Synthesis and characterisation of a pH-responsive carboxymethylcellulose/metal-organic framework CMC/MIL-88B(Fe) bio-nanocomposite for controlled dexamethasone delivery

Synthesis and characterisation of a pH-responsive carboxymethylcellulose/metal-organic framework CMC/MIL-88B(Fe) bio-nanocomposite for controlled dexamethasone delivery | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Synthesis and characterisation of a pH-responsive carboxymethylcellulose/metal-organic framework CMC/MIL-88B(Fe) bio-nanocomposite for controlled dexamethasone delivery Mohammad Reza Darparesh, Ramin Karimian, Mohammad Reza Khodabakhshi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8038732/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Dec, 2025 Read the published version in Journal of Inorganic and Organometallic Polymers and Materials → Version 1 posted 16 You are reading this latest preprint version Abstract The development of smart drug delivery systems (DDS) has become essential for improving therapeutic efficiency while minimising adverse effects. In this work, a biocompatible carboxymethylcellulose / metal-organic framework composite (CMC/MIL-88B(Fe)) was designed and synthesised through an ultrasound-assisted method to achieve controlled and pH-responsive delivery of dexamethasone (DEX). The obtained material was thoroughly characterised using FT-IR, XRD, TGA/DSC, N₂ adsorption–desorption, and FE-SEM/EDX analyses, confirming the successful formation of MIL-88B(Fe) crystals uniformly distributed within the amorphous CMC network. The composite exhibited a mesoporous structure and good drug-loading performance, achieving an encapsulation efficiency of about 82.7%. In vitro release studies revealed distinct pH-dependent release behaviour, where nearly 78% of DEX was released at acidic pH 5.0 in 240 h compared to 39% at physiological pH 7.4. Drug release kinetics followed the Weibull model (R² >0.96), indicating diffusion-controlled release. To evaluate the biocompatibility and cytotoxic potential, an MTT assay was performed using A549 human lung adenocarcinoma cells. Cells were treated with increasing concentrations (0.05–4 mg/mL) of CMC/MIL-88B(Fe), DEX, and CMC/MIL-88B(Fe)/DEX for 48 h. The CMC/MIL-88B(Fe) maintained over 60% cell viability even at the highest concentration, confirming good biocompatibility and negligible intrinsic cytotoxicity. In contrast, free DEX reduced cell viability to about 45% at 4 mg/mL, while the CMC/MIL-88B(Fe)/DEX system exhibited lower cytotoxicity at the same dose, due to the controlled and sustained drug release from the hybrid matrix. These findings highlight the excellent cytocompatibility and controlled delivery performance of CMC/MIL-88B(Fe), making it a promising platform for safe and efficient corticosteroid delivery in inflammatory and tumour-related applications. Drug delivery system Metal–organic framework Carboxymethylcellulose Bio-nanocomposite Dexamethasone pH-responsive release Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 1. Introduction In recent years, advanced drug delivery systems (DDS) have gained significant attention in biomedical research due to their ability to enhance therapeutic efficacy, prolong drug retention, and minimise systemic toxicity. Nanocarrier-based systems, such as metal–organic frameworks (MOFs), polymeric nanoparticles, dendrimers, and liposomes, have shown great promise due to their tunable porosity, high surface area, and flexible surface chemistry, which enable efficient drug encapsulation and controlled release behaviour [ 1 , 2 ]. Dexamethasone (DEX) is a potent synthetic glucocorticoid widely employed to treat inflammatory and autoimmune diseases such as asthma, rheumatoid arthritis, and acute lung injury. However, its poor aqueous solubility, rapid clearance, and the need for frequent dosing often limit its clinical use. Recent investigations have revealed that DEX can modulate inflammatory responses in human lung epithelial A549 cells by triggering apoptosis through activation of the TGF-β1/Smad2 signalling pathway [ 3 – 5 ]. These findings reinforce the importance of developing advanced nanocarrier systems to achieve targeted and sustained delivery of DEX in pulmonary and inflammatory conditions [ 6 – 8 ]. MOFs have emerged as highly versatile platforms for drug delivery because of their adjustable structure, high porosity, and capacity for functional modification [ 9 , 10 ]. Recent reports highlight the use of frameworks such as ZIF-8, UiO-66, and MIL-101 for the controlled release of therapeutic molecules, including ibuprofen, doxorubicin, 5-fluorouracil, and other therapeutic molecules [ 11 – 13 ]. Among iron-based MOFs, MIL-88(Fe) stands out for its biocompatibility, pH-responsivity, flexibility (breathing framework), and ability to encapsulate various drugs efficiently, such as doxorubicin, 5-fluorouracil, ibuprofen, tetracycline, safranal, luteolin, matrine, and other therapeutic molecules [ 14 – 19 ]. Nonetheless, pristine MOFs often face challenges in aqueous stability, colloidal aggregation, and premature drug leakage under physiological conditions, which significantly limit their direct biomedical applicability. These issues mainly arise from the weak coordination bonds between metal ions and organic linkers in aqueous media, leading to partial framework collapse and uncontrolled release of encapsulated drugs. To overcome these limitations, hybridising MOFs with biopolymers has emerged as a promising strategy to improve their physicochemical and biological performance. Natural polymers such as carboxymethylcellulose (CMC), chitosan, alginate, and hyaluronic acid are frequently incorporated with MOFs to enhance their dispersibility, mechanical integrity, and biocompatibility, while introducing abundant surface functional groups that facilitate hydrogen bonding and electrostatic interactions with drug molecules [ 20 , 21 ]. Among these, CMC has attracted particular attention due to its hydrophilic nature, biodegradability, nontoxicity, and excellent film-forming ability. The carboxyl and hydroxyl groups of CMC can strongly interact with metal nodes and organic linkers of MOFs, effectively preventing particle aggregation and enhancing colloidal stability in aqueous environments. Moreover, CMC provides a flexible matrix that can modulate drug diffusion, reduce burst release, and extend the overall release duration of the encapsulated therapeutic agents [ 22 – 26 ]. The combination of CMC with MOFs, such as MIL-88B(Fe), enhances the structural stability of the framework under physiological conditions while imparting pH-responsive functionalities that can react to the acidic tumour microenvironment, thus making these hybrid systems promising candidates for controlled drug delivery. In this study, a novel pH-responsive bio-nanocomposite based on carboxymethyl cellulose (CMC) and MIL-88B(Fe) was designed and synthesised as a smart carrier for the controlled delivery of dexamethasone (DEX). The incorporation of the biopolymer CMC into the MIL-88B(Fe) framework was intended to enhance the composite’s structural stability, biocompatibility, and aqueous dispersibility, while improving drug-loading efficiency and enabling sustained, environment-sensitive release. Unlike conventional MOF-based systems, this hybrid integrates the hydrophilic and biodegradable characteristics of CMC with the high porosity and crystallinity of MIL-88B(Fe), providing a synergistic platform capable of pH-triggered and diffusion-controlled drug release in acidic tumour-like microenvironments. The synthesised nanocomposite was systematically characterised using FT-IR, XRD, FE-SEM, and N₂ adsorption–desorption analyses to verify its structural, morphological, and surface properties. Moreover, its DEX loading efficiency, encapsulation capacity, and release kinetics were comprehensively evaluated under physiological (pH 7.4) and acidic (pH 5.0) conditions. To further validate its biomedical potential, an in vitro cytotoxicity study was conducted using A549 human lung carcinoma cells to assess the biocompatibility of the carrier and the therapeutic effectiveness of the DEX-loaded system. So, this work aims to establish CMC/MIL-88B(Fe) as a promising and eco-friendly nanoplatform for safe, controlled, and pH-responsive corticosteroid delivery in cancer-related applications. 2. Experimental 2.1. Material In this work 1,4-benzenedicarboxylic acid (BDC), N, N’-dimethylformamide (DMF), ethanol 96%, and hydrochloric acid (HCl) were purchased from Merck Millipore Co. Sodium Carboxymethylcellulose (CMC) with medium viscosity (Viscosity: 400–800 cP, 2%/Lit. in H 2 O (25°C)), anhydrous iron (III) chloride (FeCl 3 ), sodium chloride (NaCl), sodium hydroxide (NaOH), sodium phosphate dibasic (Na 2 HPO 4 ), potassium phosphate monobasic (KH 2 PO 4 ), was purchased from Sigma-Aldrich Co. Dexamethasone (DEX) was achieved from Daropakhsh Pharmaceuticals Co. (Iran). Also, distilled water was used throughout all experiments. 2.2. Characterisation of materials Fourier-transform infrared (FT-IR) spectroscopy was used to characterise the functional groups present in the synthesised carriers using a Bruker ALPHA II spectrophotometer within the 4000–400 cm⁻¹ range and KBr pellets. The crystalline structure of the samples was analysed by X-ray diffraction (XRD) at room temperature using a PANalytical X’Pert PRO diffractometer equipped with a Cu anode source. Thermal analyses (TGA and DSC) were conducted using a NETZSCH STA 601 HT analyser with Proteus software, under an nitrogen atmosphere at a heating rate of 10°C min⁻¹. Nitrogen adsorption–desorption isotherms were recorded on a BELsorp gas adsorption analyser (Japan) to determine surface characteristics. The surface morphology and elemental composition were observed using a KYKY EM8000F field-emission scanning electron microscope (FE-SEM) coupled with an EDX detector. 