This study investigates the influence of solvent systems on incorporating the hydrophilic drug mitomycin C (MMC) into electrospun polyvinylidene fluoride (PVDF) nanofibers, with a focus on the often-overlooked issue of active substance degradation during storage. MMC was dissolved in either water or acetone and added to the electrospinning solution, followed by quantification of drug loading using liquid chromatography. Dissolution of MMC in water resulted in poor drug loading efficiency. In contrast, acetone led to significantly higher incorporation, with 50.66% loading for PVDF containing 0.01% MMC and 26.63% for PVDF with 0.1% MMC. However, storage at 4 °C over 21 days resulted in a substantial decline in MMC content, indicating challenges in long-term stability. In vitro testing using mouse fibroblasts revealed no cytotoxic effects of the nanofibrous layers and demonstrated a reduction in fibroblast proliferation in MMC-loaded samples compared to pure PVDF controls. These findings highlight the importance of solvent selection for effective drug incorporation and point to the potential of PVDF-based nanofibers for antifibrotic applications.

Faculty of Textile Engineering Department of Nonwovens and Nanofibrous Materials Technical University of Liberec Studentska 1402 2 461 17 Liberec Czech Republic

Institute for Nanomaterials Advanced Technologies and Innovations Technical University of Liberec Studentska 1402 2 461 17 Liberec Czech Republic

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Gaydhane M. K., Sharma C. S., Majumdar S.. Electrospun Nanofibres in Drug Delivery: Advances in Controlled Release Strategies. RSC Adv. 2023;13(11):7312–7328. doi: 10.1039/D2RA06023J. PubMed DOI PMC

Farhaj S., Conway B. R., Ghori M. U.. Nanofibres in Drug Delivery Applications. Fibers. 2023;11(2):21. doi: 10.3390/fib11020021. DOI

Josyula A., Mozzer A., Szeto J., Ha Y., Richmond N., Chung S. W., Rompicharla S. V. K., Narayan J., Ramesh S., Hanes J., Ensign L., Parikh K., Pitha I.. Nanofiber-based Glaucoma Drainage Implant Improves Surgical Outcomes by Modulating Fibroblast Behavior. Bioeng. Transl. Med. 2023;8(3):e10487. doi: 10.1002/btm2.10487. PubMed DOI PMC

Parikh K. S., Josyula A., Omiadze R., Ahn J. Y., Ha Y., Ensign L. M., Hanes J., Pitha I.. Nano-Structured Glaucoma Drainage Implant Safely and Significantly Reduces Intraocular Pressure in Rabbits via Post-Operative Outflow Modulation. Sci. Rep. 2020;10(1):12911. doi: 10.1038/s41598-020-69687-4. PubMed DOI PMC

Klapstova A., Horakova J., Tunak M., Shynkarenko A., Erben J., Hlavata J., Bulir P., Chvojka J.. A PVDF Electrospun Antifibrotic Composite for Use as a Glaucoma Drainage Implant. Mater. Sci. Eng., C. 2021;119:111637. doi: 10.1016/j.msec.2020.111637. PubMed DOI

Dong A., Han L., Shao Z., Fan P., Zhou X., Yuan H.. Glaucoma Drainage Device Coated with Mitomycin C Loaded Opal Shale Microparticles to Inhibit Bleb Fibrosis. ACS Appl. Mater. Interfaces. 2019;11(10):10244–10253. doi: 10.1021/acsami.8b18551. PubMed DOI

Sahiner N., Kravitz D. J., Qadir R., Blake D. A., Haque S., John V. T., Margo C. E., Ayyala R. S.. Creation of a Drug-Coated Glaucoma Drainage Device Using Polymer Technology: In Vitro and In Vivo Studies. Arch. Ophthalmol. 2009;127(4):448–453. doi: 10.1001/archophthalmol.2009.19. PubMed DOI

Concha V. O. C., Timóteo L., Duarte L. A. N., Bahú J. O., Munoz F. L., Silva A. P., Lodi L., Severino P., León-Pulido J., Souto E. B.. Properties Characterization and Biomedical Applications of Polyvinylidene Fluoride (PVDF): A Review. J. Mater. Sci. 2024;59(31):14185–14204. doi: 10.1007/s10853-024-10046-3. DOI

Pourmadadi M., Ahmari A., Mirshafiei M., Omrani Z., Yazdian F., Rahdar A., Fathi-karkan S., Aboudzadeh M. A.. Polyvinylidene Fluoride in Biomedical Applications: Properties, Challenges, and Future Prospects. Eur. Polym. J. 2025;231:113889. doi: 10.1016/j.eurpolymj.2025.113889. DOI

