Development of Mucoadhesive Nanofiber Platform Using Eudragit® E100 for Vaginal Application

Year 2025, Volume: 45 Issue: 3, 245 - 254, 01.09.2025

Sinem Saar , Fatma Nur Tuğcu Demiröz , Fusun Acarturk

https://doi.org/10.52794/hujpharm.1764755

Abstract

Electrospun nanofibers represent an excellent alternative to classical vaginal dosage forms due to flexibility, high loading capacity, high mucoadhesive strength and enhanced patient compliance. Eudragit®s, which are synthetic polymers composed of methacrylate monomers, are preferred for vaginal drug delivery. The aim of this study was to develop and evaluate Eudragit®-based nanofiber formulations for vaginal drug delivery. Nanofibers were fabricated using electrospinning. Eudragit® E100 at varying polymer concentrations dissolved in an ethanol:dimethylformamide mixture (7:3, v/v). The polymer solutions were characterized in terms of surface tension, viscosity, and electrical conductivity. Thermal behavior of both the raw polymer and the nanofiber formulations was analyzed using Differential Scanning Calorimetry. Surface wettability was assessed by contact angle measurements using an optical tensiometer. The mechanical strength and mucoadhesive properties of the nanofibers were evaluated using a texture analyzer. The viscosity, surface tension and conductivity of the polymer solutions were found to be suitable for electrospinning. All formulations had hydrophobic properties. Mechanical properties of formulations were increased with increasing polymer concentration. Formulation E4 exhibited the highest mucoadhesion value among all tested formulations, clearly demonstrating to adhere to the mucosal surface. It was seen that Eudragit-based formulations may be a potential platform for vaginal application.

Keywords

Electrospinning , Nanofiber , Vaginal drug delivery , Eudragit

Ethical Statement

Ethics Committee Approval is not required for this study.

Supporting Institution

Gazi University Scientific Research Projects Coordination Unit

Project Number

02/2020-17

Thanks

This study was supported by Gazi University Scientific Research Projects Coordination Unit under grant number 02/2020-17. The authors would like to thank Evonik Industries for kindly providing Eudragit® E100 for research purposes.

References

• 1. Subi MTM, Nandhakumar S, Vasanthi HR. Vaginal drug delivery system: A promising route of drug administration for local and systemic diseases. Drug Discov. Today. 2024:104012. https://doi.org/10.1517/17425247.2011.600119
• 2. Yu T, Malcolm K, Woolfson D, Jones DS, Andrews GP. Vaginal gel drug delivery systems: understanding rheological characteristics and performance. Expert Opin. Drug Deliv. 2011;8(10):1309-22. https://doi.org/10.1517/17425247.2011.600119
• 3. Ensign LM, Cone R, Hanes J. Nanoparticle-based drug delivery to the vagina: a review. J. Control. Release. 2014;190:500-14. https://doi.org/10.1016/j.jconrel.2014.04.033
• 4. Cazorla-Luna R, Ruiz-Caro R, Veiga M-D, Malcolm RK, Lamprou DA. Recent advances in electrospun nanofiber vaginal formulations for women's sexual and reproductive health. Int. J. Pharm. 2021;607:121040. https://doi.org/10.1016/j.ijpharm.2021.121040
• 5. Tuğcu-Demiröz F, Saar S, Kara AA, Yıldız A, Tunçel E, Acartürk F. Development and characterization of chitosan nanoparticles loaded nanofiber hybrid system for vaginal controlled release of benzydamine. Eur. J. Pharm. Sci. 2021;161:105801. https://doi.org/10.1016/j.ejps.2021.105801
• 6. Tort S, Han D, Frantz E, Steckl AJ. Controlled drug release of parylene-coated pramipexole nanofibers for transdermal applications. Surf. Coat. Technol. 2021;409:126831. https://doi.org/10.1016/j.surfcoat.2021.126831
• 7. Blakney AK, Ball C, Krogstad EA, Woodrow KA. Electrospun fibers for vaginal anti-HIV drug delivery. Antiviral Res. 2013;100:S9-S16. https://doi.org/10.1016/j.antiviral.2013.09.022
• 8. Minooei F, Gilbert NM, Zhang L, Sarah Necamp M, Mahmoud MY, Kyser AJ, et al. Rapid-dissolving electrospun nanofibers for intra-vaginal antibiotic or probiotic delivery. Eur. J. Pharm. Biopharm. 2023;190:81-93. https://doi.org/10.1016/j.ejpb.2023.07.009
• 9. Vidyadhari A, Singh AK, Ralli T, Parvez S, Kohli K. Drug-loaded electrospun nanofiber for Vulvovaginal candidiasis: A systematic literature review. Clin. Epidemiol. Glob. Health. 2023;24:101420. https://doi.org/10.1016/j.cegh.2023.101420
• 10. Pradhan M, Basha NS, Sahu KK, Yadav K, Dubey A, Pradhan HK, Kirubakaran J. Engineering Nanofibers for Cutaneous Drug Delivery Systems and Therapeutic Applications. Med. Nov. Technol. Devices. 2025:100386. https://doi.org/10.1016/j.medntd.2025.100386
• 11. Yıldız A, Kara AA, Acartürk F. Peptide-protein based nanofibers in pharmaceutical and biomedical applications. Int. J. Biol. Macromol. 2020;148:1084-97. https://doi.org/10.1016/j.ijbiomac.2019.12.275
• 12. Tuğcu-Demiröz F, Saar S, Tort S, Acartürk F. Electrospun metronidazole-loaded nanofibers for vaginal drug delivery. Drug Dev. Ind. Pharm. 2020;46(6):1015-25. https://doi.org/10.1080/03639045.2020.1767125
• 13. Wang C, Wang W, Qi H, Dai Y, Jiang S, Ding B, et al. Electrospinning and electrospun nanofibers: From academic research to industrial production. Prog. Mater. Sci. 2025:101494. https://doi.org/10.1016/j.pmatsci.2025.101494
• 14. Saar S, Demiröz FNT. Evaluation of Mechanical and Mucoadhesive Properties of Polyvinyl Alcohol Nanofibers As Vaginal Drug Delivery System. FABAD J. Pharm. Sci. 2023;48(2):219-30. https://doi.org/10.55262/fabadeczacilik.1268029
• 15. Xing J, Zhang M, Liu X, Wang C, Xu N, Xing D. Multi-material electrospinning: from methods to biomedical applications. Mater. Today Bio. 2023;21:100710. https://doi.org/10.1016/j.mtbio.2023.100710
• 16. Turanlı Y, Tort S, Acartürk F. Development and characterization of methylprednisolone loaded delayed release nanofibers. J. Drug Deliv. Sci. Technol. 2019;49:58-65. https://doi.org/10.1016/j.jddst.2018.10.031
• 17. Chen H, Su J, Brennan CS, Van Der Meeren P, Zhang N, Tong Y, Wang P. Recent developments of electrospun zein nanofibres: Strategies, fabrication and therapeutic applications. Mater. Today Adv. 2022;16:100307. https://doi.org/10.1016/j.mtadv.2022.100307
• 18. Ataei M, Afrasiabi Garekani H, Alizadeh Sani M, Julian Mcclements D, Sadeghi F. Evaluation of polyvinyl pyrrolidone nanofibers for encapsulation, protection, and release of curcumin: Impact on in vitro bioavailability. J. Mol. Liq. 2024;397:124115. https://doi.org/10.1016/j.molliq.2024.124115
• 19. Krogstad EA, Ramanathan R, Nhan C, Kraft JC, Blakney AK, Cao S, et al. Nanoparticle-releasing nanofiber composites for enhanced in vivo vaginal retention. Biomaterials. 2017;144:1-16. https://doi.org/10.1016/j.biomaterials.2017.07.034
• 20. Singhal P. Preparation and characterization of poly (E-CAPROLACTONE) nano fibers by electrospinning technique for tissue enginerring applications. Mater. Today Proc. 2021;37:2997-3001. https://doi.org/10.1016/j.matpr.2020.08.716
• 21. Aranaz I, Alcántara AR, Civera MC, Arias C, Elorza B, Heras Caballero A, Acosta N. Chitosan: An Overview of Its Properties and Applications. Polymers. 2021;13(19):3256. https://doi.org/10.3390/polym13193256
• 22. Satchanska G, Davidova S, Petrov PD. Natural and Synthetic Polymers for Biomedical and Environmental Applications. Polymers. 2024;16(8):1159. https://doi.org/10.3390/polym16081159
• 23. Gonciarz W, Balcerczak E, Brzeziński M, Jeleń A, Pietrzyk-Brzezińska AJ, Narayanan VHB, Chmiela M. Chitosan-based formulations for therapeutic applications. A recent overview. J. Biomed. Sci. 2025;32(1). https://doi.org/10.1186/s12929-025-01161-7
• 24. Bolívar-Monsalve EJ, Alvarez MM, Hosseini S, Espinosa-Hernandez MA, Ceballos-González CF, Sanchez-Dominguez M, et al. Engineering bioactive synthetic polymers for biomedical applications: a review with emphasis on tissue engineering and controlled release. Mater. Adv. 2021;2(14):4447-78. https://doi.org/10.1039/d1ma00092f
• 25. Xue J, Wu T, Dai Y, Xia Y. Electrospinning and Electrospun Nanofibers: Methods, Materials, and Applications. Chem. Rev. 2019;119(8):5298-415. https://doi.org/10.1021/acs.chemrev.8b00593
• 26. Reddy MSB, Ponnamma D, Choudhary R, Sadasivuni KK. A Comparative Review of Natural and Synthetic Biopolymer Composite Scaffolds. Polymers. 2021;13(7):1105. https://doi.org/10.3390/polym13071105
• 27. Nikam A, Sahoo PR, Musale S, Pagar RR, Paiva-Santos AC, Giram PS. A Systematic Overview of Eudragit® Based Copolymer for Smart Healthcare. Pharmaceutics. 2023;15(2):587. https://doi.org/10.3390/pharmaceutics15020587
• 28. Yoo J-W, Giri N, Lee CH. pH-sensitive Eudragit nanoparticles for mucosal drug delivery. Int. J. Pharm. 2011;403(1-2):262-7. https://doi.org/10.1016/j.ijpharm.2010.10.032
• 29. Patra CN, Priya R, Swain S, Kumar Jena G, Panigrahi KC, Ghose D. Pharmaceutical significance of Eudragit: A review. Future J. Pharm. Sci. 2017;3(1):33-45. https://doi.org/10.1016/j.fjps.2017.02.001
• 30. Alasino RV, Leonhard V, Bianco ID, Beltramo DM. Eudragit E100 surface activity and lipid interactions. Colloids Surf. B Biointerfaces. 2012;91:84-9. https://doi.org/10.1016/j.colsurfb.2011.10.041
