Development and in-vitro Assessment of Topical Gel of Celecoxib-Loaded Nanosponges for the Rheumatoid Arthritis

Development and in-vitro Assessment of Topical Gel of Celecoxib-Loaded Nanosponges for the Rheumatoid Arthritis | 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 Article Development and in-vitro Assessment of Topical Gel of Celecoxib-Loaded Nanosponges for the Rheumatoid Arthritis Saraswathi Tenpattinam Shanmugam, Sarad Pawar Naik Bukke, Preethi Natarajan, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6009743/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Osteoarthritis is characterised by degenerative changes, while rheumatoid arthritis is an inflammatory disorder characterised by swelling and inflammation in the synovial membranes of the joints, which leads to bone erosion and joint deformity. Although new drugs have expanded treatment options, severe rheumatoid arthritis can significantly impair physical functions. Methods Using Emulsion Solvent Evaporation technology with a 3 2 -factorial design. Various concentrations of ethyl-cellulose (EC) and poly-vinyl alcohol (PVA) as rate-inhibiting copolymers. The Nanosponges were also tested for particle size (PS), zeta potential (ZP), entrapment efficacy (EE), and drug loading. It was subjected to physicochemical characterisation using FT-IR, XRD, TEM and SEM. The Carbopol 934P gel was treated with an optimised CENS containing an equal amount of Celecoxib. The celecoxib-loaded NS gel was further tested for viscosity, spreadability, drug diffusion, stability, and skin irritation. Results CENS2 was constituted of Celecoxib, EC, and PVA, with particle size (259 ± 0.63nm), ZP (-7.01 ± 0.01 mV), and %EE (98.1%). The physicochemical tests of the produced NS showed polymer-drug compatibility, efficient drug encapsulation, and that the drug remained non-crystalline within the spherical NS. CENS3 topical gels revealed 86.3% drug diffusion in Franz cells after good drug release. Conclusion The current study suggests that a The CENS3-based gel could improve the transdermal delivery process without inducing skin irritation. Celecoxib Nanosponges gel could prove effective against Rheumatoid arthritis. Biological sciences/Drug discovery Health sciences/Rheumatology Celecoxib Nanosponges 3 2 full factorial design Optimization Anti-Inflammatory activity Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Introduction Nanomedicine is transforming medical research by means of nanoscale materials applied for surveillance, maintenance, development, and recovery of living systems. Recent use of nanotechnology by pharmaceutical professionals has produced efficient personalised drug delivery systems 1 – 3 . Several nanocarrier systems— metallic and polymeric nanoparticles, nano-suspensions, nanotubes, nanofibers, and nanosponges—have commercial uses in everyday products and are extensively used for the efficient treatment of infectious diseases 4 – 6 . NS enables disruption within application mechanisms, hence reducing the likelihood of failure or negative outcomes. Nanosponges offer several benefits (Fig. 1 ), including non-toxicity, thermal stability, improved solubility, a regulated release mechanism, and the capability for targeted medicinal delivery. Furthermore, disadvantages NS can only store tiny molecules, preferably those with a mass of around 500 Daltons; bigger molecules are impractical 7 – 9 . Nanocarriers augment topical delivery by enhancing penetration and promoting localised accumulation. These systems, offered in liquid, solid, and semisolid forms, are designed to deliver therapeutically effective drug concentrations to the skin or mucosal layers 10 – 12 . Rheumatoid arthritis is an inflammatory disorder marked by swelling and inflammation in the synovial membranes of the joints, resulting in bone erosion and joint deformity, unlike the degenerative alterations seen in osteoarthritis 13 – 15 . Despite the expansion of treatment options through new drugs, severe rheumatoid arthritis can considerably impair physical function 16 , 17 .. Celecoxib, a nonsteroidal anti-inflammatory medicine (NSAID), is employed to mitigate the symptoms of rheumatoid arthritis. It is beneficial in alleviating acute pain resulting from illnesses such as ankylosing spondylitis, juvenile rheumatoid arthritis in children over two years of age, and primary dysmenorrhea. Celecoxib selectively and noncompetitively inhibits COX-2, differentiating it from other NSAIDs. COX-2 is upregulated in inflammatory tissues as a result of inflammatory mediators. Celecoxib demonstrates a decreased effect on prostaglandin synthesis in the stomach mucosa relative to other NSAIDs, thereby lowering the risk of ulcer formation 18 , 19 . This research employed a 3² full factorial design to formulate celecoxib into nanosponges gel. The gel formulation utilising nanocarriers achieves deeper skin penetration compared to traditional topical semi-solid formulations, positioning it as a superior option for the effective treatment of rheumatoid arthritis. Materials and Methods Celecoxib was offered as a sample by Razi Pharmaceuticals Pvt. LTD. Ethyl cellulose, polyvinyl alcohol, dichloromethane, Carbopol 934P, and triethanolamine were acquired from Sisco Research Laboratories Pvt. Ltd. Molecular docking The enzyme cyclooxygenase 2 (PDB ID 5KIR) was utilised to retrieve the protein from the protein database. We utilised Autodock software version 6.2.1 for the optimisation and representation of the macromolecule prior to docking. The Protein Preparation Wizard facilitated the creation of macromolecules. Figure 2 illustrates the two-dimensional interactions of amino acids, while Fig. 3 depicts the three-dimensional docked complex. The ligand exhibited a score of 8.0 kcal, suggesting a robust interaction with the protein. Optimization and DOE A 3 2 full-factorial design was utilized to investigate the impacts of independent variables, specifically ethyl cellulose (EA) (X1) and polyvinyl alcohol (PVA) (X2). The particle size of nanosponges (Y1), entrapment efficiency (Y2), and percentage drug release (Y3) were optimised as dependent variables using DOE® 13.0 [Table 1 ] 20 . Formulation of Celecoxib Nanosponges The emulsion solvent evaporation technique was utilised for the development of nanosponges. Celecoxib and ethyl cellulose were incorporated with dichloromethane as the internal phase. Polyvinyl alcohol was dissolved in distilled water, which acted as the external phase, and then integrated into the pre-prepared internal phase combination. The mixture underwent magnetic churning for 2 hours at a velocity of 1000 rpm, as represented in Fig. 3 21,22 . The method was reproduced by adjusting the amounts of ethyl cellulose and polyvinyl alcohol as specified in Table 1 . Table 1 3 2 full factorial design with factors and levels Independent variables Levels -1 0 1 EC (X1) ratio 1 2.5 4 PVA (X2) ratio 1 4.5 8 Preparation Celecoxib Nanosponges gel formulation The gel matrix is formed by distributing a polymer in water and continually agitating it with a mechanical agitator. After preparing the gelling agent and Nanosponges, the mixture undergoes continuous agitation until a Nanosponges gel forms 23 , 24 . Evaluation of Celecoxib Nanosponges formulation Particle size dimensions, Zeta potential & Polydispersity index Mean size and dispersion, ZP, & PDI of produced Nanosponges was analysed utilizing the Instrument 25 . Entrapment Efficiency A specific quantity of CENS (10 mg) was combined with methanol, subjected to sonication for 15 minutes to disrupt the complexation, centrifuged, and the supernatant was filtered prior to thorough mixing for analysis using a UV-spectrophotometer at 253nm 26 . SEM analysis Morphology & surface characteristics of the synthesized NS were analysed by a Scanning electron microscope 27 . TEM analysis Size & morphology of NS were assessed using a TEM equipped with NIH image software. Samples were evenly spread onto copper grids and observed 28 . X-ray diffraction study Celecoxib & CENS were converted at room temperature utilizing a diffractometer. The patterns were captured by Ni-filtered Cu Kα radiation 29 . Evaluation of Celecoxib Nanosponges gel pH, Drug content, Viscosity & Spread ability The CENS topical gel was assessed for several tests that include pH, Drug content, Viscosity & Spread ability 28 . Diffusion study of Celecoxib Nanosponges gel Drug diffusion was performed via a Franz diffusion cell fitted with an artificial cellophane membrane. In this experiment, 1 g of topical gel containing CENS gel samples was placed in the donor compartment, while a pH 7.4 buffer solution was inserted into the receptor-chamber. A constant temperature of 37 ± 0.5°C was sustained via a magnetic stirrer functioning at 50rpm 28 . The samples were collected and examined via spectrophotometry at a wavelength of 253 nm. The quantity of released drug was assessed, and the cumulative amount of diffusion of over a time period were reported for all CENS formulations. Albumin denaturation assay Protein denaturation, a major factor in inflammation, was evaluated using the method developed by Mizushima and Kobayashi, with substantial changes by Sakata et al. This experiment involved the amalgamation of 500µL of 1% bovine serum albumin with differing amounts of the test chemical NS-2. Acetylsalicylic acid functioned as the positive control 30 . The percentage inhibition of protein denaturation was assessed after the experiment was conducted in triplicate. Statistical analytical data Data analysis was done using one way analysis of variance with Dennett’s test, with statistical significance considered at p ≤ 0.05. Triplicate assessments were conducted for all samples 29 . Stability study The stability of the CENS3 stuffed topical gel were calculated over a period of 45 days by uncover the samples to room temp (25 ± 2°C) and hasten