimal electrospinning solution comprises 4 % PVA, 3 % CS, 0.5 % mangiferin, 45 % CH\u003csub\u003e3\u003c/sub\u003eCOOH, and 15 % C\u003csub\u003e2\u003c/sub\u003eH\u003csub\u003e5\u003c/sub\u003eOH.\u003c/p\u003e\n\u003cp\u003e• The most effective electrospinning parameters were the needle-collector distance of 150mm, the feed rate of 0.2 mL/h, and the applied voltage of 28 kV, resulting in nanofibers with an average diameter of 332 ± 84 nm.\u003c/p\u003e\n\u003cp\u003e• Mangiferin retains its chemical structure and remains stable in both solution and composite nanofibers for at least 40 days at room temperature.\u003c/p\u003e\n\u003cp\u003e• The interaction between mangiferin and the polymer matrix is primarily through hydrogen bonding, which readily dissociates in the aqueous environments.\u003c/p\u003e\n\u003cp\u003e• Increasing mangiferin content leads to a slight decrease in overall crystallinity and an increase in cell size, \u0026nbsp;thereby modulating the glass transition, melting behavior, thermal decomposition and mechanical properties of the polymer nanofiber systems. These results highlight mangiferin’s suitability as a therapeutic agent in PVA-CS nanofiber matrices.\u003c/p\u003e\n\u003cp\u003e• Electrospun nanofibers can accommodate up to 12.25% drug loading and remain stable in water for up to 4 months, as indicated by unchanged infrared spectra peaks.\u003c/p\u003e\n\u003cp\u003e• Nanofibers containing 6.67%, prepared from a solution containing 0.5% mangiferin, exhibited optimal preserved mechanical properties and intact drug release capability, indicating this formulation as the most favorable for therapeutic applications within the PVA–CS–mangiferin nanofiber system.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThe authors have no financial or proprietary interests in any material discussed in this article.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eThi Hong Nhung Vu: investigation, data curation, formal analysis, original draft. Svetlana N. Morozkina: validation, resources, review, and editing. Vera E. Sitnikova: data curation, methodology. Yuliya E. Generalova: data curation, methodology. Nguyen Quang Sang : software. Mayya V. Uspenskaya: methodology, supervision.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eThe authors gratefully acknowledge the Laboratory of the Chemical Centre at ITMO University, Saint Petersburg, Russia, for providing support in carrying out the research and analytical equipment used in this study.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eAll data generated or analyzed during this study are included in this published article and its supplementary information files.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eYou JS, Jones PA (2012) Cancer genetics and epigenetics: two sides of the same coin? 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Procedia Eng 170:31\u0026ndash;35. https://doi.org/10.1016/j.proeng.2017.03.006\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
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