2.3. Synthesis of CMC/MIL-88B(Fe) composite The CMC/MIL-88B(Fe) composite was prepared by a previously reported synthesis method with a few changes [ 27 , 22 , 28 , 37 ]. In this way, the BDC (3 mmol, 0.487 g) was dissolved in 10 mL of DMF, and at the same time, the anhydrous (3 mmol, 0.498 g) was dissolved in 10 mL of DMF. Then, two solutions of BDC and FeCl3 were added to each other and mixed on a magnetic stirrer for 5 min. A mixture of ethanol and water (1:1, v/v, 20 mL) was added to the reaction system and sonicated for 30 min to prepare the MOF precursor. Subsequently, CMC solution (50 mL, 1% w/v) was introduced and sonicated for another 30 min. The resulting mixture was then heated at 85°C under continuous stirring (300 rpm) for 12 h. After cooling, the precipitate was collected by centrifugation and repeatedly washed with DMF, deionized water, and ethanol. The obtained CMC/MIL-88B(Fe) composite was finally dried under vacuum at 45°C overnight. 2.4. DEX loading The DEX loading process was adapted from previously reported methods with slight modifications [ 29 , 30 ]. Briefly, 50 mg of CMC/MIL-88B(Fe) was dispersed in 50 mL of DEX solution (5 mg/50 mL) and gently shaken in the dark for 48 h at room temperature. The obtained DEX-loaded composite was then washed thoroughly with distilled water to remove unbound drug and vacuum-dried overnight at ambient temperature. The supernatant was analysed by UV–Vis spectrophotometry at 242 nm to quantify the DEX using a standard calibration curve, and the drug encapsulation efficiency (DEE) was calculated according to Eq. (1 ) : $$\:\mathbf{D}\mathbf{E}\mathbf{E}\left(\mathbf{\%}\right)\:=\:\frac{\left(\varvec{A}\varvec{m}\varvec{o}\varvec{u}\varvec{n}\varvec{t}\:\varvec{o}\varvec{f}\:\varvec{d}\varvec{r}\varvec{u}\varvec{g}\varvec{s}\:\varvec{i}\varvec{n}\:\varvec{c}\varvec{a}\varvec{r}\varvec{r}\varvec{i}\varvec{e}\varvec{r}\right(\varvec{m}\varvec{g}\left)\right)}{\left(\varvec{I}\varvec{n}\varvec{i}\varvec{t}\varvec{i}\varvec{a}\varvec{l}\:\varvec{a}\varvec{m}\varvec{o}\varvec{u}\varvec{n}\varvec{t}\:\varvec{o}\varvec{f}\:\varvec{d}\varvec{r}\varvec{u}\varvec{g}\varvec{s}\right(\varvec{m}\varvec{g}\left)\right)\:}$$ (1) 2.5. In vitro DEX release studies The release behaviour of DEX was examined following previously reported methods [ 31 , 32 ]. Briefly, 10 mg of DEX-loaded CMC/MIL-88B(Fe) composite was dispersed in 10 mL of phosphate-buffered saline (PBS, pH 7.4) and sodium acetate buffer (SAB, pH 5.0), and incubated at 37°C under continuous shaking. At predetermined intervals, 2 mL of the medium was withdrawn and replaced with an equal volume of fresh buffer. The released DEX concentration was determined using UV–Vis spectrophotometry at 242 nm, based on a standard calibration curve, and the cumulative release percentage was calculated according to Eq. (2 ) : (2) \(\:\mathbf{R}\mathbf{e}\mathbf{l}\mathbf{e}\mathbf{a}\mathbf{s}\mathbf{e}\mathbf{d}\:\mathbf{d}\mathbf{r}\mathbf{u}\mathbf{g}\left(\mathbf{\%}\right)\:=\:\frac{\left(\varvec{C}\varvec{u}\varvec{m}\varvec{u}\varvec{l}\varvec{a}\varvec{t}\varvec{i}\varvec{v}\varvec{e}\:\varvec{w}\varvec{e}\varvec{i}\varvec{g}\varvec{h}\varvec{t}\:\varvec{o}\varvec{f}\:\varvec{r}\varvec{e}\varvec{l}\varvec{e}\varvec{a}\varvec{s}\varvec{e}\varvec{d}\:\varvec{D}\varvec{E}\varvec{X}\right(\varvec{m}\varvec{g}\left)\right)\:}{\left(\varvec{T}\varvec{o}\varvec{t}\varvec{a}\varvec{l}\:\varvec{w}\varvec{e}\varvec{i}\varvec{g}\varvec{h}\varvec{t}\:\varvec{o}\varvec{f}\:\varvec{l}\varvec{o}\varvec{a}\varvec{d}\varvec{e}\varvec{d}\:\varvec{D}\varvec{E}\varvec{X}\right(\varvec{m}\varvec{g}\left)\right)}\) 2.6. Cytotoxicity study The cytotoxic effects of CMC/MIL-88B(Fe), CMC/MIL-88B(Fe)/DEX, and free DEX were evaluated in A549 human lung epithelial cells using the MTT colorimetric assay. In this assay, viable cells convert MTT into insoluble purple formazan crystals through mitochondrial enzyme activity. A549 cells were maintained in DMEM supplemented with 10% FBS and 1% pen-Strep under standard conditions (37°C, 5% CO₂). Cells were seeded in 96-well plates (1 × 10⁴ cells/well) and, after 24 h of attachment, exposed to increasing concentrations (0.05–4 mg/mL) of each formulation for 48 h. After incubation, the medium was replaced with MTT solution (0.5 mg/mL) and incubated for 2–4 h to allow formazan formation. The crystals were then dissolved in DMSO, and absorbance was measured at 570 nm using a microplate reader (Biotek, USA). Cell viability and cytotoxicity were calculated as described in equations (3) and (4) : (3) \(\:\varvec{C}\varvec{y}\varvec{t}\varvec{o}\varvec{t}\varvec{o}\varvec{x}\varvec{i}\varvec{c}\varvec{i}\varvec{t}\varvec{y}\:\left(\mathbf{\%}\right)=\:\left[1-\:\frac{{\varvec{A}}_{\varvec{t}\varvec{r}\varvec{e}\varvec{a}\varvec{t}\varvec{e}\varvec{d}}}{{\varvec{A}}_{\varvec{c}\varvec{o}\varvec{n}\varvec{t}\varvec{r}\varvec{o}\varvec{l}}}\right]\times\:100\) (4) \(\:\varvec{V}\varvec{i}\varvec{a}\varvec{b}\varvec{i}\varvec{l}\varvec{i}\varvec{t}\varvec{y}\:\left(\varvec{\%}\right)=100-\varvec{C}\varvec{y}\varvec{t}\varvec{o}\varvec{t}\varvec{o}\varvec{x}\varvec{i}\varvec{c}\varvec{i}\varvec{t}\varvec{y}\:\left(\varvec{\%}\right)\) 3. Results and discussion 3.1. Preparation of CMC/MIL-88(Fe) composite In this study, MIL-88B(Fe) was synthesised in situ in CMC solution via an ultrasound-assisted approach. This green and cost-effective technique is frequently employed for MOF fabrication due to its simplicity and mild reaction conditions [ 33 , 34 , 35 , 25 ]. In our synthesis route, the carboxyl groups of CMC coordinated with Fe ions from the MIL-88B(Fe) precursors, promoting composite formation. The mixture was sonicated, heated at 85°C, and maintained for 12 h to yield the CMC/MIL-88B(Fe) ( Scheme 1 ) . The obtained composite serves as an environmentally friendly and biocompatible carrier for DEX, providing a controlled release behaviour. 3.2. FT-IR Analysis The FT-IR spectra of CMC, CMC/MIL-88B(Fe), and DEX-loaded CMC/MIL-88B(Fe) composites (Fig. 1) confirm the successful synthesis of the composite and the efficient loading of DEX. In the CMC spectrum, the broad absorption at 3417 cm⁻¹ corresponds to O–H stretching, and the band at 2922 cm⁻¹ is attributed to C–H vibrations. The peaks at 1596 cm⁻¹ and 1058 cm⁻¹ are associated with the asymmetric stretching of carboxylate (COO⁻) and C–O–C bonds, respectively, confirming the polysaccharide’s functional groups that facilitate coordination with the metal framework. Upon the formation of the CMC/MIL-88B(Fe) composite, significant spectral shifts are observed. The carbonyl band of the terephthalate linker (originally near 1700 cm⁻¹ in pure BDC) shifts to 1605 cm⁻¹, indicating coordination between Fe³⁺ ions and carboxylate groups, thus verifying the successful formation of the MIL-88B(Fe) structure [ 36 , 27 ]. A new absorption at 563 cm⁻¹ corresponds to the Fe–O stretching vibration, further confirming MOF formation. Additionally, the broad O–H band around 3388 cm⁻¹ becomes more intense, suggesting strong hydrogen bonding between CMC chains and the MOF surface, which stabilises the composite framework [ 37 ]. After DEX loading, new and shifted bands emerge, notably at 1724 cm⁻¹, corresponding to the carbonyl (C = O) groups of dexamethasone, and intensified O–H stretching at 3410 cm⁻¹ due to hydrogen-bonding interactions. Minor shifts in the 1610 cm⁻¹ and 1050 cm⁻¹ regions indicate molecular interactions between DEX and both CMC and MIL-88B(Fe) functional groups. These observations confirm that dexamethasone has been successfully incorporated within the composite through physical adsorption and hydrogen bonding. Overall, the FT-IR results substantiate the formation of the CMC/MIL-88B(Fe) hybrid and the effective encapsulation of DEX within its structure. Fig. ‌1. FT-IR spectrum of a) CMC, b) CMC/MIL-88B(Fe), c) CMC/MIL-88B(Fe)/DEX 3.3. XRD analysis The X-ray diffraction pattern of the CMC/MIL-88B(Fe) nanocomposite is shown in Figure ‌2 . As can be seen, distinct peaks appear at angles ‌2θ = 9.4°, ‌11.6°, ‌17.5°, ‌18.6°, ‌21.3°, ‌35.3°, which are consistent with the diffraction pattern reported for MIL-88B(Fe) and are related to the (100), (101), (102), (110) and (220) crystal planes. The presence of these sharp and distinct peaks indicates proper crystal order and successful formation of the MIL-88B(Fe) crystalline phase in the nanocomposite structure. A broad peak is observed in the region around 2θ ≈ 20°-45° of the spectrum, which is a characteristic of amorphous CMC and arises from the irregular structure of its polymer chains. Therefore, the simultaneous presence of sharp peaks related to MIL-88B(Fe) and broad peaks related to CMC indicates that the synthesised composite contains MIL-88B(Fe) crystalline frameworks well distributed in the amorphous CMC polymer matrix [38,39,27] . Fig. ‌2. XRD spectrum of CMC/MIL-88B(Fe) 3.4. Thermal Analysis (TGA/DSC) The thermal properties of the CMC/MIL-88B(Fe) composite were evaluated using simultaneous thermogravimetric (TGA) and differential scanning calorimetric (DSC) analyses over the temperature range of 25–700°C ( Figure ‌3 ). The TGA profile revealed a total weight loss of approximately 63.28%, leaving a stable residue of 36.7%, which is mainly attributed to the formation of thermally stable iron oxide species (Fe₂O₃). The initial slight mass reduction below 150°C (around 5–8%) corresponds to the evaporation of physically adsorbed moisture and the removal of residual solvents such as DMF and ethanol, trapped within the composite’s porous framework. The second weight-loss region observed between 150 and 300°C can be assigned to the partial degradation of carboxymethyl cellulose (CMC) chains, involving dehydration and decarboxylation of labile hydroxyl and carboxyl groups. This stage marks the onset of chemical degradation and indicates the beginning of the breakdown of polymer–metal coordination bonds. The most significant decomposition step occurs between 300 and 430°C, accompanied by a sharp exothermic DSC peak at 373°C (− 5.693 mW/mg). This strong endothermic event reflects the collapse of the MIL-88B(Fe) framework and thermal decomposition of both the BDC organic linker and the polymeric CMC matrix. Beyond 450°C, the TGA curve becomes nearly constant, indicating the formation of a thermally stable inorganic phase. This stability is consistent with the conversion of iron-based nodes into Fe₂O₃, as commonly observed in Fe–MOF systems. These results confirm that the CMC/MIL-88B(Fe) composite remains thermally stable up to around 250°C, after which gradual decomposition of the organic framework dominates. The significant residual mass further supports the hybrid organic–inorganic composition and the inherent thermal robustness conferred by the iron oxide component. Fig. ‌3. TGA and DSC analysis of CMC/MIL-88B(Fe) 3.5. N 2 adsorption–desorption analysis The nitrogen (N 2 ) adsorption–desorption curve of the CMC/MIL-88B(Fe) composite is shown in Fig. 4 ‌. As can be seen, the isotherm clearly has an S-shaped shape with a rapid increase in the adsorption volume in the high partial pressure region ( p/p₀ >0.8). This behaviour is consistent with the type IV isotherm according to the IUPAC classification and indicates the presence of a mesoporous structure in the sample. In addition, the hysteresis loop between the adsorption and desorption curves suggests the presence of open pores with irregular or cylindrical shapes in the composite framework. Therefore, the presence of a hysteresis loop and the sharp increase in adsorption at high pressures are evidence of the mesoporous nature and high specific surface area of ​​the CMC/MIL-88B(Fe) nanocomposite [ 40 , 41 ]. These features make it suitable for DEX drug adsorption and delivery. Fig. ‌4. N 2 adsorption–desorption analysis of CMC/MIL-88B(Fe) composite 3.6. FE-SEM and EDX Analyses In order to investigate the microstructure and elemental composition of the synthesised composite, field emission electron microscopy (FE-SEM) and energy dispersive X-ray spectroscopy (EDX) analyses were performed along with elemental mapping (EDX-Map). FE-SEM images show that the sample surface has a heterogeneous but regular structure, consisting of a large number of MIL-88B(Fe) rod- and spindle-like octahedral particles, distributed relatively uniformly in the CMC polymer matrix ( Figure ‌5A ). This morphology is characteristic of the crystalline phase of MIL-88B(Fe), and its presence in the sample indicates the successful formation of a metal-organic framework within the CMC network [22,27,28] . The predominant particle size is in the submicron to about 1 µm range. The relatively rough and textured surface observed in the FESEM images indicates the effective interaction between the CMC polymer chains and the MIL-88B(Fe) particles. The carboxyl and hydroxyl functional groups present in the CMC formed coordination bonds with the Fe³⁺ ions, causing the uniform nucleation and controlled growth of the MOF structure in the polymer matrix. This phenomenon led to the formation of a stable hybrid structure with high adhesion between the organic and inorganic phases. The results of EDX analysis indicate the presence of carbon, oxygen, and iron in the composition of the sample (Fig. 5 B). The high percentage of carbon and oxygen is consistent with the polysaccharide nature of CMC, while the presence of iron indicates the successful formation of the MIL-88B(Fe) metal framework in the composite structure. In addition, the elemental mapping results obtained from a 100 µm area showed a relatively homogeneous and uniform distribution of Fe, C, and O elements across the sample surface (Fig. 5 C). This uniformity of elemental distribution is a strong confirmation of the proper dispersion of MIL-88B(Fe) particles in the CMC matrix and the effective integration of the two phases at the microscopic scale. (A) 3.7. DEX loading and release behaviour studies One of the key factors in evaluating a suitable platform for drug delivery is its capacity to load therapeutic agents effectively, and to ensure a controlled and sustained release. According to the experimental findings, the DEX loading efficiency of CMC/MIL-88B (Fe) was 82.7%, highlighting its remarkable loading ability and strong potential as an efficient drug delivery carrier. The enhanced DEX loading in the synthesised CMC/MIL-88B(Fe) composite can be attributed to multiple interactions between DEX molecules and the functional groups of the CMC chains, as well as the porous framework of MIL-88B(Fe), including electrostatic attractions and hydrogen bonding. Figure 6 depicts the cumulative release behaviour of DEX under acidic (pH 5) and physiological (pH 7.4) conditions. The release of DEX from the CMC/MIL-88B(Fe) composite exhibited a pronounced pH-dependent behaviour. Approximately 78% of DEX was released at pH 5 in 240 h, whereas only about 39% was released at pH 7.4. This difference can be attributed to the influence of pH on the interactions between DEX and the carrier matrix. Under acidic conditions, pH 5, the carboxyl groups of CMC are partially protonated, reducing the electrostatic interactions between the negatively charged polymer chains and DEX molecules. Additionally, hydrogen bonding between DEX and the CMC/MIL-88B(Fe) framework is partially disrupted in acidic environments. Together, these effects facilitate a higher release of DEX under acidic conditions. In contrast, at physiological pH 7.4, the carboxyl groups remain largely deprotonated, maintaining stronger electrostatic attractions and more stable hydrogen bonding with DEX, resulting in slower and more controlled drug release. Therefore, this pH-responsive release behavior suggests that the CMC/MIL-88B(Fe) composite is a promising carrier for stimuli-responsive drug delivery, exhibiting enhanced release under acidic conditions (such as in tumour tissues or inflammatory) while maintaining controlled release under physiological conditions. Moreover, the in vitro DEX release data were fitted to five different kinetic models to elucidate the release mechanism from CMC/MIL-88B(Fe). Among these models, the Weibull model exhibited the best correlation with the experimental data at both pH 7.4 and pH 5, indicating that the release process was primarily governed by a diffusion-controlled mechanism (Table 1 ). These results suggest that the CMC/MIL-88B(Fe)/DEX nanocomposite possesses great potential for achieving sustained and controlled release of the DEX, particularly under acidic microenvironment conditions [ 42 – 44 ]. Table 1 Kinetic models, equations, and coefficient of determination of DEX release from CMC/MIL-88B(Fe)/DEX at pH 7.4 and pH 5. Kinetic models Equation Coefficient of determination (R 2 ) pH 7.4 pH 5 Zero-order F = k 0 .t 0.738 0.825 First-order ln(1-F) = k f .t 0.585 0.561 Higuchi F = k H .t 1/2 0.458 0.941 Weibull ln[-ln(1-F)] = -ß ln t d + ß ln t 0.962 0.971 Korsmeyer-Peppas M t /M ∞ = K.t n 0.952 0.934 Note : k 0 , k f , and k H represent the drug release constants; t d denotes the timescale of the process, and F indicates the drug release fraction at time t. 3.8. Cytotoxicity study To evaluate the biocompatibility and cytotoxic potential of the synthesised composite, an MTT assay was performed using human lung adenocarcinoma cells (A549) [ 3 – 5 , 45 – 47 ]. Cells were exposed to increasing concentrations (0.05–4 mg/mL) of CMC/MIL-88B(Fe), DEX, and CMC/MIL-88B(Fe)/DEX for 48 h, and the cell viability percentages were determined relative to the untreated control (100%). As shown in Fig. 7 , all concentrations exhibited a dose-dependent decrease in cell viability, indicating concentration-dependent cytotoxicity. The blank CMC/MIL-88B nanocomposite maintained more than 60% cell viability even at the highest tested concentration (4 mg/mL), confirming its good biocompatibility and negligible intrinsic cytotoxicity. This result suggests that the MOF–polymer hybrid matrix of CMC/MIL-88B(Fe) is suitable for biomedical applications. In contrast, free DEX exhibited marked cytotoxicity toward A549 cells, with viability dropping to approximately 45% at 4 mg/mL, demonstrating the potent cellular response induced by the drug. Interestingly, the CMC/MIL-88B/DEX composite showed significantly lower cytotoxicity compared to free DEX at the same concentrations. This reduction in cytotoxicity can be attributed to the controlled and sustained release behaviour of DEX from the CMC/MIL-88B(Fe) matrix, which minimises the initial burst release and limits direct drug–cell interactions. The structural integrity of the MIL-88B(Fe) framework, combined with the hydrophilic CMC coating, likely contributed to a slower drug diffusion rate and reduced acute toxicity. So, the results highlight the excellent cytocompatibility of the carrier and confirm that CMC/MIL-88B can serve as a safe and efficient platform for controlled dexamethasone delivery in A549 cells. 4. Conclusions In this study, a novel pH-responsive and biocompatible CMC/MIL-88B(Fe) bio-nanocomposite was successfully synthesised and demonstrated to be an efficient carrier for the controlled delivery of dexamethasone. Structural and morphological characterisations confirmed the successful integration of MIL-88B(Fe) within the CMC matrix, forming a stable mesoporous framework with enhanced surface area and uniform particle distribution. The nanocomposite exhibited a high drug encapsulation efficiency (82.7%) and distinct pH-dependent release behaviour, releasing approximately 78% of DEX at acidic pH 5.0 and only 39% at physiological pH 7.4. This selective release confirms the system’s potential for targeted drug delivery under tumour-like conditions. The MTT assay on A549 lung carcinoma cells revealed that the CMC/MIL-88B(Fe) carrier was highly biocompatible, maintaining over 60% cell viability even at high concentrations, while DEX-loaded composite exhibited reduced cytotoxicity compared to free DEX due to sustained and controlled drug release. These findings demonstrate that integrating CMC with MIL-88B(Fe) enhances both structural stability and therapeutic performance while minimising burst release and drug-induced toxicity. Overall, the developed CMC/MIL-88B(Fe) composite offers a promising, eco-friendly, and effective platform for the controlled and localised delivery of corticosteroids such as dexamethasone, particularly in inflammatory or tumour microenvironments characterised by acidic conditions. Future studies could focus on in vivo evaluations and surface functionalization strategies to further optimise its targeted delivery potential and pharmacological efficacy. Declarations Conflict of Interest The authors declare that they have no conflict of interest in this study. Availability of Data and Material Data and materials related to this study can be provided by request. Authors' Contributions Mohammad Reza Darparesh: Conceptualization, Methodology, Formal analysis, Validation, Resources, Investigation, Visualization, Writing - Original Draft, Writing - Review & Editing, Project administration. Ramin Karimian: Formal analysis, Writing - Review & Editing. Mohammad Reza Khodabakhshi: Supervision, Conceptualization, Validation, Writing - Original Draft, Writing - Review & Editing, Project administration. Acknowledgement The authors would like to express their sincere gratitude to all colleagues and collaborators who contributed to this research. Their valuable assistance, insightful discussions, and technical support are greatly appreciated. References Chenxi Z, Hemmat A, Thi N, Afrand M. Nanoparticle-enhanced drug delivery systems: An up-to-date review. Journal of Molecular Liquids. 2025:126999. DOI: https://doi.org/10.1016/j.molliq.2025.126999 Ezike TC, Okpala US, Onoja UL, Nwike CP, Ezeako EC, Okpara OJ, et al. 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Dhorai N, Manickam P, Rangaraj S, Venkatachalam R. Synthesis, Characterization of C-Zn/Pd-Np as Potential Nanocomposites Against Human Lung Cancer Cells (A549) and Pathogenic Microorganisms. Journal of Inorganic and Organometallic Polymers and Materials. 2024;34(10):4917-30. DOI: https://doi.org/10.1007/s10904-024-03172-7 Scheme 1 Scheme 1 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Scheme1.jpeg Scheme 1. The representation of CMC/MIL-88B(Fe) preparation. 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15:31:50","extension":"png","order_by":18,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":185082,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-8038732/v1/6b29c2ac5318d3eef4cddcc1.png"},{"id":96196578,"identity":"0432f39c-d7ba-4ea7-967f-03e64f529455","added_by":"auto","created_at":"2025-11-18 15:31:49","extension":"png","order_by":19,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":55322,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage8.png","url":"https://assets-eu.researchsquare.com/files/rs-8038732/v1/07499649add5ae2f9d9b455e.png"},{"id":96196573,"identity":"0ed4d2eb-ed48-4dc3-a47b-2e34f13323c7","added_by":"auto","created_at":"2025-11-18 15:31:49","extension":"png","order_by":20,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":18169,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage9.png","url":"https://assets-eu.researchsquare.com/files/rs-8038732/v1/1e2b77d41bbef1f87546501d.png"},{"id":96196590,"identity":"456a6b49-202c-43e4-9e3f-be7188b5766e","added_by":"auto","created_at":"2025-11-18 15:31:50","extension":"xml","order_by":21,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":128146,"visible":true,"origin":"","legend":"","description":"","filename":"11cd962ef89c4124b6e393dbcf15393d1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8038732/v1/d7ad9fda056853439ee6ddea.xml"},{"id":96196587,"identity":"9e0d3746-41f8-425c-9612-965a47abd216","added_by":"auto","created_at":"2025-11-18 15:31:50","extension":"html","order_by":22,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":138678,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8038732/v1/26bde0bd568c733c2b01ee80.html"},{"id":96196565,"identity":"1468263b-45bd-4c5f-9b3b-313a03ed3ab7","added_by":"auto","created_at":"2025-11-18 15:31:49","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":178618,"visible":true,"origin":"","legend":"\u003cp\u003eFT-IR spectrum of a) CMC, b) CMC/MIL-88B(Fe), c) CMC/MIL-88B(Fe)/DEX\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8038732/v1/efb16827ef488feb6a1763a7.png"},{"id":96196566,"identity":"d1607fab-4799-4800-9962-a7f81cb1feb7","added_by":"auto","created_at":"2025-11-18 15:31:49","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":156116,"visible":true,"origin":"","legend":"\u003cp\u003eXRD spectrum of CMC/MIL-88B(Fe)\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8038732/v1/b272db53d7961f1e955bd821.png"},{"id":96251835,"identity":"f3b4b2f0-c741-474b-b003-0a4598020a9a","added_by":"auto","created_at":"2025-11-19 07:40:07","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":265767,"visible":true,"origin":"","legend":"\u003cp\u003eTGA and DSC analysis of CMC/MIL-88B(Fe)\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8038732/v1/975769d20588069306037ff9.png"},{"id":96364029,"identity":"e1b4f953-a449-400c-9f7f-6651aa803014","added_by":"auto","created_at":"2025-11-20 10:08:47","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":404016,"visible":true,"origin":"","legend":"\u003cp\u003eN\u003csub\u003e2\u003c/sub\u003e adsorption–desorption analysis of CMC/MIL-88B(Fe) composite\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-8038732/v1/3eff1ef6874d3dcc817e455a.png"},{"id":96252694,"identity":"37f11ad2-6393-4e37-8111-64b05e374d4e","added_by":"auto","created_at":"2025-11-19 07:41:21","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1131044,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A)\u003c/strong\u003e FE-SEM images of the CMC/MIL-88B(Fe) composite at 1 and 2 μm magnifications, \u003cstrong\u003e(B)\u003c/strong\u003e EDX spectrum, and \u003cstrong\u003e(C)\u003c/strong\u003eelemental mapping (EDX-Map) of a 100 µm surface area\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-8038732/v1/f916fbe07890dfa65b3123c5.png"},{"id":96250031,"identity":"69b69d86-33bf-4adf-944e-a375d8840891","added_by":"auto","created_at":"2025-11-19 07:37:11","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":419140,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eIn vitro\u003c/em\u003e release profiles of DEX from CMC/MIL-88B(Fe)/DEX composite at pH 7.4 and pH 5\u003c/p\u003e","description":"","filename":"floatimage8.png","url":"https://assets-eu.researchsquare.com/files/rs-8038732/v1/9c5f383e1ee444af564aabc5.png"},{"id":96196567,"identity":"5e5dcadd-772c-4854-956a-caf45d1ba065","added_by":"auto","created_at":"2025-11-18 15:31:49","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":163544,"visible":true,"origin":"","legend":"\u003cp\u003eViability of A549 cells (%) after 48 h of exposure to varying concentrations of CMC/MIL-88B(Fe), DEX, and CMC/MIL-88B(Fe)/DEX.\u003c/p\u003e","description":"","filename":"floatimage9.png","url":"https://assets-eu.researchsquare.com/files/rs-8038732/v1/edef9a25a63638897cc76bf4.png"},{"id":98814123,"identity":"59733e00-eff7-41ce-b1b2-2a59d9d9422e","added_by":"auto","created_at":"2025-12-22 16:11:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3529411,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8038732/v1/8249ef2e-2189-4bc5-8da7-b7e8ad1a7cae.pdf"},{"id":96196564,"identity":"c11e42d4-2082-40a5-a446-f33282392d75","added_by":"auto","created_at":"2025-11-18 15:31:49","extension":"jpeg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":305650,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScheme 1.\u003c/strong\u003e The representation of CMC/MIL-88B(Fe) preparation.\u003c/p\u003e","description":"","filename":"Scheme1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8038732/v1/4df5ab72edf21c14f532e474.jpeg"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eSynthesis and characterisation of a pH-responsive carboxymethylcellulose/metal-organic framework CMC/MIL-88B(Fe) bio-nanocomposite for controlled dexamethasone delivery\u003c/p\u003e","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eIn recent years, advanced drug delivery systems (DDS) have gained significant attention in biomedical research due to their ability to enhance therapeutic efficacy, prolong drug retention, and minimise systemic toxicity. Nanocarrier-based systems, such as metal\u0026ndash;organic frameworks (MOFs), polymeric nanoparticles, dendrimers, and liposomes, have shown great promise due to their tunable porosity, high surface area, and flexible surface chemistry, which enable efficient drug encapsulation and controlled release behaviour [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDexamethasone (DEX) is a potent synthetic glucocorticoid widely employed to treat inflammatory and autoimmune diseases such as asthma, rheumatoid arthritis, and acute lung injury. However, its poor aqueous solubility, rapid clearance, and the need for frequent dosing often limit its clinical use. Recent investigations have revealed that DEX can modulate inflammatory responses in human lung epithelial A549 cells by triggering apoptosis through activation of the TGF-β1/Smad2 signalling pathway [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. These findings reinforce the importance of developing advanced nanocarrier systems to achieve targeted and sustained delivery of DEX in pulmonary and inflammatory conditions [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMOFs have emerged as highly versatile platforms for drug delivery because of their adjustable structure, high porosity, and capacity for functional modification [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Recent reports highlight the use of frameworks such as ZIF-8, UiO-66, and MIL-101 for the controlled release of therapeutic molecules, including ibuprofen, doxorubicin, 5-fluorouracil, and other therapeutic molecules [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Among iron-based MOFs, MIL-88(Fe) stands out for its biocompatibility, pH-responsivity, flexibility (breathing framework), and ability to encapsulate various drugs efficiently, such as doxorubicin, 5-fluorouracil, ibuprofen, tetracycline, safranal, luteolin, matrine, and other therapeutic molecules [\u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eNonetheless, pristine MOFs often face challenges in aqueous stability, colloidal aggregation, and premature drug leakage under physiological conditions, which significantly limit their direct biomedical applicability. These issues mainly arise from the weak coordination bonds between metal ions and organic linkers in aqueous media, leading to partial framework collapse and uncontrolled release of encapsulated drugs. To overcome these limitations, hybridising MOFs with biopolymers has emerged as a promising strategy to improve their physicochemical and biological performance. Natural polymers such as carboxymethylcellulose (CMC), chitosan, alginate, and hyaluronic acid are frequently incorporated with MOFs to enhance their dispersibility, mechanical integrity, and biocompatibility, while introducing abundant surface functional groups that facilitate hydrogen bonding and electrostatic interactions with drug molecules [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Among these, CMC has attracted particular attention due to its hydrophilic nature, biodegradability, nontoxicity, and excellent film-forming ability. The carboxyl and hydroxyl groups of CMC can strongly interact with metal nodes and organic linkers of MOFs, effectively preventing particle aggregation and enhancing colloidal stability in aqueous environments. Moreover, CMC provides a flexible matrix that can modulate drug diffusion, reduce burst release, and extend the overall release duration of the encapsulated therapeutic agents [\u003cspan additionalcitationids=\"CR23 CR24 CR25\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The combination of CMC with MOFs, such as MIL-88B(Fe), enhances the structural stability of the framework under physiological conditions while imparting pH-responsive functionalities that can react to the acidic tumour microenvironment, thus making these hybrid systems promising candidates for controlled drug delivery.\u003c/p\u003e\u003cp\u003eIn this study, a novel pH-responsive bio-nanocomposite based on carboxymethyl cellulose (CMC) and MIL-88B(Fe) was designed and synthesised as a smart carrier for the controlled delivery of dexamethasone (DEX). The incorporation of the biopolymer CMC into the MIL-88B(Fe) framework was intended to enhance the composite\u0026rsquo;s structural stability, biocompatibility, and aqueous dispersibility, while improving drug-loading efficiency and enabling sustained, environment-sensitive release. Unlike conventional MOF-based systems, this hybrid integrates the hydrophilic and biodegradable characteristics of CMC with the high porosity and crystallinity of MIL-88B(Fe), providing a synergistic platform capable of pH-triggered and diffusion-controlled drug release in acidic tumour-like microenvironments. The synthesised nanocomposite was systematically characterised using FT-IR, XRD, FE-SEM, and N₂ adsorption\u0026ndash;desorption analyses to verify its structural, morphological, and surface properties. Moreover, its DEX loading efficiency, encapsulation capacity, and release kinetics were comprehensively evaluated under physiological (pH 7.4) and acidic (pH 5.0) conditions. To further validate its biomedical potential, an in vitro cytotoxicity study was conducted using A549 human lung carcinoma cells to assess the biocompatibility of the carrier and the therapeutic effectiveness of the DEX-loaded system. So, this work aims to establish CMC/MIL-88B(Fe) as a promising and eco-friendly nanoplatform for safe, controlled, and pH-responsive corticosteroid delivery in cancer-related applications.\u003c/p\u003e"},{"header":"2. Experimental","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1. Material\u003c/h2\u003e\u003cp\u003eIn this work 1,4-benzenedicarboxylic acid (BDC), N, N\u0026rsquo;-dimethylformamide (DMF), ethanol 96%, and hydrochloric acid (HCl) were purchased from Merck Millipore Co. Sodium Carboxymethylcellulose (CMC) with medium viscosity (Viscosity: 400\u0026ndash;800 cP, 2%/Lit. in H\u003csub\u003e2\u003c/sub\u003eO (25\u0026deg;C)), anhydrous iron (III) chloride (FeCl\u003csub\u003e3\u003c/sub\u003e), sodium chloride (NaCl), sodium hydroxide (NaOH), sodium phosphate dibasic (Na\u003csub\u003e2\u003c/sub\u003eHPO\u003csub\u003e4\u003c/sub\u003e), potassium phosphate monobasic (KH\u003csub\u003e2\u003c/sub\u003ePO\u003csub\u003e4\u003c/sub\u003e), was purchased from Sigma-Aldrich Co. Dexamethasone (DEX) was achieved from Daropakhsh Pharmaceuticals Co. (Iran). Also, distilled water was used throughout all experiments.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2. Characterisation of materials\u003c/h2\u003e\u003cp\u003eFourier-transform infrared (FT-IR) spectroscopy was used to characterise the functional groups present in the synthesised carriers using a Bruker ALPHA II spectrophotometer within the 4000\u0026ndash;400 cm⁻\u0026sup1; range and KBr pellets. The crystalline structure of the samples was analysed by X-ray diffraction (XRD) at room temperature using a PANalytical X\u0026rsquo;Pert PRO diffractometer equipped with a Cu anode source. Thermal analyses (TGA and DSC) were conducted using a NETZSCH STA 601 HT analyser with Proteus software, under an nitrogen atmosphere at a heating rate of 10\u0026deg;C min⁻\u0026sup1;. Nitrogen adsorption\u0026ndash;desorption isotherms were recorded on a BELsorp gas adsorption analyser (Japan) to determine surface characteristics. The surface morphology and elemental composition were observed using a KYKY EM8000F field-emission scanning electron microscope (FE-SEM) coupled with an EDX detector.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3. Synthesis of CMC/MIL-88B(Fe) composite\u003c/h2\u003e\u003cp\u003eThe CMC/MIL-88B(Fe) composite was prepared by a previously reported synthesis method with a few changes [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. In this way, the BDC (3 mmol, 0.487 g) was dissolved in 10 mL of DMF, and at the same time, the anhydrous (3 mmol, 0.498 g) was dissolved in 10 mL of DMF. Then, two solutions of BDC and FeCl3 were added to each other and mixed on a magnetic stirrer for 5 min. A mixture of ethanol and water (1:1, v/v, 20 mL) was added to the reaction system and sonicated for 30 min to prepare the MOF precursor. Subsequently, CMC solution (50 mL, 1% w/v) was introduced and sonicated for another 30 min. The resulting mixture was then heated at 85\u0026deg;C under continuous stirring (300 rpm) for 12 h. After cooling, the precipitate was collected by centrifugation and repeatedly washed with DMF, deionized water, and ethanol. The obtained CMC/MIL-88B(Fe) composite was finally dried under vacuum at 45\u0026deg;C overnight.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4. DEX loading\u003c/h2\u003e\u003cp\u003eThe DEX loading process was adapted from previously reported methods with slight modifications [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Briefly, 50 mg of CMC/MIL-88B(Fe) was dispersed in 50 mL of DEX solution (5 mg/50 mL) and gently shaken in the dark for 48 h at room temperature. The obtained DEX-loaded composite was then washed thoroughly with distilled water to remove unbound drug and vacuum-dried overnight at ambient temperature. The supernatant was analysed by UV\u0026ndash;Vis spectrophotometry at 242 nm to quantify the DEX using a standard calibration curve, and the drug encapsulation efficiency (DEE) was calculated according to Eq.\u0026nbsp;(1\u003cb\u003e)\u003c/b\u003e:\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$\\:\\mathbf{D}\\mathbf{E}\\mathbf{E}\\left(\\mathbf{\\%}\\right)\\:=\\:\\frac{\\left(\\varvec{A}\\varvec{m}\\varvec{o}\\varvec{u}\\varvec{n}\\varvec{t}\\:\\varvec{o}\\varvec{f}\\:\\varvec{d}\\varvec{r}\\varvec{u}\\varvec{g}\\varvec{s}\\:\\varvec{i}\\varvec{n}\\:\\varvec{c}\\varvec{a}\\varvec{r}\\varvec{r}\\varvec{i}\\varvec{e}\\varvec{r}\\right(\\varvec{m}\\varvec{g}\\left)\\right)}{\\left(\\varvec{I}\\varvec{n}\\varvec{i}\\varvec{t}\\varvec{i}\\varvec{a}\\varvec{l}\\:\\varvec{a}\\varvec{m}\\varvec{o}\\varvec{u}\\varvec{n}\\varvec{t}\\:\\varvec{o}\\varvec{f}\\:\\varvec{d}\\varvec{r}\\varvec{u}\\varvec{g}\\varvec{s}\\right(\\varvec{m}\\varvec{g}\\left)\\right)\\:}$$\u003c/div\u003e\u003c/div\u003e(1) \u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e2.5. \u003cem\u003eIn vitro\u003c/em\u003e DEX release studies\u003c/h2\u003e\u003cp\u003eThe release behaviour of DEX was examined following previously reported methods [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Briefly, 10 mg of DEX-loaded CMC/MIL-88B(Fe) composite was dispersed in 10 mL of phosphate-buffered saline (PBS, pH 7.4) and sodium acetate buffer (SAB, pH 5.0), and incubated at 37\u0026deg;C under continuous shaking. At predetermined intervals, 2 mL of the medium was withdrawn and replaced with an equal volume of fresh buffer. The released DEX concentration was determined using UV\u0026ndash;Vis spectrophotometry at 242 nm, based on a standard calibration curve, and the cumulative release percentage was calculated according to Eq.\u0026nbsp;(2\u003cb\u003e)\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cb\u003e(2)\u003c/b\u003e \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\mathbf{R}\\mathbf{e}\\mathbf{l}\\mathbf{e}\\mathbf{a}\\mathbf{s}\\mathbf{e}\\mathbf{d}\\:\\mathbf{d}\\mathbf{r}\\mathbf{u}\\mathbf{g}\\left(\\mathbf{\\%}\\right)\\:=\\:\\frac{\\left(\\varvec{C}\\varvec{u}\\varvec{m}\\varvec{u}\\varvec{l}\\varvec{a}\\varvec{t}\\varvec{i}\\varvec{v}\\varvec{e}\\:\\varvec{w}\\varvec{e}\\varvec{i}\\varvec{g}\\varvec{h}\\varvec{t}\\:\\varvec{o}\\varvec{f}\\:\\varvec{r}\\varvec{e}\\varvec{l}\\varvec{e}\\varvec{a}\\varvec{s}\\varvec{e}\\varvec{d}\\:\\varvec{D}\\varvec{E}\\varvec{X}\\right(\\varvec{m}\\varvec{g}\\left)\\right)\\:}{\\left(\\varvec{T}\\varvec{o}\\varvec{t}\\varvec{a}\\varvec{l}\\:\\varvec{w}\\varvec{e}\\varvec{i}\\varvec{g}\\varvec{h}\\varvec{t}\\:\\varvec{o}\\varvec{f}\\:\\varvec{l}\\varvec{o}\\varvec{a}\\varvec{d}\\varvec{e}\\varvec{d}\\:\\varvec{D}\\varvec{E}\\varvec{X}\\right(\\varvec{m}\\varvec{g}\\left)\\right)}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e2.6. Cytotoxicity study\u003c/h2\u003e\u003cp\u003eThe cytotoxic effects of CMC/MIL-88B(Fe), CMC/MIL-88B(Fe)/DEX, and free DEX were evaluated in A549 human lung epithelial cells using the MTT colorimetric assay. In this assay, viable cells convert MTT into insoluble purple formazan crystals through mitochondrial enzyme activity. A549 cells were maintained in DMEM supplemented with 10% FBS and 1% pen-Strep under standard conditions (37\u0026deg;C, 5% CO₂). Cells were seeded in 96-well plates (1 \u0026times; 10⁴ cells/well) and, after 24 h of attachment, exposed to increasing concentrations (0.05\u0026ndash;4 mg/mL) of each formulation for 48 h. After incubation, the medium was replaced with MTT solution (0.5 mg/mL) and incubated for 2\u0026ndash;4 h to allow formazan formation. The crystals were then dissolved in DMSO, and absorbance was measured at 570 nm using a microplate reader (Biotek, USA). Cell viability and cytotoxicity were calculated as described in equations \u003cb\u003e(3)\u003c/b\u003e and \u003cb\u003e(4)\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cb\u003e(3)\u003c/b\u003e \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\varvec{C}\\varvec{y}\\varvec{t}\\varvec{o}\\varvec{t}\\varvec{o}\\varvec{x}\\varvec{i}\\varvec{c}\\varvec{i}\\varvec{t}\\varvec{y}\\:\\left(\\mathbf{\\%}\\right)=\\:\\left[1-\\:\\frac{{\\varvec{A}}_{\\varvec{t}\\varvec{r}\\varvec{e}\\varvec{a}\\varvec{t}\\varvec{e}\\varvec{d}}}{{\\varvec{A}}_{\\varvec{c}\\varvec{o}\\varvec{n}\\varvec{t}\\varvec{r}\\varvec{o}\\varvec{l}}}\\right]\\times\\:100\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(4)\u003c/b\u003e \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\varvec{V}\\varvec{i}\\varvec{a}\\varvec{b}\\varvec{i}\\varvec{l}\\varvec{i}\\varvec{t}\\varvec{y}\\:\\left(\\varvec{\\%}\\right)=100-\\varvec{C}\\varvec{y}\\varvec{t}\\varvec{o}\\varvec{t}\\varvec{o}\\varvec{x}\\varvec{i}\\varvec{c}\\varvec{i}\\varvec{t}\\varvec{y}\\:\\left(\\varvec{\\%}\\right)\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Results and discussion","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e3.1. Preparation of CMC/MIL-88(Fe) composite\u003c/h2\u003e\u003cp\u003eIn this study, MIL-88B(Fe) was synthesised in situ in CMC solution via an ultrasound-assisted approach. This green and cost-effective technique is frequently employed for MOF fabrication due to its simplicity and mild reaction conditions [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In our synthesis route, the carboxyl groups of CMC coordinated with Fe ions from the MIL-88B(Fe) precursors, promoting composite formation. The mixture was sonicated, heated at 85\u0026deg;C, and maintained for 12 h to yield the CMC/MIL-88B(Fe) \u003cb\u003e(\u003c/b\u003eScheme \u003cspan refid=\"Sch1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. The obtained composite serves as an environmentally friendly and biocompatible carrier for DEX, providing a controlled release behaviour.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e3.2. FT-IR Analysis\u003c/h2\u003e\u003cp\u003eThe FT-IR spectra of CMC, CMC/MIL-88B(Fe), and DEX-loaded CMC/MIL-88B(Fe) composites (Fig.\u0026nbsp;1) confirm the successful synthesis of the composite and the efficient loading of DEX. In the CMC spectrum, the broad absorption at 3417 cm⁻\u0026sup1; corresponds to O\u0026ndash;H stretching, and the band at 2922 cm⁻\u0026sup1; is attributed to C\u0026ndash;H vibrations. The peaks at 1596 cm⁻\u0026sup1; and 1058 cm⁻\u0026sup1; are associated with the asymmetric stretching of carboxylate (COO⁻) and C\u0026ndash;O\u0026ndash;C bonds, respectively, confirming the polysaccharide\u0026rsquo;s functional groups that facilitate coordination with the metal framework. Upon the formation of the CMC/MIL-88B(Fe) composite, significant spectral shifts are observed. The carbonyl band of the terephthalate linker (originally near 1700 cm⁻\u0026sup1; in pure BDC) shifts to 1605 cm⁻\u0026sup1;, indicating coordination between Fe\u0026sup3;⁺ ions and carboxylate groups, thus verifying the successful formation of the MIL-88B(Fe) structure [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. A new absorption at 563 cm⁻\u0026sup1; corresponds to the Fe\u0026ndash;O stretching vibration, further confirming MOF formation. Additionally, the broad O\u0026ndash;H band around 3388 cm⁻\u0026sup1; becomes more intense, suggesting strong hydrogen bonding between CMC chains and the MOF surface, which stabilises the composite framework [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. After DEX loading, new and shifted bands emerge, notably at 1724 cm⁻\u0026sup1;, corresponding to the carbonyl (C\u0026thinsp;=\u0026thinsp;O) groups of dexamethasone, and intensified O\u0026ndash;H stretching at 3410 cm⁻\u0026sup1; due to hydrogen-bonding interactions. Minor shifts in the 1610 cm⁻\u0026sup1; and 1050 cm⁻\u0026sup1; regions indicate molecular interactions between DEX and both CMC and MIL-88B(Fe) functional groups. These observations confirm that dexamethasone has been successfully incorporated within the composite through physical adsorption and hydrogen bonding. Overall, the FT-IR results substantiate the formation of the CMC/MIL-88B(Fe) hybrid and the effective encapsulation of DEX within its structure.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eFig. \u0026zwnj;1.\u003c/b\u003e FT-IR spectrum of a) CMC, b) CMC/MIL-88B(Fe), c) CMC/MIL-88B(Fe)/DEX\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e3.3. XRD analysis\u003c/h2\u003e\u003cp\u003eThe X-ray diffraction pattern of the CMC/MIL-88B(Fe) nanocomposite is shown in \u003cb\u003eFigure \u0026zwnj;2\u003c/b\u003e. As can be seen, distinct peaks appear at angles \u0026zwnj;2θ\u0026thinsp;=\u0026thinsp;9.4\u0026deg;, \u0026zwnj;11.6\u0026deg;, \u0026zwnj;17.5\u0026deg;, \u0026zwnj;18.6\u0026deg;, \u0026zwnj;21.3\u0026deg;, \u0026zwnj;35.3\u0026deg;, which are consistent with the diffraction pattern reported for MIL-88B(Fe) and are related to the (100), (101), (102), (110) and (220) crystal planes. The presence of these sharp and distinct peaks indicates proper crystal order and successful formation of the MIL-88B(Fe) crystalline phase in the nanocomposite structure. A broad peak is observed in the region around 2θ\u0026thinsp;\u0026asymp;\u0026thinsp;20\u0026deg;-45\u0026deg; of the spectrum, which is a characteristic of amorphous CMC and arises from the irregular structure of its polymer chains. Therefore, the simultaneous presence of sharp peaks related to MIL-88B(Fe) and broad peaks related to CMC indicates that the synthesised composite contains MIL-88B(Fe) crystalline frameworks well distributed in the amorphous CMC polymer matrix \u003cb\u003e[38,39,27]\u003c/b\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eFig. \u0026zwnj;2.\u003c/b\u003e XRD spectrum of CMC/MIL-88B(Fe)\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003e3.4. Thermal Analysis (TGA/DSC)\u003c/h2\u003e\u003cp\u003eThe thermal properties of the CMC/MIL-88B(Fe) composite were evaluated using simultaneous thermogravimetric (TGA) and differential scanning calorimetric (DSC) analyses over the temperature range of 25\u0026ndash;700\u0026deg;C (\u003cb\u003eFigure \u0026zwnj;3\u003c/b\u003e). The TGA profile revealed a total weight loss of approximately 63.28%, leaving a stable residue of 36.7%, which is mainly attributed to the formation of thermally stable iron oxide species (Fe₂O₃). The initial slight mass reduction below 150\u0026deg;C (around 5\u0026ndash;8%) corresponds to the evaporation of physically adsorbed moisture and the removal of residual solvents such as DMF and ethanol, trapped within the composite\u0026rsquo;s porous framework. The second weight-loss region observed between 150 and 300\u0026deg;C can be assigned to the partial degradation of carboxymethyl cellulose (CMC) chains, involving dehydration and decarboxylation of labile hydroxyl and carboxyl groups. This stage marks the onset of chemical degradation and indicates the beginning of the breakdown of polymer\u0026ndash;metal coordination bonds. The most significant decomposition step occurs between 300 and 430\u0026deg;C, accompanied by a sharp exothermic DSC peak at 373\u0026deg;C (\u0026minus;\u0026thinsp;5.693 mW/mg). This strong endothermic event reflects the collapse of the MIL-88B(Fe) framework and thermal decomposition of both the BDC organic linker and the polymeric CMC matrix. Beyond 450\u0026deg;C, the TGA curve becomes nearly constant, indicating the formation of a thermally stable inorganic phase. This stability is consistent with the conversion of iron-based nodes into Fe₂O₃, as commonly observed in Fe\u0026ndash;MOF systems. These results confirm that the CMC/MIL-88B(Fe) composite remains thermally stable up to around 250\u0026deg;C, after which gradual decomposition of the organic framework dominates. The significant residual mass further supports the hybrid organic\u0026ndash;inorganic composition and the inherent thermal robustness conferred by the iron oxide component.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eFig. \u0026zwnj;3.\u003c/b\u003e TGA and DSC analysis of CMC/MIL-88B(Fe)\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003e3.5. N\u003csub\u003e2\u003c/sub\u003e adsorption\u0026ndash;desorption analysis\u003c/h2\u003e\u003cp\u003eThe nitrogen (N\u003csub\u003e2\u003c/sub\u003e) adsorption\u0026ndash;desorption curve of the CMC/MIL-88B(Fe) composite is shown in \u003cb\u003eFig.\u0026nbsp;4\u003c/b\u003e\u0026zwnj;. As can be seen, the isotherm clearly has an S-shaped shape with a rapid increase in the adsorption volume in the high partial pressure region (\u003cem\u003ep/p₀\u003c/em\u003e \u0026gt;0.8). This behaviour is consistent with the type IV isotherm according to the IUPAC classification and indicates the presence of a mesoporous structure in the sample. In addition, the hysteresis loop between the adsorption and desorption curves suggests the presence of open pores with irregular or cylindrical shapes in the composite framework. Therefore, the presence of a hysteresis loop and the sharp increase in adsorption at high pressures are evidence of the mesoporous nature and high specific surface area of ​​the CMC/MIL-88B(Fe) nanocomposite [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. These features make it suitable for DEX drug adsorption and delivery.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eFig. \u0026zwnj;4.