conditions (50 ± 2°C, 75%RH) 23 . Results and Discussion Evaluation of Celecoxib Nanosponges formulation Experimental Design (DOE) The responses have been identified by the use of the following interactive statistical model and poly-nomial terms 13 : Y = β0 + β1 A + β2 A + β3 AB + β4 A2 + β5 B2 + β6 AB + β7 AB2 Tables 4 , 5 , and 6 present the ANOVA results, demonstrating that all models were statistically significant (p 0.05) were excluded from the equations, leading to: The relationship between the response model equation and particle size: Y 1 = β 0 + β 1 (A) + β 2 (B) + β 3 (AB) Particle size (nm) = -172.75000 * (A) + 187.88333 * (B) − 244.67500 * (AB) As a result, the model equation for %EE changed to: Y 2 = = β 0 + β 1 (A) + β 2 (B) Entrapment Efficiency = 76.13111–7.26500 * (A) + 16.98000 * (B) The model equation that connected the greatest percentage of drug release as a reaction at the eighth hour was as follows: Y 3 = β 0 + β 1 (A) + β 2 (B) + β 3 (AB) % Drug Release Maximum at 8th hour = + 47.15667–6.47000* (A) + 4.76667*(B) A positive sign for a component indicates a positive correlation or synergistic interaction with the responses, as indicated by the model equation previously provided. Conversely, a negative sign for the same factor indicates an antagonistic interaction. The experimental trials, the specified parameters, and their impact on the measured responses are demonstrated in Table 2 and Table 3 . Table 2 Factors for the preparations Factors Coded Values Actual Values (×10 − 2 M) Polyvinyl alcohol (A) -1 1 0 4.5 1 8 Ethyl cellulose (B) -1 1 0 2.5 1 4 The values for EC and PVA have been set at low 104 and high 1196, respectively, based on the profiler's results. Table 3 Composition of the 3 2 full factorial CENS with response parameters Formulations PS (nm) (Y1) EE (%) (Y2) DR (%) (Y3) CENS1 227 ± 0.63 51.2 ± 0.21 68.2 ± 0.66 CENS2 259 ± 0.67 98.01 ± 0.44 88.3 ± 0.13 CENS3 319 ± 0.56 95.3 ± 0.38 81.4 ± 0.22 CENS4 329 ± 0.61 93.6 ± 0.24 66.3 ± 0.21 CENS5 485 ± 0.73 62.4 ± 0.15 63.2 ± 0.24 CENS6 104 ± 0.51 41.2 ± 0.43 71.2 ± 0.29 CENS7 784 ± 0.66 73.8 ± 0.16 72.7 ± 0.23 CENS8 1093 ± 0.83 84.2 ± 0.42 79.2 ± 0.22 CENS9 1196 ± 0.89 53.6 ± 0.18 69.6 ± 0.68 * Mean ± SD (n = 3) Table 4 ANOVA results for Particle size Source Sum of Df Mean F-value p-value Particle size (nm) (2FI) Model 6.121E + 05 3 221719.8 5.51918 0.0454* A- Polyvinyl alcohol 2.209E + 05 1 200504.7 5.49492 0.0523 B- Ethyl cellulose 1.384E + 05 1 233709.5 4.10204 0.0894 AB 2.488E + 05 1 249845.1 2.49801 0.0342 * Significance R 2 Value – 0.7 Table 5 ANOVA results for Entrapment Efficiency Source Sum of df Mean F-value p-value % DR Max at 6th hr (Linear) Model 567.46 2 192.75 7.110 0.0294* A- Polyvinyl alcohol 222.934 1 246.95 8.822 0.0211 B-Ethyl cellulose 2.42 1 2.42 1.648 0.67842 * Significance R 2 Value – 0.81 Table 6 % Drug Release at 6th hours ANOVA results Source Sum of df Mean F-value p-value EE (Linear) Model 2379.315 5 467.80 55.76814 0.0034* A- Polyvinyl alcohol 361.1474 1 361.1492 42.61897 0.0061 B- Ethyl cellulose 1485.165 1 1465.165 185.26734 0.0006 * Significance R 2 Value – 0.98 The ANOVA results, as demonstrated in Tables 4 , 5 , and 6 , indicated that all models were statistically significant (p < 0.05). Models were simplified by eliminating non-significant terms (p < 0.05) from equations. Particle size All formulations are nanoscale, as evidenced by the particle diameters of nanosponges, which range from 227 to 1196 nm. Nonlinearity is evident in the initial four formulations with respect to particle size analysis. Formulations CENS7, CENS8, and CENS9 were excluded from nanosponges due to their micrometer particle sizes. Analysis of Variance (ANOVA) The statistical significance of Table 4 is shown by the 5.619 f-value. P-values below 0.0500, which is approximately 0.0468, are indicative of significant model variables. Consequently, the relevance of model component AB and the relationship between independent variables and the response (PS) are demonstrated. Entrapment Efficiency (EE) Critical to the efficacy of medications expressed by nanoparticles is their ability to rapidly reach their target sites of action. The Nanosponges were able to entrap a greater amount of substance due to the improved polymer cross-linking in CENS2, which resulted in a higher encapsulation efficiency than that of CENS3. The f-value of 56.768 in ANOVA Table 5 demonstrates the model significance. The p-value of 0.0037, which is less than 0.0500, supports the model parameters significance. In-vitro Drug Release A dialysis technique was employed to measure the cumulative in-vitro drug release in phosphate buffer at pH 7.4. The remaining predictors are maintained at a predetermined value. Ethyl cellulose and polyvinyl alcohol exhibit low (63.2) and high (88.3) values, respectively, as indicated by the prediction profiler's findings. The model f-value of 7.1 is indicative of its significance, as shown in ANOVA Table 6 . The model variables are significant, as evidenced by the p-value of 0.029, which is less than 0.0500. AB is a substantial model term in this scenario. The independent variables are the components of the AB interaction, as evidenced by the interaction graph. Zeta potential Upon examination of the formulations, it was evident that their potency levels were negative. The investigation concentrated on zeta potentials that ranged from − 3.96 ± 0.02 to 0.103 ± 0.002. Polydispersity index The polydispersity index is a measure of the degree of diversity in the distribution of particle sizes. The Nanosponges formulations that were tested all exhibited values in the center of the polydispersity index range, with the exception of formulations CENS7-CENS9, which adhered to the ranges depicted in the polydispersity index table. X-ray diffraction studies The XRD particle patterns of unadulterated celecoxib and the formulation of celecoxib nanosponges are compared in Fig. 4 . The crystalline structure of the compound may be indicated by the presence of individual and conspicuous peaks in the patterns of purified celecoxib. The medication's efficacy within the Nanosponges' nuclei is suggested by the peak suppression observed in the PXRD pattern of a sample of Celecoxib Nanosponges. SEM analysis Scanning electron microscopy (SEM) analysis of nanosponges, as depicted in Fig. 5 , revealed the presence of nanostructured particles composed of spherical and porous particles. The nanosponges' porous and sponge-like characteristics are evident in the image. The porous and flexible spongy characteristics of the NS were disclosed by SEM images. The inward migration of dichloromethane (DCM) into the ethyl cellulose (EC) polymeric surface during the production process is the most probable cause of these properties. TEM analysis The continuous size and shape of the nanosponges that were examined using transmission electron microscopy (TEM) are illustrated in Fig. 6 . The integrity of the nanosponges in the gel was not found to be affected by the studies that assessed their presence. Evaluation of Celecoxib Nanosponges gel formulation Viscosity, pH, Drug content and Spreadability After skin application, the celecoxib NS-based topical gel maintained an optimal pH of 6.02 ± 0.30. The study determined that CENS had a significantly high diffusion rate of 13.62 ± 0.75 g-cm/sec. The projected CENS was 35,000 to 40,000 cps and 98.27% in terms of viscosity and drug content. The rheological investigation demonstrated that the topical gel generated exhibited pseudoplastic flow characteristics as a result of shear thinning. The drug content analysis verified that the Nanosponges gel contained a homogeneous distribution of Celecoxib throughout, and the spreadability value indicated that the CENS2 gel was instantaneously applied to the afflicted skin region. Drug diffusion study The findings of the analysis indicated that the CENS2 gel formulation had a higher drug release percentage (90.06 percent) than the CENS3 formulation (89.2 percent). The observed discrepancy may be due to variations in the concentrations of EC and PVA in the formulations (Fig. 7 ). Effect of Ethyl Cellulose on EE and PA The entrapment efficiency and particle size of a product are significantly influenced by EC. Furthermore, ethyl cellulose serves as an emulsifier and provides stabilization. Higher EC values may result in reduced particle sizes due to enhanced surface activity and improved emulsion or dispersion stability. Formulation circumstances, manufacturing techniques, and the type and concentration of the active constituent are likely to influence entrapment efficiency and particle size. Effect of Polyvinyl alcohol on EE and PA Particle size and stability may be influenced by the impact of PVA on nanosponges. As the concentration of PVA increases, the size of the particles decreases. The ability of a gel to transition into a liquid phase is diminished by elevated PVA concentrations, which leads to more unyielding bilayers. The results indicated that the optimized product exhibited a higher drug release percentage, a smaller particle size, and a high drug encapsulation efficiency after six hours. Additionally, spherical vesicles were identified. The optimized formulation exhibited a 90.06% maximal drug release rate after 6 hours, a particle size of 319 nm, and a 98.03% encapsulation efficiency (Fig. 8 ). The surface response curve illustrates the proportional impact of various process parameters on the drug release percentage, entrapment efficiency, and particle size at the 6th h. Optimized formulation of Celecoxib Nanosponges After assessing each parameter, the final optimised formula was produced, as shown in Table 7 . Table 7 Optimized Nanosponges Formulation Factors Level Actual Values (×10 − 2 M) Polyvinyl alcohol 0.3072 2.5 Ethyl cellulose 0.7615 0.5 Dissolution data with Kinetic models Zero-order release kinetics are demonstrated by the optimized formulation. The graph implies that diffusion may regulate the discharge of nanosponges. In Table 8 , the "n" value of the CENS in the Korsmeyer-Peppas model was determined to be 0.98, indicating anomalous or Non-Fickian diffusion. Table 8 Optimized Celecoxib Nanosponges formulation Release Kinetic models Higuchi KorsemeyerPeppas Zero order First order Hixon-Crowell Formulation r² r² r² r² r² Optimized formulation 0.9772 0.9823 0.8891 0.9907 0.9906 Albumin Denaturation Assay The efficacy of bioactive compounds and CENS2 in reducing protein denaturation was evaluated in order to evaluate their ability to reduce inflammation. Figure 9 illustrates that CENS2 reduces protein denaturation in a dose-dependent manner, with values of 34.50 ± 3.9% at 50 µg/mL. At a concentration of 500 µg/mL, the denaturation of CENS2 was reduced by 84.89 ± 0.98%. The CENS gel formulation exhibited a greater anti-inflammatory potential than unmodified Celecoxib, as evidenced by the data in Table 9 . Therefore, the study's observed reduction in denaturation with CENS2 may suggest potential therapeutic implications for autoimmune illnesses and inflammation, including rheumatoid arthritis. Table 9 Inhibition % of Albumin denaturation (%) S. No Concentration of test samples (µg/ml) Inhibition % albumin denaturation (in triplicates) Mean Value (%) 1. 500 µg/ml 49.2104 48.0387 47.2236 48.1576 2. 250 µg/ml 43.2501 42.8935 41.569 42.5709 3. 100 µg/ml 41.5181 41.2634 40.8558 41.2124 4. 50 µg/ml 14.5695 13.7545 14.1111 14.145 5. 10 µg/ml 0 0 0 0 (mean ± SD) (n = 3), *Significance – p < 0.05 Stability study Table 10 displays the particle sizes that were observed prior to and after the exhaustive stability testing of the optimized CENS2 gel formulation. The values were 319 nm and 409 nm, respectively. The observed fluctuation may be attributed to the storage and absorption of Nanosponges (NS) within the gel; at this time, the particles were still within the nanoscale range. Table 10 Stability study of Celecoxib Nanosponges formulation Storage conditions Duration (month) Particle size (nm) Entrapment efficiency (%) 4ºC ± 1ºC 1 2 3 346 ± 30.18 351 ± 12.23 363 ± 25.29 98.03% 96.92% 94.39% 25ºC ± 2ºC/60 + 5% RH 1 2 3 322 ± 18.23 309 ± 30.13 296 ± 28.32 91.09% 87.53% 86.21% (mean ± SD) (n = 3) Conclusion The gel formulation with nanocarriers is a superior choice for treating rheumatoid arthritis due to its superior skin penetration compared to other topical semi-solid formulations. Nanocarriers facilitate the diffusion of pharmaceuticals more profoundly into the epidermal layers, thereby enhancing their pharmacological efficacy. The solvent emulsion diffusion process was employed to effectively develop celecoxib nanosponges (CENS1-CENS9), which reached nanoscale particle sizes as a result of the ethyl cellulose (EC) and polyvinyl alcohol (PVA) ratios. The 32 full factorial design was employed to achieve this. The polymer ratios employed have an impact on the physicochemical characteristics of nine Nanosponges that have been investigated for therapeutic purposes. Spherical nanosponges contain the medication. The stability, anti-inflammatory efficacy, and drug diffusion of all gel formulations were assessed using Franz diffusion cells. The results demonstrated significant anti-inflammatory efficacy, favorable release patterns, and excellent drug loading efficiency. The results indicate that the gel laden with celecoxib is effective, suggesting that it could be employed as a carrier for improved rheumatoid arthritis treatment. Abbreviations NS nanosponge EA Ethyl Cellulose PVA Polyvinyl alcohol DOE Experimental Design EE Entrapment Efficiency DCM diffusion of dichloromethane XRD X-ray diffraction SEM Scanning electron microscopy TEM Transmission electron microscopy. Declarations I hereby declare that this submission is entirely my own work, in my own words, and that all sources used in researching it are fully acknowledged and all quotations properly identified. Statement of Informed Consent There are no human subjects in this article and informed consent is not applicable. Consent to Publication All the authors have read and agreed to the final copy of the finding as contained in the manuscript. Availability of data and materials The datasets/information used for this study is available on reasonable request to the corresponding author. Conflicting interest All authors report that there was no conflict of interest in this work. Funding The author(s) received for funding this work through Large Research Project under grant number RGP2/530/45. Ethical approval Ethical Approval is not applicable for this article. Author Contribution Statement STS and SPNB initiated the conception. STS, SPNB and PN developed the design. STS, SPNB, PN, BRN and MAAA conducted the experiments. STS, SPNB and BRN analyzed the results. STS, SPNB, BRN and MAAA prepared the first draft of the manuscript. STS, SPNB, PN, BRN and MAAA reviewed and edited the manuscript. The authors read and approved the final manuscript. Acknowledgement The authors extend their appreciation to the Deanship of Research and Graduate Studies at King Khalid University for funding this work through Large Research Project under grant number RGP2/530/45. List of Abbreviations NS: nanosponge, EA: Ethyl Cellulose, PVA: Polyvinyl alcohol, DOE: Experimental Design, EE: Entrapment Efficiency, DCM: diffusion of dichloromethane, XRD: X-ray diffraction, SEM: Scanning electron microscopy, TEM: Transmission electron microscopy. References Sim, S. & Wong, N. Nanotechnology and its use in imaging and drug delivery (Review). Biomed. Rep. 14 , 42 (2021). Eldose, A. et al. Nanosponge: A Novel Nano Drug Carrier. J. Adv. Res. Pharm. Biol. Sci. 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Juvekar, A., Sakat, S., Wankhede, S., Juvekar, M. & Gambhire, M. Evaluation of antioxidant and anti-inflammatory activity of methanol extract of Oxalis corniculata. Planta Med. 75 , s–0029 (2009). Additional Declarations No competing interests reported. Supplementary Files floatimage1.jpeg Graphical abstract supplementaryfile1.docx supplementaryfile2.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6009743","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":415748173,"identity":"235d714e-0147-4313-a012-f2420a5a61e4","order_by":0,"name":"Saraswathi Tenpattinam Shanmugam","email":"","orcid":"","institution":"SRM College of Pharmacy, SRM Institute of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Saraswathi","middleName":"Tenpattinam","lastName":"Shanmugam","suffix":""},{"id":415748174,"identity":"90f41c39-9f78-420a-b6a1-3c2fb3a2c3ce","order_by":1,"name":"Sarad Pawar Naik Bukke","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA80lEQVRIiWNgGAWjYDCCA2CSGcL5cECCRC2MM0jWwsxzgAgdfLePP/xcUWOdxz8j+dlnmzMWiQ3shx8w8/zCrUXyXI6x5Jlj6cUSN9KMZ+fckEhs4EkzYObtw63F4AwPg2QD2+HEhtsJxsw5H4BaGHIYmHl78Glhf/yz4d/hxPm30z8zW4C08L8hpIXBTLKx7XDihts5xswMIIdJAG3h+YHHL2d4zCwb+9KLDe+/KWbsOSNh3CbxzODg3AbcWviADrvZ8M06T+7M8c0MP47VyfbzJz988OYPbi0wkABnsQHxAcY2UrRAABG2jIJRMApGwYgBAI0UVhgzbaM9AAAAAElFTkSuQmCC","orcid":"","institution":"Kampala International University","correspondingAuthor":true,"prefix":"","firstName":"Sarad","middleName":"Pawar Naik","lastName":"Bukke","suffix":""},{"id":415748175,"identity":"68dab926-7a7c-4bc7-bb96-0c1a85cfb491","order_by":2,"name":"Preethi Natarajan","email":"","orcid":"","institution":"SRM College of Pharmacy, SRM Institute of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Preethi","middleName":"","lastName":"Natarajan","suffix":""},{"id":415748176,"identity":"2e24edca-72df-42c0-9778-ac530c029d43","order_by":3,"name":"Bayapa Reddy Narapureddy","email":"","orcid":"","institution":"King Khalid University","correspondingAuthor":false,"prefix":"","firstName":"Bayapa","middleName":"Reddy","lastName":"Narapureddy","suffix":""},{"id":415748177,"identity":"0f8e57cd-ab16-4e80-ba6b-be657842da1b","order_by":4,"name":"Muhammad Ali Abdullah Almoyad","email":"","orcid":"","institution":"King Khalid University","correspondingAuthor":false,"prefix":"","firstName":"Muhammad","middleName":"Ali Abdullah","lastName":"Almoyad","suffix":""}],"badges":[],"createdAt":"2025-02-11 18:23:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6009743/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6009743/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":76475010,"identity":"61f5c3f1-ec5f-4174-a5f0-0694ecaa99ae","added_by":"auto","created_at":"2025-02-17 13:40:20","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":213166,"visible":true,"origin":"","legend":"\u003cp\u003eStructure of Nanosponges\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6009743/v1/6b8c99417ac4d6e5fb03cc8c.png"},{"id":76474986,"identity":"9f8d268f-4b6d-4855-a2c7-e89aa59c3228","added_by":"auto","created_at":"2025-02-17 13:40:17","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":122764,"visible":true,"origin":"","legend":"\u003cp\u003eAmino acid interactions in 2D and the docked complex in 3D image\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6009743/v1/1ecd96d7b127cb8a476a835e.png"},{"id":76474978,"identity":"4b7c6908-1b93-447c-b8bc-dc0caa6fc8a2","added_by":"auto","created_at":"2025-02-17 13:40:17","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":94879,"visible":true,"origin":"","legend":"\u003cp\u003ePreparation of Celecoxib Nanosponges\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6009743/v1/c38a059f8717d9d2b9b31980.jpeg"},{"id":76475571,"identity":"7119b71f-dee9-470c-ad5b-bf14df87a3a7","added_by":"auto","created_at":"2025-02-17 13:48:17","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":24186,"visible":true,"origin":"","legend":"\u003cp\u003eXRD graph of (1) Pure Celecoxib (2) Celecoxib Nanosponges\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-6009743/v1/1d193ef92e19d0b1c354de33.png"},{"id":76474981,"identity":"61beb617-2245-4281-8d0b-d9df5547735e","added_by":"auto","created_at":"2025-02-17 13:40:17","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":67282,"visible":true,"origin":"","legend":"\u003cp\u003eScanning electron microscopy image of Celecoxib Nanosponges\u003c/p\u003e","description":"","filename":"floatimage7.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6009743/v1/b7c44097b6239e5e4d2f0efb.jpeg"},{"id":76474991,"identity":"79567c44-6f66-499b-be5c-88c66532de7d","added_by":"auto","created_at":"2025-02-17 13:40:18","extension":"jpeg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":237996,"visible":true,"origin":"","legend":"\u003cp\u003eTransmission electron microscopy images of Celecoxib -loaded Nanosponges\u003c/p\u003e","description":"","filename":"floatimage8.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6009743/v1/1c24f9a42c4e429817f50edb.jpeg"},{"id":76474975,"identity":"8990a92b-620a-4eb0-82b7-296fa8cdc7ac","added_by":"auto","created_at":"2025-02-17 13:40:17","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":74419,"visible":true,"origin":"","legend":"\u003cp\u003e% Drug release of Celecoxib Nanosponges Gel\u003c/p\u003e","description":"","filename":"floatimage9.png","url":"https://assets-eu.researchsquare.com/files/rs-6009743/v1/e72f37fa8ea85241799a32e3.png"},{"id":76474984,"identity":"0c52f5be-5736-4144-89b0-cfc66d008dd0","added_by":"auto","created_at":"2025-02-17 13:40:17","extension":"jpeg","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":375856,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Particle Size, (B) Entrapment Efficiency, and (C) Percentage drug release\u003c/p\u003e","description":"","filename":"floatimage10.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6009743/v1/4aeab927ebea5c461d40c972.jpeg"},{"id":76475576,"identity":"09146bce-2356-41b0-af41-ddb6ebf12bfd","added_by":"auto","created_at":"2025-02-17 13:48:17","extension":"jpeg","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":452616,"visible":true,"origin":"","legend":"\u003cp\u003ePercentage of Inhibition of Optimized formulation\u003c/p\u003e","description":"","filename":"floatimage11.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6009743/v1/87f972f809f2585f51eaab6f.jpeg"},{"id":77201183,"identity":"759db840-2685-40c5-b1a8-45f5c706e7ad","added_by":"auto","created_at":"2025-02-26 07:32:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3114658,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6009743/v1/603b4ef7-bbb1-423e-9531-23b455e32ff9.pdf"},{"id":76475572,"identity":"0f44eebc-aaf4-4566-8ba4-c65bde30914c","added_by":"auto","created_at":"2025-02-17 13:48:17","extension":"jpeg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":498790,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGraphical abstract\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6009743/v1/658c4b4aeac02a01c70e5800.jpeg"},{"id":76474979,"identity":"b9dbab59-0ff1-4d8b-9f0a-5e405f05df82","added_by":"auto","created_at":"2025-02-17 13:40:17","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":477248,"visible":true,"origin":"","legend":"","description":"","filename":"supplementaryfile1.docx","url":"https://assets-eu.researchsquare.com/files/rs-6009743/v1/3b21c264cbeaf1348d32a464.docx"},{"id":76474982,"identity":"f1952913-150c-495b-9f41-d6f19e4b8030","added_by":"auto","created_at":"2025-02-17 13:40:17","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":468169,"visible":true,"origin":"","legend":"","description":"","filename":"supplementaryfile2.docx","url":"https://assets-eu.researchsquare.com/files/rs-6009743/v1/5a8a68b209336a85393c9ef9.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Development and in-vitro Assessment of Topical Gel of Celecoxib-Loaded Nanosponges for the Rheumatoid Arthritis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eNanomedicine is transforming medical research by means of nanoscale materials applied for surveillance, maintenance, development, and recovery of living systems. Recent use of nanotechnology by pharmaceutical professionals has produced efficient personalised drug delivery systems \u003csup\u003e\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Several nanocarrier systems\u0026mdash; metallic and polymeric nanoparticles, nano-suspensions, nanotubes, nanofibers, and nanosponges\u0026mdash;have commercial uses in everyday products and are extensively used for the efficient treatment of infectious diseases \u003csup\u003e\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eNS enables disruption within application mechanisms, hence reducing the likelihood of failure or negative outcomes. Nanosponges offer several benefits (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), including non-toxicity, thermal stability, improved solubility, a regulated release mechanism, and the capability for targeted medicinal delivery. Furthermore, disadvantages NS can only store tiny molecules, preferably those with a mass of around 500 Daltons; bigger molecules are impractical \u003csup\u003e\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eNanocarriers augment topical delivery by enhancing penetration and promoting localised accumulation. These systems, offered in liquid, solid, and semisolid forms, are designed to deliver therapeutically effective drug concentrations to the skin or mucosal layers \u003csup\u003e\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eRheumatoid arthritis is an inflammatory disorder marked by swelling and inflammation in the synovial membranes of the joints, resulting in bone erosion and joint deformity, unlike the degenerative alterations seen in osteoarthritis \u003csup\u003e\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Despite the expansion of treatment options through new drugs, severe rheumatoid arthritis can considerably impair physical function \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e..\u003c/p\u003e \u003cp\u003eCelecoxib, a nonsteroidal anti-inflammatory medicine (NSAID), is employed to mitigate the symptoms of rheumatoid arthritis. It is beneficial in alleviating acute pain resulting from illnesses such as ankylosing spondylitis, juvenile rheumatoid arthritis in children over two years of age, and primary dysmenorrhea. Celecoxib selectively and noncompetitively inhibits COX-2, differentiating it from other NSAIDs. COX-2 is upregulated in inflammatory tissues as a result of inflammatory mediators. Celecoxib demonstrates a decreased effect on prostaglandin synthesis in the stomach mucosa relative to other NSAIDs, thereby lowering the risk of ulcer formation \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThis research employed a 3\u0026sup2; full factorial design to formulate celecoxib into nanosponges gel. The gel formulation utilising nanocarriers achieves deeper skin penetration compared to traditional topical semi-solid formulations, positioning it as a superior option for the effective treatment of rheumatoid arthritis.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eCelecoxib was offered as a sample by Razi Pharmaceuticals Pvt. LTD. Ethyl cellulose, polyvinyl alcohol, dichloromethane, Carbopol 934P, and triethanolamine were acquired from Sisco Research Laboratories Pvt. Ltd.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eMolecular docking\u003c/h2\u003e \u003cp\u003eThe enzyme cyclooxygenase 2 (PDB ID 5KIR) was utilised to retrieve the protein from the protein database. We utilised Autodock software version 6.2.1 for the optimisation and representation of the macromolecule prior to docking. The Protein Preparation Wizard facilitated the creation of macromolecules. Figure\u0026nbsp;2 illustrates the two-dimensional interactions of amino acids, while Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003e depicts the three-dimensional docked complex. The ligand exhibited a score of 8.0 kcal, suggesting a robust interaction with the protein.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eOptimization and DOE\u003c/h3\u003e\n\u003cp\u003eA 3\u003csup\u003e2\u003c/sup\u003e full-factorial design was utilized to investigate the impacts of independent variables, specifically ethyl cellulose (EA) (X1) and polyvinyl alcohol (PVA) (X2). The particle size of nanosponges (Y1), entrapment efficiency (Y2), and percentage drug release (Y3) were optimised as dependent variables using DOE\u0026reg; 13.0 [Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e] \u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n\u003ch3\u003eFormulation of Celecoxib Nanosponges\u003c/h3\u003e\n \u003cp\u003eThe emulsion solvent evaporation technique was utilised for the development of nanosponges. Celecoxib and ethyl cellulose were incorporated with dichloromethane as the internal phase. Polyvinyl alcohol was dissolved in distilled water, which acted as the external phase, and then integrated into the pre-prepared internal phase combination. The mixture underwent magnetic churning for 2 hours at a velocity of 1000 rpm, as represented in Fig.\u0026nbsp;3 \u003csup\u003e21,22\u003c/sup\u003e. The method was reproduced by adjusting the amounts of ethyl cellulose and polyvinyl alcohol as specified in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\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\u003e3\u003csup\u003e2\u003c/sup\u003e full factorial design with factors and levels\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndependent variables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLevels\u003c/p\u003e \u003cp\u003e-1 0 1\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEC (X1) ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 2.5 4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePVA (X2) ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 4.5 8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003ePreparation Celecoxib Nanosponges gel formulation\u003c/h3\u003e\n \u003cp\u003eThe gel matrix is formed by distributing a polymer in water and continually agitating it with a mechanical agitator. After preparing the gelling agent and Nanosponges, the mixture undergoes continuous agitation until a Nanosponges gel forms \u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n\u003ch3\u003eEvaluation of Celecoxib Nanosponges formulation\u003c/h3\u003e\n \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eParticle size dimensions, Zeta potential \u0026amp; Polydispersity index\u003c/h2\u003e \u003cp\u003eMean size and dispersion, ZP, \u0026amp; PDI of produced Nanosponges was analysed utilizing the Instrument \u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEntrapment Efficiency\u003c/h3\u003e\n\u003cp\u003eA specific quantity of CENS (10 mg) was combined with methanol, subjected to sonication for 15 minutes to disrupt the complexation, centrifuged, and the supernatant was filtered prior to thorough mixing for analysis using a UV-spectrophotometer at 253nm \u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n\u003ch3\u003eSEM analysis\u003c/h3\u003e\n\u003cp\u003eMorphology \u0026amp; surface characteristics of the synthesized NS were analysed by a Scanning electron microscope \u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eTEM analysis\u003c/h2\u003e \u003cp\u003eSize \u0026amp; morphology of NS were assessed using a TEM equipped with NIH image software. Samples were evenly spread onto copper grids and observed \u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eX-ray diffraction study\u003c/h2\u003e \u003cp\u003eCelecoxib \u0026amp; CENS were converted at room temperature utilizing a diffractometer. The patterns were captured by Ni-filtered Cu Kα radiation \u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eEvaluation of Celecoxib Nanosponges gel pH, Drug content, Viscosity \u0026amp; Spread ability\u003c/h2\u003e \u003cp\u003eThe CENS topical gel was assessed for several tests that include pH, Drug content, Viscosity \u0026amp; Spread ability \u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eDiffusion study of Celecoxib Nanosponges gel\u003c/h2\u003e \u003cp\u003eDrug diffusion was performed via a Franz diffusion cell fitted with an artificial cellophane membrane. In this experiment, 1 g of topical gel containing CENS gel samples was placed in the donor compartment, while a pH 7.4 buffer solution was inserted into the receptor-chamber. A constant temperature of 37\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u0026deg;C was sustained via a magnetic stirrer functioning at 50rpm \u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. The samples were collected and examined via spectrophotometry at a wavelength of 253 nm. The quantity of released drug was assessed, and the cumulative amount of diffusion of over a time period were reported for all CENS formulations.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eAlbumin denaturation assay\u003c/h2\u003e \u003cp\u003eProtein denaturation, a major factor in inflammation, was evaluated using the method developed by Mizushima and Kobayashi, with substantial changes by Sakata et al. This experiment involved the amalgamation of 500\u0026micro;L of 1% bovine serum albumin with differing amounts of the test chemical NS-2. Acetylsalicylic acid functioned as the positive control \u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. The percentage inhibition of protein denaturation was assessed after the experiment was conducted in triplicate.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analytical data\u003c/h2\u003e \u003cp\u003eData analysis was done using one way analysis of variance with Dennett\u0026rsquo;s test, with statistical significance considered at p\u0026thinsp;\u0026le;\u0026thinsp;0.05. Triplicate assessments were conducted for all samples \u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eStability study\u003c/h2\u003e \u003cp\u003eThe stability of the CENS3 stuffed topical gel were calculated over a period of 45 days by uncover the samples to room temp (25\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u0026deg;C) and hasten conditions (50\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u0026deg;C, 75%RH) \u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results and Discussion","content":"\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eEvaluation of Celecoxib Nanosponges formulation\u003c/b\u003e\u003c/h2\u003e \u003cdiv id=\"Sec20\" class=\"Section3\"\u003e \u003ch2\u003eExperimental Design (DOE)\u003c/h2\u003e \u003cp\u003eThe responses have been identified by the use of the following interactive statistical model\u003c/p\u003e \u003cp\u003eand poly-nomial terms \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e:\u003c/p\u003e \u003cp\u003eY\u0026thinsp;=\u0026thinsp;β0\u0026thinsp;+\u0026thinsp;β1 A\u0026thinsp;+\u0026thinsp;β2 A\u0026thinsp;+\u0026thinsp;β3 AB\u0026thinsp;+\u0026thinsp;β4 A2\u0026thinsp;+\u0026thinsp;β5 B2\u0026thinsp;+\u0026thinsp;β6 AB\u0026thinsp;+\u0026thinsp;β7 AB2\u003c/p\u003e \u003cp\u003eTables\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, and \u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e present the ANOVA results, demonstrating that all models were statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) overall. To simplify the models, non-significant components (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) were excluded from the equations, leading to:\u003c/p\u003e \u003cp\u003eThe relationship between the response model equation and particle size:\u003c/p\u003e \u003cp\u003eY 1\u0026thinsp;=\u0026thinsp;β 0\u0026thinsp;+\u0026thinsp;β 1 (A) + β 2 (B) + β 3 (AB)\u003c/p\u003e \u003cp\u003eParticle size (nm) = -172.75000 * (A)\u0026thinsp;+\u0026thinsp;187.88333 * (B) \u0026minus;\u0026thinsp;244.67500 * (AB)\u003c/p\u003e \u003cp\u003eAs a result, the model equation for %EE changed to:\u003c/p\u003e \u003cp\u003eY 2 = = β 0\u0026thinsp;+\u0026thinsp;β 1 (A) + β 2 (B)\u003c/p\u003e \u003cp\u003eEntrapment Efficiency\u0026thinsp;=\u0026thinsp;76.13111\u0026ndash;7.26500 * (A)\u0026thinsp;+\u0026thinsp;16.98000 * (B)\u003c/p\u003e \u003cp\u003eThe model equation that connected the greatest percentage of drug release as a reaction at the eighth hour was as follows:\u003c/p\u003e \u003cp\u003eY 3\u0026thinsp;=\u0026thinsp;β 0\u0026thinsp;+\u0026thinsp;β 1 (A) + β 2 (B) + β 3 (AB)\u003c/p\u003e \u003cp\u003e% Drug Release Maximum at 8th hour\u0026thinsp;=\u0026thinsp;+\u0026thinsp;47.15667\u0026ndash;6.47000* (A)\u0026thinsp;+\u0026thinsp;4.76667*(B)\u003c/p\u003e \u003cp\u003eA positive sign for a component indicates a positive correlation or synergistic interaction with the responses, as indicated by the model equation previously provided. Conversely, a negative sign for the same factor indicates an antagonistic interaction. The experimental trials, the specified parameters, and their impact on the measured responses are demonstrated in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFactors for the preparations\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFactors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCoded Values\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eActual Values (\u0026times;10\u0026thinsp;\u0026minus;\u0026thinsp;2 M)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ePolyvinyl alcohol (A)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eEthyl cellulose (B)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe values for EC and PVA have been set at low 104 and high 1196, respectively, based on the profiler's results.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComposition of the 3\u003csup\u003e2\u003c/sup\u003e full factorial CENS with response parameters\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=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFormulations\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePS (nm) (Y1)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEE (%) (Y2)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDR (%) (Y3)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCENS1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e227\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e51.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e68.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.66\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCENS2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e259\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e98.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e88.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCENS3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e319\u0026thinsp;\u0026plusmn;\u0026thinsp;0.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e95.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e81.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCENS4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e329\u0026thinsp;\u0026plusmn;\u0026thinsp;0.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e93.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e66.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCENS5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e485\u0026thinsp;\u0026plusmn;\u0026thinsp;0.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e62.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e63.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCENS6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e104\u0026thinsp;\u0026plusmn;\u0026thinsp;0.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e41.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e71.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCENS7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e784\u0026thinsp;\u0026plusmn;\u0026thinsp;0.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e73.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e72.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCENS8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1093\u0026thinsp;\u0026plusmn;\u0026thinsp;0.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e84.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e79.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCENS9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1196\u0026thinsp;\u0026plusmn;\u0026thinsp;0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e53.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e69.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e* Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (n\u0026thinsp;=\u0026thinsp;3)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eANOVA results for Particle size\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSource\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSum of\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDf\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eF-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eParticle size (nm) (2FI)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.121E\u0026thinsp;+\u0026thinsp;05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e221719.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.51918\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.0454*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA- Polyvinyl alcohol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.209E\u0026thinsp;+\u0026thinsp;05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e200504.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.49492\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0523\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB- Ethyl cellulose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.384E\u0026thinsp;+\u0026thinsp;05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e233709.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.10204\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0894\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.488E\u0026thinsp;+\u0026thinsp;05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e249845.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.49801\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0342\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e* Significance\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eR\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Value \u0026ndash; 0.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eANOVA results for Entrapment Efficiency\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSource\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSum of\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003edf\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eF-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e% DR Max at 6th hr (Linear)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e567.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e192.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.0294*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA- Polyvinyl alcohol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e222.934\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e246.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.822\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0211\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB-Ethyl cellulose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.648\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.67842\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e* Significance\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eR\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Value \u0026ndash; 0.81\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e% Drug Release at 6th hours ANOVA results\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSource\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSum of\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003edf\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eF-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eEE (Linear)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2379.315\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e467.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e55.76814\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.0034*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA- Polyvinyl alcohol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e361.1474\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e361.1492\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42.61897\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0061\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB- Ethyl cellulose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1485.165\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1465.165\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e185.26734\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e* Significance\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eR\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Value \u0026ndash; 0.98\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe ANOVA results, as demonstrated in Tables \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, and \u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e, indicated that all models were statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Models were simplified by eliminating non-significant terms (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) from equations.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eParticle size\u003c/h2\u003e \u003cp\u003eAll formulations are nanoscale, as evidenced by the particle diameters of nanosponges, which range from 227 to 1196 nm. Nonlinearity is evident in the initial four formulations with respect to particle size analysis. Formulations CENS7, CENS8, and CENS9 were excluded from nanosponges due to their micrometer particle sizes.\u003c/p\u003e \u003cp\u003eAnalysis of Variance (ANOVA) The statistical significance of Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e is shown by the 5.619 f-value. P-values below 0.0500, which is approximately 0.0468, are indicative of significant model variables. Consequently, the relevance of model component AB and the relationship between independent variables and the response (PS) are demonstrated.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eEntrapment Efficiency (EE)\u003c/h2\u003e \u003cp\u003eCritical to the efficacy of medications expressed by nanoparticles is their ability to rapidly reach their target sites of action. The Nanosponges were able to entrap a greater amount of substance due to the improved polymer cross-linking in CENS2, which resulted in a higher encapsulation efficiency than that of CENS3. The f-value of 56.768 in ANOVA Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e demonstrates the model significance. The p-value of 0.0037, which is less than 0.0500, supports the model parameters significance.\u003c/p\u003e \u003cp\u003e \u003cb\u003eIn-vitro\u003c/b\u003e \u003cb\u003eDrug Release\u003c/b\u003e\u003c/p\u003e \u003cp\u003eA dialysis technique was employed to measure the cumulative \u003cem\u003ein-vitro\u003c/em\u003e drug release in phosphate buffer at pH 7.4. The remaining predictors are maintained at a predetermined value. Ethyl cellulose and polyvinyl alcohol exhibit low (63.2) and high (88.3) values, respectively, as indicated by the prediction profiler's findings. The model f-value of 7.1 is indicative of its significance, as shown in ANOVA Table \u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e. The model variables are significant, as evidenced by the p-value of 0.029, which is less than 0.0500. AB is a substantial model term in this scenario. The independent variables are the components of the AB interaction, as evidenced by the interaction graph.\u003c/p\u003e \u003cdiv id=\"Sec23\" class=\"Section3\"\u003e \u003ch2\u003eZeta potential\u003c/h2\u003e \u003cp\u003eUpon examination of the formulations, it was evident that their potency levels were negative. The investigation concentrated on zeta potentials that ranged from \u0026minus;\u0026thinsp;3.96\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02 to 0.103\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec24\" class=\"Section2\"\u003e \u003ch2\u003ePolydispersity index\u003c/h2\u003e \u003cp\u003eThe polydispersity index is a measure of the degree of diversity in the distribution of particle sizes. The Nanosponges formulations that were tested all exhibited values in the center of the polydispersity index range, with the exception of formulations CENS7-CENS9, which adhered to the ranges depicted in the polydispersity index table.\u003c/p\u003e \u003cdiv id=\"Sec25\" class=\"Section3\"\u003e \u003ch2\u003eX-ray diffraction studies\u003c/h2\u003e \u003cp\u003eThe XRD particle patterns of unadulterated celecoxib and the formulation of celecoxib nanosponges are compared in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003e. The crystalline structure of the compound may be indicated by the presence of individual and conspicuous peaks in the patterns of purified celecoxib. The medication's efficacy within the Nanosponges' nuclei is suggested by the peak suppression observed in the PXRD pattern of a sample of Celecoxib Nanosponges.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec26\" class=\"Section3\"\u003e \u003ch2\u003eSEM analysis\u003c/h2\u003e \u003cp\u003eScanning electron microscopy (SEM) analysis of nanosponges, as depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e5\u003c/span\u003e, revealed the presence of nanostructured particles composed of spherical and porous particles. The nanosponges' porous and sponge-like characteristics are evident in the image. The porous and flexible spongy characteristics of the NS were disclosed by SEM images. The inward migration of dichloromethane (DCM) into the ethyl cellulose (EC) polymeric surface during the production process is the most probable cause of these properties.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec27\" class=\"Section3\"\u003e \u003ch2\u003eTEM analysis\u003c/h2\u003e \u003cp\u003eThe continuous size and shape of the nanosponges that were examined using transmission electron microscopy (TEM) are illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e6\u003c/span\u003e. The integrity of the nanosponges in the gel was not found to be affected by the studies that assessed their presence.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec28\" class=\"Section2\"\u003e \u003ch2\u003eEvaluation of Celecoxib Nanosponges gel formulation\u003c/h2\u003e \u003cdiv id=\"Sec29\" class=\"Section3\"\u003e \u003ch2\u003eViscosity, pH, Drug content and Spreadability\u003c/h2\u003e \u003cp\u003eAfter skin application, the celecoxib NS-based topical gel maintained an optimal pH of 6.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.30. The study determined that CENS had a significantly high diffusion rate of 13.62\u0026thinsp;\u0026plusmn;\u0026thinsp;0.75 g-cm/sec. The projected CENS was 35,000 to 40,000 cps and 98.27% in terms of viscosity and drug content. The rheological investigation demonstrated that the topical gel generated exhibited pseudoplastic flow characteristics as a result of shear thinning. The drug content analysis verified that the Nanosponges gel contained a homogeneous distribution of Celecoxib throughout, and the spreadability value indicated that the CENS2 gel was instantaneously applied to the afflicted skin region.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e\n\u003ch3\u003eDrug diffusion study\u003c/h3\u003e\n\u003cp\u003eThe findings of the analysis indicated that the CENS2 gel formulation had a higher drug release percentage (90.06 percent) than the CENS3 formulation (89.2 percent). The observed discrepancy may be due to variations in the concentrations of EC and PVA in the formulations (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec31\" class=\"Section2\"\u003e \u003ch2\u003eEffect of Ethyl Cellulose on EE and PA\u003c/h2\u003e \u003cp\u003eThe entrapment efficiency and particle size of a product are significantly influenced by EC. Furthermore, ethyl cellulose serves as an emulsifier and provides stabilization. Higher EC values may result in reduced particle sizes due to enhanced surface activity and improved emulsion or dispersion stability. Formulation circumstances, manufacturing techniques, and the type and concentration of the active constituent are likely to influence entrapment efficiency and particle size.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec32\" class=\"Section2\"\u003e \u003ch2\u003eEffect of Polyvinyl alcohol on EE and PA\u003c/h2\u003e \u003cp\u003eParticle size and stability may be influenced by the impact of PVA on nanosponges. As the concentration of PVA increases, the size of the particles decreases. The ability of a gel to transition into a liquid phase is diminished by elevated PVA concentrations, which leads to more unyielding bilayers. The results indicated that the optimized product exhibited a higher drug release percentage, a smaller particle size, and a high drug encapsulation efficiency after six hours. Additionally, spherical vesicles were identified. The optimized formulation exhibited a 90.06% maximal drug release rate after 6 hours, a particle size of 319 nm, and a 98.03% encapsulation efficiency (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe surface response curve illustrates the proportional impact of various process parameters on the drug release percentage, entrapment efficiency, and particle size at the 6th h.\u003c/p\u003e \u003cdiv id=\"Sec33\" class=\"Section3\"\u003e \u003ch2\u003eOptimized formulation of Celecoxib Nanosponges\u003c/b\u003e\u003c/h2\u003e \u003cp\u003eAfter assessing each parameter, the final optimised formula was produced, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOptimized Nanosponges Formulation\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFactors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLevel\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eActual Values (\u0026times;10\u003csup\u003e\u0026minus;\u0026thinsp;2\u003c/sup\u003e M)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePolyvinyl alcohol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.3072\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEthyl cellulose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.7615\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec34\" class=\"Section3\"\u003e \u003ch2\u003eDissolution data with Kinetic models\u003c/h2\u003e \u003cp\u003eZero-order release kinetics are demonstrated by the optimized formulation. The graph implies that diffusion may regulate the discharge of nanosponges. In Table\u0026nbsp;\u003cspan refid=\"Tab8\" class=\"InternalRef\"\u003e8\u003c/span\u003e, the \"n\" value of the CENS in the Korsmeyer-Peppas model was determined to be 0.98, indicating anomalous or Non-Fickian diffusion.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab8\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 8\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOptimized Celecoxib Nanosponges formulation Release\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKinetic models\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHiguchi\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eKorsemeyerPeppas\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eZero order\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFirst order\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHixon-Crowell\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFormulation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003er\u0026sup2;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003er\u0026sup2;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003er\u0026sup2;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003er\u0026sup2;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003er\u0026sup2;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOptimized formulation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.9772\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9823\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.8891\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.9907\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.9906\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e\n\u003ch3\u003eAlbumin Denaturation Assay\u003c/h3\u003e\n\u003cp\u003eThe efficacy of bioactive compounds and CENS2 in reducing protein denaturation was evaluated in order to evaluate their ability to reduce inflammation. Figure\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e9\u003c/span\u003e illustrates that CENS2 reduces protein denaturation in a dose-dependent manner, with values of 34.50\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9% at 50 \u0026micro;g/mL. At a concentration of 500 \u0026micro;g/mL, the denaturation of CENS2 was reduced by 84.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.98%. The CENS gel formulation exhibited a greater anti-inflammatory potential than unmodified Celecoxib, as evidenced by the data in Table\u0026nbsp;\u003cspan refid=\"Tab9\" class=\"InternalRef\"\u003e9\u003c/span\u003e. Therefore, the study's observed reduction in denaturation with CENS2 may suggest potential therapeutic implications for autoimmune illnesses and inflammation, including rheumatoid arthritis.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab9\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 9\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eInhibition % of Albumin denaturation (%)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eS. No\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eConcentration of test samples (\u0026micro;g/ml)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eInhibition % albumin denaturation\u003c/p\u003e \u003cp\u003e(in triplicates)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMean Value (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e500 \u0026micro;g/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49.2104\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48.0387\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e47.2236\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e48.1576\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e250 \u0026micro;g/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43.2501\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42.8935\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e41.569\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e42.5709\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100 \u0026micro;g/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41.5181\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41.2634\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40.8558\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e41.2124\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 \u0026micro;g/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.5695\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.7545\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.1111\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14.145\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 \u0026micro;g/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD) (n\u0026thinsp;=\u0026thinsp;3), *Significance \u0026ndash; p\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eStability study\u003c/h3\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab10\" class=\"InternalRef\"\u003e10\u003c/span\u003e displays the particle sizes that were observed prior to and after the exhaustive stability testing of the optimized CENS2 gel formulation. The values were 319 nm and 409 nm, respectively. The observed fluctuation may be attributed to the storage and absorption of Nanosponges (NS) within the gel; at this time, the particles were still within the nanoscale range.