The ever-increasing demands of modern medicine drive the development of novel drug delivery materials. In particular, nanofibers are promising for such materials due to their favorable properties. However, most development is still carried out through laboratory techniques that do not allow extensive and reproducible characterization of materials, which slows medical research. In this work, we focus on the large-scale fabrication and testing of specific antibacterial nanofibrous materials to prevent the postoperative complications associated with the occurrence of bacterial infection. Poly-ε-caprolactone with gentamicin sulfate (antibiotic) in different concentrations was electrospun via a needleless device. The amount of antibiotics was proven by elemental analysis, UV spectrophotometry, and HPLC. The cytocompatibility of the materials was verified in vitro according to ISO 10993-5. The cell adhesion and proliferation were assessed after 2, 7, 14, and 21 days using the CCK-8 metabolic assay, fluorescence, and scanning electron microscopy. The tested nanofiber materials supported cell growth. Antibacterial tests were performed to confirm the release of gentamicin sulfate, and its antibacterial properties were proven toward Staphylococcus gallinarum and Escherichia coli bacteria. The effect of ethylene oxide sterilization was also studied. The sterilized nanofibrous layers are cytocompatible while antibacterial and therefore suitable for medical applications.

Biomedical Center Faculty of Medicine in Pilsen Charles University Alej Svobody 1655 76 Plzen 323 00 Czech Republic

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

Faculty of Mechatronics Informatics and Interdisciplinary Studies Institute of New Technologies and Applied Informatics Studentska 1402 2 Liberec 461 17 Czech Republic

Faculty of Pharmacy The Department of Analytical Chemistry Charles University Akademika Heyrovskeho 1203 Hradec Kralove 500 05 Czech Republic

The Institute for Nanomaterials Advanced Technologies and Innovation Technical University of Liberec Bendlova 7 Liberec 460 01 Czech Republic

Zobrazit více v PubMed

Luraghi A.; Peri F.; Moroni L. Electrospinning for Drug Delivery Applications: A Review. J. Controlled Release 2021, 334, 463–484. 10.1016/j.jconrel.2021.03.033. PubMed DOI

Gunay M. S.; Ozer A. Y.; Chalon S. Drug Delivery Systems for Imaging and Therapy of Parkinson’s Disease. Curr. Neuropharmacol. 2016, 14 (4), 376–391. 10.2174/1570159X14666151230124904. PubMed DOI PMC

Dahlin R. L.; Kasper F. K.; Mikos A. G. Polymeric Nanofibers in Tissue Engineering. Tissue Eng. Part B 2011, 17 (5), 349–364. 10.1089/ten.teb.2011.0238. PubMed DOI PMC

Pisani S.; Dorati R.; Chiesa E.; Genta I.; Modena T.; Bruni G.; Grisoli P.; Conti B. Release Profile of Gentamicin Sulfate from Polylactide-Co-Polycaprolactone Electrospun Nanofiber Matrices. Pharmaceutics 2019, 11 (4), E161.10.3390/pharmaceutics11040161. PubMed DOI PMC

Ceylan M.; Yang S.-Y.; Asmatulu R. Effects of Gentamicin-Loaded PCL Nanofibers on Growth of Gram Positive and Gram Negative Bacteria. Eur. J. Appl. Microbiol. Biotechnol. 2017, 5, 40–51. 10.33500/ijambr.2017.05.005. DOI

Sirc J.; Kubinova S.; Hobzova R.; Stranska D.; Kozlik P.; Bosakova Z.; Marekova D.; Holan V.; Sykova E.; Michalek J. Controlled Gentamicin Release from Multi-Layered Electrospun Nanofibrous Structures of Various Thicknesses. Int. J. Nanomed. 2012, 7, 5315–5325. 10.2147/IJN.S35781. PubMed DOI PMC

Coimbra P.; Freitas J. P.; Gonçalves T.; Gil M. H.; Figueiredo M. Preparation of Gentamicin Sulfate Eluting Fiber Mats by Emulsion and by Suspension Electrospinning. Mater. Sci. Eng.: C 2019, 94, 86–93. 10.1016/j.msec.2018.09.019. PubMed DOI

Abdul Khodir W. K. W.; Abdul Razak A. H.; Ng M. H.; Guarino V.; Susanti D. Encapsulation and Characterization of Gentamicin Sulfate in the Collagen Added Electrospun Nanofibers for Skin Regeneration. J. Funct. Biomater. 2018, 9 (2), E36.10.3390/jfb9020036. PubMed DOI PMC

Rosendorf J.; Horakova J.; Klicova M.; Palek R.; Cervenkova L.; Kural T.; Hosek P.; Kriz T.; Tegl V.; Moulisova V.; Tonar Z.; Treska V.; Lukas D.; Liska V. Experimental Fortification of Intestinal Anastomoses with Nanofibrous Materials in a Large Animal Model. Sci. Rep. 2020, 10 (1), 1–12. 10.1038/s41598-020-58113-4. PubMed DOI PMC

Rosendorf J.; Klicova M.; Cervenkova L.; Horakova J.; Klapstova A.; Hosek P.; Palek R.; Sevcik J.; Polak R.; Treska V.; Chvojka J.; Liska V. Reinforcement of Colonic Anastomosis with Improved Ultrafine Nanofibrous Patch: Experiment on Pig. Biomedicines 2021, 9 (2), 102.10.3390/biomedicines9020102. PubMed DOI PMC

Rosendorf J.; Klicova M.; Cervenkova L.; Palek R.; Horakova J.; Klapstova A.; Hosek P.; Moulisova V.; Bednar L.; Tegl V.; Brzon O.; Tonar Z.; Treska V.; Lukas D.; