Quality-by-Design Optimization of Electrospinning Parameters to Formulate Scaffolds for Topical Inflammatory Disease Management via Drug Repurposing


  • Alka Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya Vihar, Raebareli Road, Lucknow-226025, Uttar Pradesh, India
  • Shubhini A. Saraf Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya Vihar, Raebareli Road, Lucknow-226025, Uttar Pradesh, India




Electrospinning, CS/PVA polyblend nanofiber scaffolds, experimental design, surface morphology


This study investigates the fabrication of chitosan (CS)/polyvinyl alcohol (PVA) blend nanofibers via electrospinning, aiming to create nanofibers with enhanced properties for broad applications. The research focuses on optimizing electrospinning parameters to reduce bead formation and achieve uniform nanofiber morphology. A detailed experimental design, employing a nineteen-point plan developed with Design-Expert software, examined variables such as polymer concentration, distance from the needle to the collector, the required voltage, and the rate at which solution was ejected from the needle. Morphological characteristics of the nanofibers were analyzed using advanced microscopy, complemented by drug release and wound healing assessments. The optimal electrospinning conditions were determined to be a 1:3 CS/PVA solution concentration ratio, an 8 cm needle-to-collector distance, a 20 kV applied voltage, and a 1 mL/hour flow rate. Scanning electron microscopy revealed uniform nanofibers with diameters between 100 to 250 nm, devoid of bead defects. In-vitro analysis demonstrated a sustained release profile of azilsartan (AZL), while in-vivo studies on rats indicated enhanced wound healing, corroborated by histological examination. The findings suggest that CS/PVA nanofibers, fabricated under these conditions, possess promising characteristics for use as a drug-delivery scaffold in wound treatment applications.


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Arora D, Nanda S. Quality by design driven development of resveratrol loaded ethosomal hydrogel for improved dermatological benefits via enhanced skin permeation and retention. International journal of pharmaceutics. 2019;567:1-13. Available from: doi.org/10.1016/j.ijpharm.2019.118448

Tomar Y, Pandit N, Priya S, Singhvi G. Evolving Trends in Nanofibers for Topical Delivery of Therapeutics in Skin Disorders. ACS Omega. 2023;8(21):18340-18357. Available from: doi.org/10.1021/acsomega.3c00924

Alka, Verma A, Mishra N, Singh N, Singh P, Nisha R, et al. Polymeric Gel Scaffolds and Biomimetic Environments for Wound Healing. Current pharmaceutical design. 2023;29(40):3221-3239. Available from: doi.org/10.2174/1381612829666230816100631

Wadke P, Chhabra R, Jain R, Dandekar P. Silver-embedded starch-based nanofibrous mats for soft tissue engineering. Surfaces Interfaces. 2017;8:137-146. Available from: doi.org/10.1016/j.surfin.2017.05.008

Samadian H, Zamiri S, Ehterami A, Farzamfar S, Vaez A, Khastar H, et al. Electrospun cellulose acetate/gelatin nanofibrous wound dressing containing berberine for diabetic foot ulcer healing: in vitro and in vivo studies. Scientific Reports. 2020;10(1):1-12. Available from: doi.org/10.1038/s41598-020-65268-7

Xue J, He M, Liang Y, Crawford A, Coates P, Chen D, et al. Fabrication and evaluation of electrospun PCL–gelatin micro-/nanofiber membranes for anti-infective GTR implants. Journal of Materials Chemistry B. 2014;2(39):6867-6877. Available from: doi.org/10.1039/C4TB00737A

Cui Z, Zheng Z, Lin L, Si J, Wang Q, Peng X, et al. Electrospinning and crosslinking of polyvinyl alcohol/chitosan composite nanofiber for transdermal drug delivery. Advances in Polymer Technology. 2018;37(6):1917-1928. Available from: doi.org/10.1002/adv.21850

Dwivedi C, Pandey I, Pandey H, Patil S, Mishra SB, Pandey AC, et al. In vivo diabetic wound healing with nanofibrous scaffolds modified with gentamicin and recombinant human epidermal growth factor. Journal of Biomedical Materials Research Part A. 2018;106(3):641-651. Available from: doi.org/10.1002/jbm.a.36268

Rathinavel S, Indrakumar J, Korrapati PS, Dharmalingam S. Synthesis and fabrication of amine functionalized SBA-15 incorporated PVA/Curcumin nanofiber for skin wound healing application. Colloids Surfaces A: Physicochemical Engineering Aspects. 2022;637:1-10. Available from: doi.org/10.1016/j.colsurfa.2021.128185

Ajmal G, Bonde GV, Mittal P, Khan G, Pandey VK, Bakade BV, et al. Biomimetic PCL-gelatin based nanofibers loaded with ciprofloxacin hydrochloride and quercetin: A potential antibacterial and anti-oxidant dressing material for accelerated healing of a full thickness wound. International journal of pharmaceutics. 2019;567:1-12. Available from: doi.org/10.1016/j.ijpharm.2019.118480

Gu Z, Xie H, Huang C, Li L, Yu X. Preparation of chitosan/silk fibroin blending membrane fixed with alginate dialdehyde for wound dressing. International journal of biological macromolecules. 2013;58:121-126. Available from: doi.org/10.1016/j.ijbiomac.2013.03.059

Levengood SKL, Zhang M. Chitosan-based scaffolds for bone tissue engineering. Journal of Materials Chemistry B. 2014;2(21):3161-3184. Available from: doi.org/10.1039/C4TB00027G

Karthick SA, Manjari K, Devi MG. Biocompatible and bioactive PVA/Sericin/Chitosan nanofibrous wound dressing matrix. Applied Surface Science Advances. 2023;13:1-8. Available from: doi.org/10.1016/j.apsadv.2022.100362

Xu Z, Shi L, Yang M, Zhang H, Zhu L. Fabrication of a novel blended membrane with chitosan and silk microfibers for wound healing: characterization, in vitro and in vivo studies. Journal of Materials Chemistry B. 2015;3(17):3634-3642. Available from: doi.org/10.1039/C5TB00226E

Fathollahipour S, Abouei Mehrizi A, Ghaee A, Koosha M. Electrospinning of PVA/chitosan nanocomposite nanofibers containing gelatin nanoparticles as a dual drug delivery system. Journal of Biomedical Materials Research Part A. 2015;103(12):3852-3862. Available from: doi.org/10.1002/jbm.a.35529

Pradhan A, Tiwari A, Sethi R. Azilsartan: Current Evidence and Perspectives in Management of Hypertension. International journal of hypertension. 2019;2019:1-8. Available from: doi.org/10.1155/2019/1824621

Jones JD, Jackson SH, Agboton C, Martin TS. Azilsartan Medoxomil (Edarbi): The Eighth Angiotensin II Receptor Blocker. Pharmacy and Therapeutics 2011;36(10):634-640.

Akershoek JJ, Brouwer KM, Vlig M, Boekema BK, Beelen RH, Middelkoop E, et al. Differential effects of Losartan and Atorvastatin in partial and full thickness burn wounds. PloS one. 2017;12(6):1-20. Available from: doi.org/10.1371/journal.pone.0179350

Charernsriwilaiwat N, Rojanarata T, Ngawhirunpat T, Opanasopit P. Electrospun chitosan/polyvinyl alcohol nanofibre mats for wound healing. International wound journal. 2014;11(2):215-222. Available from: doi.org/10.1111/j.1742-481X.2012.01077.x

Koosha M, Mirzadeh H. Electrospinning, mechanical properties, and cell behavior study of chitosan/PVA nanofibers. Journal of Biomedical Materials Research Part A. 2015;103(9):3081-3093. Available from: doi.org/10.1002/jbm.a.35443

Wang T, Chen Y, Dong W, Liu Y, Shi L, Chen R, et al. Fractal Characteristics of Porosity of Electrospun Nanofiber Membranes. Mathematical Problems in Engineering. 2020;2020:1-8. Available from: doi.org/10.1155/2020/2503154

Yew CHT, Azari P, Choi JR, Muhamad F, Pingguan-Murphy B. Electrospun Polycaprolactone Nanofibers as a Reaction Membrane for Lateral Flow Assay. Polymers. 2018;10(12):1-14. Available from: doi.org/10.3390/polym10121387

Adeli B, Gharehaghaji AA, Jeddi AAA. A feasibility study on production and optimization of PVDF/PU polyblend nanofiber layers using expert design analysis. Iranian Polymer Journal. 2021;30(6):535-545. Available from: doi.org/10.1007/s13726-021-00910-3

Miele D, Catenacci L, Rossi S, Sandri G, Sorrenti M, Terzi A, et al. Collagen/PCL Nanofibers Electrospun in Green Solvent by DOE Assisted Process. An Insight into Collagen Contribution. Materials (Basel, Switzerland). 2020;13(21):1-24. Available from: doi.org/10.1007/s13726-021-00910-3

Jadbabaei S, Kolahdoozan M, Naeimi F, Ebadi-Dehaghani H. Preparation and characterization of sodium alginate–PVA polymeric scaffolds by electrospinning method for skin tissue engineering applications. RSC Advances. 2021;11(49):30674-30688. Available from: doi.org/10.1039/D1RA04176B