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab10\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 10\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eStability study of Celecoxib Nanosponges formulation\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=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStorage conditions\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDuration (month)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eParticle size (nm)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEntrapment efficiency (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u0026ordm;C\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u0026ordm;C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e346\u0026thinsp;\u0026plusmn;\u0026thinsp;30.18\u003c/p\u003e \u003cp\u003e351\u0026thinsp;\u0026plusmn;\u0026thinsp;12.23\u003c/p\u003e \u003cp\u003e363\u0026thinsp;\u0026plusmn;\u0026thinsp;25.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e98.03%\u003c/p\u003e \u003cp\u003e96.92%\u003c/p\u003e \u003cp\u003e94.39%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25\u0026ordm;C\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u0026ordm;C/60\u0026thinsp;+\u0026thinsp;5% RH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e322\u0026thinsp;\u0026plusmn;\u0026thinsp;18.23\u003c/p\u003e \u003cp\u003e309\u0026thinsp;\u0026plusmn;\u0026thinsp;30.13\u003c/p\u003e \u003cp\u003e296\u0026thinsp;\u0026plusmn;\u0026thinsp;28.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e91.09%\u003c/p\u003e \u003cp\u003e87.53%\u003c/p\u003e \u003cp\u003e86.21%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD) (n\u0026thinsp;=\u0026thinsp;3)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe gel formulation with nanocarriers is a superior choice for treating rheumatoid arthritis due to its superior skin penetration compared to other topical semi-solid formulations. Nanocarriers facilitate the diffusion of pharmaceuticals more profoundly into the epidermal layers, thereby enhancing their pharmacological efficacy. The solvent emulsion diffusion process was employed to effectively develop celecoxib nanosponges (CENS1-CENS9), which reached nanoscale particle sizes as a result of the ethyl cellulose (EC) and polyvinyl alcohol (PVA) ratios. The 32 full factorial design was employed to achieve this. The polymer ratios employed have an impact on the physicochemical characteristics of nine Nanosponges that have been investigated for therapeutic purposes. Spherical nanosponges contain the medication. The stability, anti-inflammatory efficacy, and drug diffusion of all gel formulations were assessed using Franz diffusion cells. The results demonstrated significant anti-inflammatory efficacy, favorable release patterns, and excellent drug loading efficiency. The results indicate that the gel laden with celecoxib is effective, suggesting that it could be employed as a carrier for improved rheumatoid arthritis treatment.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enanosponge\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEthyl Cellulose\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePVA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePolyvinyl alcohol\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDOE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eExperimental Design\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEntrapment Efficiency\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDCM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ediffusion of dichloromethane\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eXRD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eX-ray diffraction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSEM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eScanning electron microscopy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTEM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTransmission electron microscopy.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eI hereby declare that this submission is entirely my own work, in my own words, and that all sources used in researching it are fully acknowledged and all quotations properly identified.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatement of Informed Consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere are no human subjects in this article and informed consent is not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the authors have read and agreed to the final copy of the finding as contained in the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets/information used for this study is available on reasonable request to the corresponding author.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicting interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors report that there was no conflict of interest in this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author(s) received for funding this work through Large Research Project under grant number RGP2/530/45.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical Approval is not applicable for this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSTS and SPNB\u0026nbsp;initiated the conception.\u0026nbsp;STS, SPNB and PN\u0026nbsp;developed the design.\u0026nbsp;STS, SPNB, PN, BRN and MAAA\u0026nbsp;conducted the experiments. STS, SPNB and BRN analyzed the results.\u0026nbsp;STS, SPNB, BRN and MAAA prepared the first draft of the manuscript. STS, SPNB, PN, BRN and MAAA reviewed and edited the manuscript. The authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors extend their appreciation to the Deanship of Research and Graduate Studies at King Khalid University for funding this work through Large Research Project under grant number RGP2/530/45.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eList of Abbreviations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNS: nanosponge, EA: Ethyl Cellulose, PVA: Polyvinyl alcohol, DOE: Experimental Design, EE: Entrapment Efficiency, DCM: diffusion of dichloromethane, XRD: X-ray diffraction, SEM: Scanning electron microscopy, TEM: Transmission electron microscopy.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSim, S. \u0026amp; Wong, N. Nanotechnology and its use in imaging and drug delivery (Review). \u003cem\u003eBiomed. 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Evaluation of antioxidant and anti-inflammatory activity of methanol extract of Oxalis corniculata. \u003cem\u003ePlanta Med.\u003c/em\u003e \u003cb\u003e75\u003c/b\u003e, s\u0026ndash;0029 (2009).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Celecoxib, Nanosponges, 3 2 full factorial design, Optimization, Anti-Inflammatory activity","lastPublishedDoi":"10.21203/rs.3.rs-6009743/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6009743/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOsteoarthritis is characterised by degenerative changes, while rheumatoid arthritis is an inflammatory disorder characterised by swelling and inflammation in the synovial membranes of the joints, which leads to bone erosion and joint deformity. Although new drugs have expanded treatment options, severe rheumatoid arthritis can significantly impair physical functions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUsing Emulsion Solvent Evaporation technology with a 3\u003csup\u003e2\u003c/sup\u003e-factorial design. Various concentrations of ethyl-cellulose (EC) and poly-vinyl alcohol (PVA) as rate-inhibiting copolymers. The Nanosponges were also tested for particle size (PS), zeta potential (ZP), entrapment efficacy (EE), and drug loading. It was subjected to physicochemical characterisation using FT-IR, XRD, TEM and SEM. The Carbopol 934P gel was treated with an optimised CENS containing an equal amount of Celecoxib. The celecoxib-loaded NS gel was further tested for viscosity, spreadability, drug diffusion, stability, and skin irritation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCENS2 was constituted of Celecoxib, EC, and PVA, with particle size (259 ± 0.63nm), ZP (-7.01 ± 0.01 mV), and %EE (98.1%). The physicochemical tests of the produced NS showed polymer-drug compatibility, efficient drug encapsulation, and that the drug remained non-crystalline within the spherical NS. CENS3 topical gels revealed 86.3% drug diffusion in Franz cells after good drug release.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe current study suggests that a The CENS3-based gel could improve the transdermal delivery process without inducing skin irritation. Celecoxib Nanosponges gel could prove effective against Rheumatoid arthritis.\u003c/p\u003e","manuscriptTitle":"Development and in-vitro Assessment of Topical Gel of Celecoxib-Loaded Nanosponges for the Rheumatoid Arthritis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-17 13:40:12","doi":"10.21203/rs.3.rs-6009743/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"01b06744-1218-469e-a2b3-6f7427c8cb0b","owner":[],"postedDate":"February 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":44334265,"name":"Biological sciences/Drug discovery"},{"id":44334266,"name":"Health sciences/Rheumatology"}],"tags":[],"updatedAt":"2025-02-26T07:23:52+00:00","versionOfRecord":[],"versionCreatedAt":"2025-02-17 13:40:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6009743","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6009743","identity":"rs-6009743","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}