• 31. Baranauskaite J, Adomavičiūtė E, Jankauskaitė V, Marksa M, Barsteigienė Z, Bernatoniene J. Formation and investigation of electrospun Eudragit E100/oregano mats. Molecules. 2019;24(3):628. https://doi.org/10.3390/molecules24030628
• 32. Turanlı Y, Acartürk F. Fabrication and characterization of budesonide loaded colon-specific nanofiber drug delivery systems using anionic and cationic polymethacrylate polymers. J. Drug Deliv. Sci. Technol. 2021;63:102511. https://doi.org/10.1016/j.jddst.2021.102511
• 33. Małolepsza-Jarmołowska K, Kubis A. Studies on gynaecological hydrophilic lactic acid preparations. Part 3: Effects of chitosan on the properties of methylcellulose gels. Die Pharmazie. 2000;55(8):610-1.
• 34. Vedha Hari B, Narayanan N, Dhevedaran K. Efavirenz–eudragit E-100 nanoparticle-loaded aerosol foam for sustained release: In-vitro and ex-vivo evaluation. Chem. Pap. 2015;69(2):358-67. https://doi.org/10.1515/chempap-2015-0005
• 35. Chinnappan BA, Krishnaswamy M, Xu H, Hoque ME. Electrospinning of biomedical nanofibers/nanomembranes: Effects of process parameters. Polymers. 2022;14(18):3719. https://doi.org/10.3390/polym14183719
• 36. Turanlı Y, Birer M, Birer YT, Uyar R, Dikmen BY, Acartürk F. Oral fast-dissolving risperidone loaded electrospun nanofiber drug delivery systems for antipsychotic therapy. J. Drug Deliv. Sci. Technol. 2024;92:105262. https://doi.org/10.1016/j.jddst.2023.105262
• 37. Rüzgar G, Birer M, Tort S, Acartürk F. Studies on improvement of water-solubility of curcumin with electrospun nanofibers. FABAD J. Pharm. Sci. 2013;38(3):143.
• 38. Gajewski A. A couple new ways of surface tension determination. Int. J. Heat Mass Transf. 2017;115:909-17. https://doi.org/10.1016/j.ijheatmasstransfer.2017.08.050
• 39. Birer M, Kara AA, Yurdakok-Dikmen B, Uyar R, Aralan G, Birer YT, et al. Electrospun hesperidin nanofibers induce a cytoprotective effect on sodium-fluoride induced oxidative stress in vitro. J. Drug Deliv. Sci. Technol. 2024;92:105388. https://doi.org/10.1016/j.jddst.2024.105388
• 40. Birer M, Acartürk F. Telmisartan loaded polycaprolactone/gelatin-based electrospun vascular scaffolds. Int. J. Polym. Mater. Polym. Biomater. 2022;71(11):858-73. https://doi.org/10.1080/00914037.2021.1915785
• 41. Tort S, Yıldız A, Tuğcu-Demiröz F, Akca G, Kuzukıran Ö, Acartürk F. Development and characterization of rapid dissolving ornidazole loaded PVP electrospun fibers. Pharm. Dev. Technol. 2019;24(7):864-73. https://doi.org/10.1080/10837450.2019.1615088
• 42. Tort S, Acartürk F. Preparation and characterization of electrospun nanofibers containing glutamine. Carbohydr. Polym. 2016;152:802-14. https://doi.org/10.1016/j.carbpol.2016.07.028
• 43. Tuğcu-Demiröz F, Acartürk F, Erdoğan D. Development of long-acting bioadhesive vaginal gels of oxybutynin: Formulation, in vitro and in vivo evaluations. Int. J. Pharm. 2013;457(1):25-39. https://doi.org/10.1016/j.ijpharm.2013.09.003
• 44. Rüzgar Özemre G, Kara AA, Pezik E, Tort S, Vural İ, Acartürk F. Preparation of nanodelivery systems for oral administration of low molecular weight heparin. J. Drug Deliv. Sci. Technol. 2023;79:104068. https://doi.org/10.1016/j.jddst.2022.104068
• 45. Al-Abduljabbar A, Farooq I. Electrospun polymer nanofibers: processing, properties, and applications. Polymers. 2022;15(1):65. https://doi.org/10.3390/polym15010065
• 46. Sánchez-Cid P, Rubio-Valle JF, Jiménez-Rosado M, Pérez-Puyana V, Romero A. Effect of solution properties in the development of cellulose derivative nanostructures processed via electrospinning. Polymers. 2022;14(4):665. https://doi.org/10.3390/polym14040665
• 47. Pillay V, Dott C, Choonara YE, Tyagi C, Tomar L, Kumar P, et al. A review of the effect of processing variables on the fabrication of electrospun nanofibers for drug delivery applications. J. Nanomater. 2013;2013(1):789289. https://doi.org/10.1155/2013/789289
• 48. Linares V, Yarce CJ, Echeverri JD, Galeano E, Salamanca CH. Relationship between degree of polymeric ionisation and hydrolytic degradation of Eudragit® E polymers under extreme acid conditions. Polymers. 2019;11(6):1010. https://doi.org/10.3390/polym11061010
• 49. Riaz U, Ashraf SM. Characterization of Polymer Blends with FTIR Spectroscopy. Wiley-VCH Verlag GmbH & Co. KGaA; 2014. p. 625-78. https://doi.org/10.1002/9783527645602.ch20
• 50. Vlachou M, Kikionis S, Siamidi A, Kyriakou S, Tsotinis A, Ioannou E, Roussis V. Development and characterization of Eudragit®-based electrospun nanofibrous mats and their formulation into nanofiber tablets for the modified release of furosemide. Pharmaceutics. 2019;11(9):480. https://doi.org/10.3390/pharmaceutics11090480
• 51. Jeganathan B, Prakya V. Interpolyelectrolyte Complexes of Eudragit® EPO with Hypromellose Acetate Succinate and Eudragit® EPO with Hypromellose Phthalate as Potential Carriers for Oral Controlled Drug Delivery. AAPS PharmSciTech. 2015;16(4):878-88. https://doi.org/10.1208/s12249-014-0252-2
• 52. Alharbi N, Daraei A, Lee H, Guthold M. The effect of molecular weight and fiber diameter on the mechanical properties of single, electrospun PCL nanofibers. Mater. Today Commun. 2023;35:105773. https://doi.org/10.1016/j.mtcomm.2023.105773
• 53. Ding Y, Dou C, Chang S, Xie Z, Yu D-G, Liu Y, Shao J. Core–shell eudragit s100 nanofibers prepared via triaxial electrospinning to provide a colon-targeted extended drug release. Polymers. 2020;12(9):2034. https://doi.org/10.3390/polym12092034
• 54. Abdel-Rahman LM, Eltaher HM, Abdelraouf K, Bahey-El-Din M, Ismail C, Kenawy E-RS, El-Khordagui LK. Vancomycin-functionalized Eudragit-based nanofibers: Tunable drug release and wound healing efficacy. J. Drug Deliv. Sci. Technol. 2020;58:101812. https://doi.org/10.1016/j.jddst.2020.101812
• 55. Pérez-González GL, Villarreal-Gómez LJ, Serrano-Medina A, Torres-Martínez EJ, Cornejo-Bravo JM. Mucoadhesive electrospun nanofibers for drug delivery systems: applications of polymers and the parameters’ roles. Int. J. Nanomed. 2019:5271-85. https://doi.org/10.2147/IJN.S193328
• 56. Cazorla-Luna R, Notario-Pérez F, Martín-Illana A, Bedoya L-M, Tamayo A, Rubio J, et al. Development and In Vitro-Ex Vivo Characterization of Vaginal Mucoadhesive Bilayer Films Based on Ethylcellulose and Biopolymers for Vaginal Sustained Release of Tenofovir. Biomacromolecules. 2020;21(6):2309-19. https://doi.org/10.1021/acs.biomac.0c00249
• 57. Tuğcu-Demiröz F. Vaginal delivery of benzydamine hydrochloride through liposomes dispersed in mucoadhesive gels. Chem. Pharm. Bull. 2017;65(7):660-7. ttps://doi.org/10.1248/cpb.c17-00133
• 58. Müller L, Rosenbaum C, Rump A, Grimm M, Klammt F, Kleinwort A, et al. Determination of Mucoadhesion of Polyvinyl Alcohol Films to Human Intestinal Tissue. Pharmaceutics. 2023;15(6):1740. https://doi.org/10.3390/pharmaceutics15061740
• 59. Thirawong N, Nunthanid J, Puttipipatkhachorn S, Sriamornsak P. Mucoadhesive properties of various pectins on gastrointestinal mucosa: An in vitro evaluation using texture analyzer. Eur. J. Pharm. Biopharm. 2007;67(1):132-40. https://doi.org/10.1016/j.ejpb.2007.01.010