Mohajeri A., Amigh S.. In the Search of Active Nanocarriers for Delivery of Mitomycin C Drug. Mater. Adv. 2020;1(6):1909–1919. doi: 10.1039/D0MA00018C. DOI

Pourmadadi M., Ghaemi A., Shaghaghi M., Naderian N., Yazdian F., Rahdar A., Romanholo Ferreira L. F.. Macromolecules and Nanomaterials Loaded with Mitomycin C as Promising New Treatment Option Cancer Drug Nanoformulation: A Literature Review. J. Drug Delivery Sci. Technol. 2023;87:104835. doi: 10.1016/j.jddst.2023.104835. DOI

Wilkins M., Indar A., Wormald R.. Intraoperative Mitomycin C for Glaucoma Surgery. Cochrane Database Syst. Rev. 2005;2010(2):CD002897. doi: 10.1002/14651858.CD002897.pub2. PubMed DOI PMC

Abraham L. M., Selva D., Casson R., Leibovitch I.. Mitomycin. Drugs. 2006;66(3):321–340. doi: 10.2165/00003495-200666030-00005. PubMed DOI

Beijnen J. H., van Gijn R., Underberg W. J.. Chemical Stability of the Antitumor Drug Mitomycin C in Solutions for Intravesical Instillation. J. Parenter. Sci. Technol. Publ. Parenter. Drug Assoc. 1990;44(6):332–335. PubMed

Shi R., Huang Y., Zhang J., Wu C., Gong M., Tian W., Zhang L.. Effective Delivery of Mitomycin-C and Meloxicam by Double-Layer Electrospun Membranes for the Prevention of Epidural Adhesions. J. Biomed. Mater. Res. B Appl. Biomater. 2020;108(2):353–366. doi: 10.1002/jbm.b.34394. PubMed DOI

Zhao X., Jiang S., Liu S., Chen S., Lin Z. Y., Pan G., He F., Li F., Fan C., Cui W.. Optimization of Intrinsic and Extrinsic Tendon Healing through Controllable Water-Soluble Mitomycin-C Release from Electrospun Fibers by Mediating Adhesion-Related Gene Expression. Biomaterials. 2015;61:61–74. doi: 10.1016/j.biomaterials.2015.05.012. PubMed DOI

Hashem H. M., Motawea A., Kamel A. H., Bary E. M. A., Hassan S. S. M.. Fabrication and Characterization of Electrospun Nanofibers Using Biocompatible Polymers for the Sustained Release of Venlafaxine. Sci. Rep. 2022;12(1):18037. doi: 10.1038/s41598-022-22878-7. PubMed DOI PMC

Ghasemvand F., Kabiri M., Hassan-Zadeh V., Simchi A.. Chitosan, Polyethylene Oxide/Polycaprolactone Electrospun Core/Shell Nanofibrous Mat Containing Rosuvastatin as a Novel Drug Delivery System for Enhancing Human Mesenchymal Stem Cell Osteogenesis. Front. Mol. Biosci. 2023;10:1220357. doi: 10.3389/fmolb.2023.1220357. PubMed DOI PMC

Geyik F., Kaya S., Yılmaz D. E., Demirci H., Akmayan I. ˙., Özbek T., Acar S.. Propolis-Loaded Poly­(Lactic-Co-Glycolic Acid) Nanofibers: An In Vitro Study. ACS Omega. 2024;9(12):14054–14062. doi: 10.1021/acsomega.3c09492. PubMed DOI PMC

ISO 10993-5, 2009. https://www.iso.org/standard/36406.html (accessed Apr 14, 2025).

ISO 10993-7, 2008. https://www.iso.org/standard/34213.html (accessed Apr 17, 2025).

Aghayari S.. PVDF Composite Nanofibers Applications. Heliyon. 2022;8(11):e11620. doi: 10.1016/j.heliyon.2022.e11620. PubMed DOI PMC

Durán-Rey D., Brito-Pereira R., Ribeiro C., Ribeiro S., Sánchez-Margallo J. A., Crisóstomo V., Irastorza I., Silván U., Lanceros-Méndez S., Sánchez-Margallo F. M.. Development and Evaluation of Different Electroactive Poly­(Vinylidene Fluoride) Architectures for Endothelial Cell Culture. Front. Bioeng. Biotechnol. 2022;10:1044667. doi: 10.3389/fbioe.2022.1044667. PubMed DOI PMC

Bagherzadeh E., Sherafat Z., Zebarjad S. M., Khodaei A., Yavari S. A.. Stimuli-Responsive Piezoelectricity in Electrospun Polycaprolactone (PCL)/Polyvinylidene Fluoride (PVDF) Fibrous Scaffolds for Bone Regeneration. J. Mater. Res. Technol. 2023;23:379–390. doi: 10.1016/j.jmrt.2023.01.007. DOI

Zaszczyńska A., Gradys A., Ziemiecka A., Szewczyk P. K., Tymkiewicz R., Lewandowska-Szumieł M., Stachewicz U., Sajkiewicz P. Ł.. Enhanced Electroactive Phases of Poly­(Vinylidene Fluoride) Fibers for Tissue Engineering Applications. Int. J. Mol. Sci. 2024;25(9):4980. doi: 10.3390/ijms25094980. PubMed DOI PMC

Yin J.-Y., Boaretti C., Lorenzetti A., Martucci A., Roso M., Modesti M.. Effects of Solvent and Electrospinning Parameters on the Morphology and Piezoelectric Properties of PVDF Nanofibrous Membrane. Nanomaterials. 2022;12(6):962. doi: 10.3390/nano12060962. PubMed DOI PMC

Nuamcharoen P., Kobayashi T., Potiyaraj P.. Influence of Volatile Solvents and Mixing Ratios of Binary Solvent Systems on Morphology and Performance of Electrospun Poly­(Vinylidene Fluoride) Nanofibers. Polym. Int. 2021;70(10):1465–1477. doi: 10.1002/pi.6218. DOI

Li Y., Zhu J., Cheng H., Li G., Cho H., Jiang M., Gao Q., Zhang X.. Developments of Advanced Electrospinning Techniques: A Critical Review. Adv. Mater. Technol. 2021;6(11):2100410. doi: 10.1002/admt.202100410. DOI

Bonakdar M. A., Rodrigue D.. Electrospinning: Processes, Structures, and Materials. Macromol. 2024;4(1):58–103. doi: 10.3390/macromol4010004. DOI

Sarma S., Gaur C., Benarrait R., Haus J. N., Koch E., Dietzel A.. Prediction of Bead Formation in PVDF Fiber across Different Solvent Systems Using Interpretable Machine Learning. Polymer. 2025;317:127972. doi: 10.1016/j.polymer.2024.127972. DOI

Patel R. K., Jonnalagadda S., Gupta P. K.. Use of Flory-Huggins Interaction Parameter and Contact Angle Values to Predict the Suitability of the Drug-Polymer System for the Production and Stability of Nanosuspensions. Pharm. Res. 2022;39(5):1001–1017. doi: 10.1007/s11095-022-03269-z. PubMed DOI

Milczewska K., Voelkel A., Zwolińska J., Jędro D.. Preparation of Hybrid Materials for Controlled Drug Release. Drug Dev. Ind. Pharm. 2016;42(7):1058–1065. doi: 10.3109/03639045.2015.1107092. PubMed DOI

Wang F., Altschuh P., Ratke L., Zhang H., Selzer M., Nestler B.. Progress Report on Phase Separation in Polymer Solutions. Adv. Mater. 2019;31(26):1806733. doi: 10.1002/adma.201806733. PubMed DOI

Molekula Group . (17545348) Mitomycin C [50–07–7], Molekula Group. https://molkula.com/catalog/50-07-7/17545348-mitomycin-c (accessed May 26, 2025).

Böncü T. E., Ozdemir N.. Effects of Drug Concentration and PLGA Addition on the Properties of Electrospun Ampicillin Trihydrate-Loaded PLA Nanofibers. Beilstein J. Nanotechnol. 2022;13(1):245–254. doi: 10.3762/bjnano.13.19. PubMed DOI PMC

Chen T., Kunnavatana S. S., Koch R. J.. Effects of Mitomycin-C on Normal Dermal Fibroblasts. Laryngoscope. 2006;116(4):514–517. doi: 10.1097/01.MLG.0000205590.62824.0A. PubMed DOI

Blake D. A., Sahiner N., John V. T., Clinton A. D., Galler K. E., Walsh M., Arosemena A., Johnson P. Y., Ayyala R. S.. Inhibition of Cell Proliferation by Mitomycin C Incorporated into P­(HEMA) Hydrogels. J. Glaucoma. 2006;15(4):291. doi: 10.1097/01.ijg.0000212236.96039.9c. PubMed DOI