\u003c/b\u003e N\u003csub\u003e2\u003c/sub\u003e adsorption\u0026ndash;desorption analysis of CMC/MIL-88B(Fe) composite\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003e3.6. FE-SEM and EDX Analyses\u003c/h2\u003e\u003cp\u003eIn order to investigate the microstructure and elemental composition of the synthesised composite, field emission electron microscopy (FE-SEM) and energy dispersive X-ray spectroscopy (EDX) analyses were performed along with elemental mapping (EDX-Map). FE-SEM images show that the sample surface has a heterogeneous but regular structure, consisting of a large number of MIL-88B(Fe) rod- and spindle-like octahedral particles, distributed relatively uniformly in the CMC polymer matrix (\u003cb\u003eFigure \u0026zwnj;5A\u003c/b\u003e). This morphology is characteristic of the crystalline phase of MIL-88B(Fe), and its presence in the sample indicates the successful formation of a metal-organic framework within the CMC network \u003cb\u003e[22,27,28]\u003c/b\u003e. The predominant particle size is in the submicron to about 1 \u0026micro;m range. The relatively rough and textured surface observed in the FESEM images indicates the effective interaction between the CMC polymer chains and the MIL-88B(Fe) particles. The carboxyl and hydroxyl functional groups present in the CMC formed coordination bonds with the Fe\u0026sup3;⁺ ions, causing the uniform nucleation and controlled growth of the MOF structure in the polymer matrix. This phenomenon led to the formation of a stable hybrid structure with high adhesion between the organic and inorganic phases. The results of EDX analysis indicate the presence of carbon, oxygen, and iron in the composition of the sample (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e5\u003c/span\u003eB). The high percentage of carbon and oxygen is consistent with the polysaccharide nature of CMC, while the presence of iron indicates the successful formation of the MIL-88B(Fe) metal framework in the composite structure. In addition, the elemental mapping results obtained from a 100 \u0026micro;m area showed a relatively homogeneous and uniform distribution of Fe, C, and O elements across the sample surface (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e5\u003c/span\u003eC). This uniformity of elemental distribution is a strong confirmation of the proper dispersion of MIL-88B(Fe) particles in the CMC matrix and the effective integration of the two phases at the microscopic scale.\u003c/p\u003e\u003cp\u003e(A)\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003e3.7. DEX loading and release behaviour studies\u003c/h2\u003e\u003cp\u003eOne of the key factors in evaluating a suitable platform for drug delivery is its capacity to load therapeutic agents effectively, and to ensure a controlled and sustained release. According to the experimental findings, the DEX loading efficiency of CMC/MIL-88B (Fe) was 82.7%, highlighting its remarkable loading ability and strong potential as an efficient drug delivery carrier. The enhanced DEX loading in the synthesised CMC/MIL-88B(Fe) composite can be attributed to multiple interactions between DEX molecules and the functional groups of the CMC chains, as well as the porous framework of MIL-88B(Fe), including electrostatic attractions and hydrogen bonding. Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e6\u003c/span\u003e depicts the cumulative release behaviour of DEX under acidic (pH 5) and physiological (pH 7.4) conditions. The release of DEX from the CMC/MIL-88B(Fe) composite exhibited a pronounced pH-dependent behaviour. Approximately 78% of DEX was released at pH 5 in 240 h, whereas only about 39% was released at pH 7.4. This difference can be attributed to the influence of pH on the interactions between DEX and the carrier matrix. Under acidic conditions, pH 5, the carboxyl groups of CMC are partially protonated, reducing the electrostatic interactions between the negatively charged polymer chains and DEX molecules. Additionally, hydrogen bonding between DEX and the CMC/MIL-88B(Fe) framework is partially disrupted in acidic environments. Together, these effects facilitate a higher release of DEX under acidic conditions. In contrast, at physiological pH 7.4, the carboxyl groups remain largely deprotonated, maintaining stronger electrostatic attractions and more stable hydrogen bonding with DEX, resulting in slower and more controlled drug release. Therefore, this pH-responsive release behavior suggests that the CMC/MIL-88B(Fe) composite is a promising carrier for stimuli-responsive drug delivery, exhibiting enhanced release under acidic conditions (such as in tumour tissues or inflammatory) while maintaining controlled release under physiological conditions.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eMoreover, the \u003cem\u003ein vitro\u003c/em\u003e DEX release data were fitted to five different kinetic models to elucidate the release mechanism from CMC/MIL-88B(Fe). Among these models, the Weibull model exhibited the best correlation with the experimental data at both pH 7.4 and pH 5, indicating that the release process was primarily governed by a diffusion-controlled mechanism (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). These results suggest that the CMC/MIL-88B(Fe)/DEX nanocomposite possesses great potential for achieving sustained and controlled release of the DEX, particularly under acidic microenvironment conditions [\u003cspan additionalcitationids=\"CR43\" citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e].\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\u003eKinetic models, equations, and coefficient of determination of DEX release from CMC/MIL-88B(Fe)/DEX at pH 7.4 and pH 5.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eKinetic models\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eEquation\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003eCoefficient of determination (R\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003epH 7.4\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003epH 5\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\u003eZero-order\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eF\u0026thinsp;=\u0026thinsp;k\u003csub\u003e0\u003c/sub\u003e.t\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.738\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.825\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFirst-order\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eln(1-F)\u0026thinsp;=\u0026thinsp;k\u003csub\u003ef\u003c/sub\u003e.t\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.585\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.561\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHiguchi\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eF\u0026thinsp;=\u0026thinsp;k\u003csub\u003eH\u003c/sub\u003e.t\u003csup\u003e1/2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.458\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.941\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eWeibull\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eln[-ln(1-F)] = -\u0026szlig; ln t\u003csub\u003ed\u003c/sub\u003e + \u0026szlig; ln t\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.962\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.971\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eKorsmeyer-Peppas\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eM\u003csub\u003et\u003c/sub\u003e/M\u003csub\u003e\u0026infin;\u003c/sub\u003e= K.t\u003csup\u003en\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.952\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.934\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cb\u003eNote\u003c/b\u003e: k\u003csub\u003e0\u003c/sub\u003e, k\u003csub\u003ef\u003c/sub\u003e, and k\u003csub\u003eH\u003c/sub\u003e represent the drug release constants; t\u003csub\u003ed\u003c/sub\u003e denotes the timescale of the process, and F indicates the drug release fraction at time t.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u003ch2\u003e3.8. Cytotoxicity study\u003c/h2\u003e\u003cp\u003eTo evaluate the biocompatibility and cytotoxic potential of the synthesised composite, an MTT assay was performed using human lung adenocarcinoma cells (A549) [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR46\" citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. Cells were exposed to increasing concentrations (0.05\u0026ndash;4 mg/mL) of CMC/MIL-88B(Fe), DEX, and CMC/MIL-88B(Fe)/DEX for 48 h, and the cell viability percentages were determined relative to the untreated control (100%). As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e7\u003c/span\u003e, all concentrations exhibited a dose-dependent decrease in cell viability, indicating concentration-dependent cytotoxicity. The blank CMC/MIL-88B nanocomposite maintained more than 60% cell viability even at the highest tested concentration (4 mg/mL), confirming its good biocompatibility and negligible intrinsic cytotoxicity. This result suggests that the MOF\u0026ndash;polymer hybrid matrix of CMC/MIL-88B(Fe) is suitable for biomedical applications. In contrast, free DEX exhibited marked cytotoxicity toward A549 cells, with viability dropping to approximately 45% at 4 mg/mL, demonstrating the potent cellular response induced by the drug. Interestingly, the CMC/MIL-88B/DEX composite showed significantly lower cytotoxicity compared to free DEX at the same concentrations. This reduction in cytotoxicity can be attributed to the controlled and sustained release behaviour of DEX from the CMC/MIL-88B(Fe) matrix, which minimises the initial burst release and limits direct drug\u0026ndash;cell interactions. The structural integrity of the MIL-88B(Fe) framework, combined with the hydrophilic CMC coating, likely contributed to a slower drug diffusion rate and reduced acute toxicity. So, the results highlight the excellent cytocompatibility of the carrier and confirm that CMC/MIL-88B can serve as a safe and efficient platform for controlled dexamethasone delivery in A549 cells.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"4. Conclusions","content":"\u003cp\u003eIn this study, a novel pH-responsive and biocompatible CMC/MIL-88B(Fe) bio-nanocomposite was successfully synthesised and demonstrated to be an efficient carrier for the controlled delivery of dexamethasone. Structural and morphological characterisations confirmed the successful integration of MIL-88B(Fe) within the CMC matrix, forming a stable mesoporous framework with enhanced surface area and uniform particle distribution. The nanocomposite exhibited a high drug encapsulation efficiency (82.7%) and distinct pH-dependent release behaviour, releasing approximately 78% of DEX at acidic pH 5.0 and only 39% at physiological pH 7.4. This selective release confirms the system\u0026rsquo;s potential for targeted drug delivery under tumour-like conditions. The MTT assay on A549 lung carcinoma cells revealed that the CMC/MIL-88B(Fe) carrier was highly biocompatible, maintaining over 60% cell viability even at high concentrations, while DEX-loaded composite exhibited reduced cytotoxicity compared to free DEX due to sustained and controlled drug release. These findings demonstrate that integrating CMC with MIL-88B(Fe) enhances both structural stability and therapeutic performance while minimising burst release and drug-induced toxicity. Overall, the developed CMC/MIL-88B(Fe) composite offers a promising, eco-friendly, and effective platform for the controlled and localised delivery of corticosteroids such as dexamethasone, particularly in inflammatory or tumour microenvironments characterised by acidic conditions. Future studies could focus on in vivo evaluations and surface functionalization strategies to further optimise its targeted delivery potential and pharmacological efficacy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest in this study.