Sharma D, Patel N, Panjabi S, Patel V. Structural, morphological, optical, and thermal properties of electrospun PbS/PVP-PEO nanofibers. Ceramics International. 2023;49(6):8839-8846. Available from: doi.org/10.1016/j.ceramint.2022.11.038

Mohd F, Bontha L, Bontha V, Vemula S. Formulation and evaluation of transdermal films of ondansetron hydrochloride. MOJ Bioequivalence & Bioavailability. 2017;3(4):86-92. Available from: doi.org/10.15406/mojbb.2017.03.00039

Maftoonazad N, Ramaswamy H. Design and testing of an electrospun nanofiber mat as a pH biosensor and monitor the pH associated quality in fresh date fruit (Rutab). Polymer Testing. 2019;75:76-84. Available from: doi.org/10.1016/j.polymertesting.2019.01.011

Sayin S, Tufani A, Emanet M, Genchi GG, Sen O, Shemshad S, et al. Electrospun Nanofibers With pH-Responsive Coatings for Control of Release Kinetics. Frontiers in bioengineering and biotechnology. 2019;7:1-12. Available from: doi.org/10.3389/fbioe.2019.00309

Junmahasathien T, Panraksa P, Protiarn P, Hormdee D, Noisombut R, Kantrong N, et al. Preparation and evaluation of metronidazole-loaded pectin films for potentially targeting a microbial infection associated with periodontal disease. Polymers. 2018;10(9):1-12. Available from: doi.org/10.3390/polym10091021

Langwald SV, Ehrmann A, Sabantina L. Measuring physical properties of electrospun nanofiber mats for different biomedical applications. Membranes. 2023;13(5):1-23. Available from: doi.org/10.3390/membranes13050488

Begum MY, Alqahtani A, Ghazwani M, Ramakrishna MM, Hani U, Atiya A, et al. Preparation of Carbopol 934 Based Ketorolac Tromethamine Buccal Mucoadhesive Film: In Vitro, Ex Vivo, and In Vivo Assessments. International Journal of Polymer Science. 2021;2021:1-11. Available from: doi.org/10.1155/2021/4786488

Nandi S, Mondal S. Fabrication and evaluation of matrix type novel transdermal patch loaded with tramadol hydrochloride. Turkish Journal of Pharmaceutical Sciences. 2022;19(5):572-582. Available from: doi.org/10.4274/tjps.galenos.2021.43678

Bhatt DC, Dhake AS, Khar RK, Mishra DN. Development and in vitro evaluation of transdermal matrix films of metoprolol tartrate. Yakugaku Zasshi. 2008;128(9):1325-1331. Available from: doi.org/10.1248/yakushi.128.1325

Abid S, Hussain T, Nazir A, Zahir A, Khenoussi N. A novel double-layered polymeric nanofiber-based dressing with controlled drug delivery for pain management in burn wounds. Polymer Bulletin. 2019;76(12):6387-6411. Available from: doi.org/10.1007/s00289-019-02727-w

Kumar V, Khan AA, Nagarajan K. Animal models for the evaluation of wound healing activity. Int Bull Drug Res. 2013;3(5):93-107.

Nikfarjam S, Aldubaisi Y, Swami V, Swami V, Xu G, Vaughan MB, et al. Polycaprolactone Electrospun Nanofiber Membrane with Skin Graft Containing Collagen and Bandage Containing MgO Nanoparticles for Wound Healing Applications. Polymers. 2023;15(9):1-17. Available from: doi.org/10.3390/polym15092014

Samadian H, Salehi M, Farzamfar S, Vaez A, Ehterami A, Sahrapeyma H, et al. In vitro and in vivo evaluation of electrospun cellulose acetate/gelatin/hydroxyapatite nanocomposite mats for wound dressing applications. Artificial cells, nanomedicine, biotechnology. 2018;46(sup1):964-974. Available from: doi.org/10.1080/21691401.2018.1439842

de Aquino PEA, de Souza TdFG, Santos FA, Viana AFSC, Louchard BO, Leal LKAM, et al. The Wound Healing Property of N-Methyl-(2 S, 4 R)-trans-4-Hydroxy-L-Proline from Sideroxylon obtusifolium is Related to its Anti-Inflammatory and Antioxidant Actions. Journal of evidence-based integrative medicine. 2019;24:1-11. Available from: doi.org/10.1177/2515690X19865166

El Massoudi S, Zinedine A, Rocha JM, Benidir M, Najjari I, El Ghadraoui L, et al. Phenolic composition and wound healing potential assessment of Moroccan henna (Lawsonia inermis) aqueous extracts. Cosmetics. 2023;10(3):1-13. Available from: doi.org/10.3390/cosmetics10030092

Ghelich R, Jahannama MR, Abdizadeh H, Torknik FS, Vaezi MR. Central composite design (CCD)-Response surface methodology (RSM) of effective electrospinning parameters on PVP-B-Hf hybrid nanofibrous composites for synthesis of HfB2-based composite nanofibers. Composites Part B: Engineering. 2019;166:527-541. Available from: doi.org/10.1016/j.compositesb.2019.01.094

Sasikala L, Rathinamoorthy R, Dhurai B. Optimization of process conditions for chitosan-manuka honey film as wound contact layer for wound dressings. Wound Medicine. 2018;23:11-21. Available from: doi.org/10.1016/j.wndm.2018.09.007

Ahmadipourroudposht M, Fallahiarezoudar E, Yusof NM, Idris A. Application of response surface methodology in optimization of electrospinning process to fabricate (ferrofluid/polyvinyl alcohol) magnetic nanofibers. Materials science & engineering C, Materials for biological applications. 2015;50:234-241. Available from: doi.org/10.1016/j.msec.2015.02.008

Akrami-Hasan-Kohal M, Tayebi L, Ghorbani M. Curcumin-loaded naturally-based nanofibers as active wound dressing mats: morphology, drug release, cell proliferation, and cell adhesion studies. New Journal of Chemistry. 2020;44(25):10343-10351. Available from: doi.org/10.1039/D0NJ01594F

Zielinska A, Karczewski J, Eder P, Kolanowski T, Szalata M, Wielgus K, et al. Scaffolds for drug delivery and tissue engineering: The role of genetics. Journal of Controlled Release. 2023;359:207-223. Available from: doi.org/10.1016/j.jconrel.2023.05.042

Bonferoni MC, Caramella C, Catenacci L, Conti B, Dorati R, Ferrari F, et al. Biomaterials for Soft Tissue Repair and Regeneration: A Focus on Italian Research in the Field. Pharmaceutics. 2021;13(9):1-39. Available from: doi.org/10.3390/pharmaceutics13091341

Zhang X, Wang Y, Gao Z, Mao X, Cheng J, Huang L, et al. Advances in wound dressing based on electrospinning nanofibers. Journal of Applied Polymer Science. 2024;141(1):1-28. Available from: doi.org/10.1002/app.54746

Bhattarai N, Edmondson D, Veiseh O, Matsen FA, Zhang MJB. Electrospun chitosan-based nanofibers and their cellular compatibility. Biomaterials. 2005;26(31):6176-6184. Available from: doi.org/10.1016/j.biomaterials.2005.03.027

Mata GCd, Morais MS, Oliveira WPd, Aguiar ML. Composition effects on the morphology of PVA/chitosan electrospun nanofibers. Polymers. 2022;14(22):1-19. Available from: doi.org/10.3390/polym14224856

Homayoni H, Ravandi SAH, Valizadeh M. Electrospinning of chitosan nanofibers: Processing optimization. Carbohydrate polymers. 2009;77(3):656-661. Available from: doi.org/10.1016/j.carbpol.2009.02.008

Anstey A, Chang E, Kim ES, Rizvi A, Kakroodi AR, Park CB, et al. Nanofibrillated polymer systems: Design, application, and current state of the art. Progress in Polymer Science. 2021;113:1-119. Available from: doi.org/10.1016/j.progpolymsci.2020.101346

Thien DVH. Electrospun chitosan/PVA nanofibers for drug delivery. Vietnam Journal of Science Technology. 2016;54(4B):185-192. Available from: doi.org/ 10.15625/2525-2518/54/4B/12040

Jones EM, Cochrane CA, Percival SL. The effect of pH on the extracellular matrix and biofilms. Advances in wound care. 2015;4(7):431-439. Available from: doi.org/10.1089/wound.2014.0538

Kajdic S, Planinsek O, Gasperlin M, Kocbek P. Electrospun nanofibers for customized drug-delivery systems. Journal of Drug Delivery Science Technology. 2019;51:672-681. Available from: doi.org/10.1016/j.jddst.2019.03.038

Yang Y, Xia T, Zhi W, Wei L, Weng J, Zhang C, et al. Promotion of skin regeneration in diabetic rats by electrospun core-sheath fibers loaded with basic fibroblast growth factor. Biomaterials. 2011;32(18):4243-4254. Available from: doi.org/10.1016/j.biomaterials.2011.02.042

Martin P. Wound healing--aiming for perfect skin regeneration. Science. 1997;276(5309):75-81. Available from: doi.org/10.1126/science.276.5309.75






Research Article

How to Cite

“Quality-by-Design Optimization of Electrospinning Parameters to Formulate Scaffolds for Topical Inflammatory Disease Management via Drug Repurposing”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 16, no. 2, Mar. 2024, pp. 237-50, https://doi.org/10.25004/IJPSDR.2024.160214.