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData and materials related to this study can be provided by request.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMohammad Reza Darparesh: Conceptualization, Methodology, Formal analysis, Validation, Resources, Investigation, Visualization, Writing - Original Draft, Writing - Review \u0026amp; Editing, Project administration. Ramin Karimian: Formal analysis, Writing - Review \u0026amp; Editing. Mohammad Reza Khodabakhshi: Supervision, Conceptualization, Validation, Writing - Original Draft, Writing - Review \u0026amp; Editing, Project administration.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to express their sincere gratitude to all colleagues and collaborators who contributed to this research. Their valuable assistance, insightful discussions, and technical support are greatly appreciated.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eChenxi Z, Hemmat A, Thi N, Afrand M. Nanoparticle-enhanced drug delivery systems: An up-to-date review. Journal of Molecular Liquids. 2025:126999. DOI: https://doi.org/10.1016/j.molliq.2025.126999\u003c/li\u003e\n\u003cli\u003eEzike TC, Okpala US, Onoja UL, Nwike CP, Ezeako EC, Okpara OJ, et al. 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Carboxymethyl cellulose/tetracycline@ UiO-66 nanocomposite hydrogel films as a potential antibacterial wound dressing. International Journal of Biological Macromolecules. 2021;188:811-9. DOI: https://doi.org/10.1016/j.ijbiomac.2021.08.061\u003c/li\u003e\n\u003cli\u003eLin Y-S, Lin K-S. Characterization of the size and porous temperature sensitivity of Pluronic F127‒Coated MIL‒88B (Fe) for drug release. Microporous and Mesoporous Materials. 2021;328:111456. DOI: https://doi.org/10.1016/j.micromeso.2021.111456\u003c/li\u003e\n\u003cli\u003eDarvishi S, Sadjadi S, Heravi M. Post-functionalized cellulose/metal-organic framework composite with sulfonic acid: An efficient, rapid and recyclable bio-based solid acid catalyst for the synthesis of 5-hydroxymethylfurfural. International Journal of Biological Macromolecules. 2024;281:135866. DOI: https://doi.org/10.1016/j.ijbiomac.2024.135866\u003c/li\u003e\n\u003cli\u003eJavanbakht S, Hemmati A, Namazi H, Heydari A. 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AAPS PharmSciTech. 2024;25(7):208. DOI: https://doi.org/10.1208/s12249-024-02922-7\u003c/li\u003e\n\u003cli\u003eCorsaro C, Neri G, Mezzasalma AM, Fazio E. Weibull modeling of controlled drug release from Ag-PMA nanosystems. Polymers. 2021;13(17):2897. DOI: https://doi.org/10.3390/polym13172897\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"RTL\"\u003e45. Hadi S, Winarno EK, Winarno H, Susanto S, Thian DA, Fansang MD, et al. Synthesis, Characterization and Antiproliferative Activity Test of Some Diphenyltin (IV) Hydroxybenzoates Against A549, MCF-7 and HeLa Human Cancer Cell Lines. Journal of Inorganic and Organometallic Polymers and Materials. 2024;34(7):2980-9. DOI: https://doi.org/10.1007/s10904-024-03042-2\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"RTL\"\u003e46. Bepari A, Niazi SK, Khaled Y, Shaikh MA, Shaikh FM, Al-Zharani M, et al. 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DOI: https://doi.org/10.1007/s10904-024-03172-7\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Scheme 1","content":"\u003cp\u003eScheme 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-inorganic-and-organometallic-polymers-and-materials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"joip","sideBox":"Learn more about [Journal of Inorganic and Organometallic Polymers and Materials](https://www.springer.com/journal/10904)","snPcode":"10904","submissionUrl":"https://submission.nature.com/new-submission/10904/3","title":"Journal of Inorganic and Organometallic Polymers and Materials","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Drug delivery system, Metal–organic framework, Carboxymethylcellulose, Bio-nanocomposite, Dexamethasone, pH-responsive release","lastPublishedDoi":"10.21203/rs.3.rs-8038732/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8038732/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe development of smart drug delivery systems (DDS) has become essential for improving therapeutic efficiency while minimising adverse effects. In this work, a biocompatible carboxymethylcellulose / metal-organic framework composite (CMC/MIL-88B(Fe)) was designed and synthesised through an ultrasound-assisted method to achieve controlled and pH-responsive delivery of dexamethasone (DEX). The obtained material was thoroughly characterised using FT-IR, XRD, TGA/DSC, N₂ adsorption\u0026ndash;desorption, and FE-SEM/EDX analyses, confirming the successful formation of MIL-88B(Fe) crystals uniformly distributed within the amorphous CMC network. The composite exhibited a mesoporous structure and good drug-loading performance, achieving an encapsulation efficiency of about 82.7%. In vitro release studies revealed distinct pH-dependent release behaviour, where nearly 78% of DEX was released at acidic pH 5.0 in 240 h compared to 39% at physiological pH 7.4. Drug release kinetics followed the Weibull model (R\u0026sup2; \u0026gt;0.96), indicating diffusion-controlled release. To evaluate the biocompatibility and cytotoxic potential, an MTT assay was performed using A549 human lung adenocarcinoma cells. Cells were treated with increasing concentrations (0.05\u0026ndash;4 mg/mL) of CMC/MIL-88B(Fe), DEX, and CMC/MIL-88B(Fe)/DEX for 48 h. The CMC/MIL-88B(Fe) maintained over 60% cell viability even at the highest concentration, confirming good biocompatibility and negligible intrinsic cytotoxicity. In contrast, free DEX reduced cell viability to about 45% at 4 mg/mL, while the CMC/MIL-88B(Fe)/DEX system exhibited lower cytotoxicity at the same dose, due to the controlled and sustained drug release from the hybrid matrix. These findings highlight the excellent cytocompatibility and controlled delivery performance of CMC/MIL-88B(Fe), making it a promising platform for safe and efficient corticosteroid delivery in inflammatory and tumour-related applications.\u003c/p\u003e","manuscriptTitle":"Synthesis and characterisation of a pH-responsive carboxymethylcellulose/metal-organic framework CMC/MIL-88B(Fe) bio-nanocomposite for controlled dexamethasone delivery","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-18 15:31:44","doi":"10.21203/rs.3.rs-8038732/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-11-10T13:55:30+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-10T09:22:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"77757370324435841664180118632553408028","date":"2025-11-10T07:04:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"336353518399092996076817875603167986716","date":"2025-11-10T04:40:20+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-10T02:16:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"181317199430016100754695291878407298055","date":"2025-11-09T14:41:57+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-09T13:36:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"23205119974471578199800968608089736024","date":"2025-11-09T12:56:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"69323586448890196380345874119072719566","date":"2025-11-09T11:51:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"156307448270698004408584198709490001507","date":"2025-11-09T11:35:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"282852098727915831960602991921302671561","date":"2025-11-09T11:33:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"115614951898380556985605042828243914163","date":"2025-11-09T11:28:49+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-09T11:23:33+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-08T18:42:46+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-08T02:09:46+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Inorganic and Organometallic Polymers and Materials","date":"2025-11-05T12:56:56+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-inorganic-and-organometallic-polymers-and-materials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"joip","sideBox":"Learn more about [Journal of Inorganic and Organometallic Polymers and Materials](https://www.springer.com/journal/10904)","snPcode":"10904","submissionUrl":"https://submission.nature.com/new-submission/10904/3","title":"Journal of Inorganic and Organometallic Polymers and Materials","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"a45f2ab8-004b-46cc-93f7-c3661258b996","owner":[],"postedDate":"November 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-22T16:05:08+00:00","versionOfRecord":{"articleIdentity":"rs-8038732","link":"https://doi.org/10.1007/s10904-025-04135-2","journal":{"identity":"journal-of-inorganic-and-organometallic-polymers-and-materials","isVorOnly":false,"title":"Journal of Inorganic and Organometallic Polymers and Materials"},"publishedOn":"2025-12-18 15:57:42","publishedOnDateReadable":"December 18th, 2025"},"versionCreatedAt":"2025-11-18 15:31:44","video":"","vorDoi":"10.1007/s10904-025-04135-2","vorDoiUrl":"https://doi.org/10.1007/s10904-025-04135-2","workflowStages":[]},"version":"v1","identity":"rs-8038732","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8038732","identity":"rs-8038732","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}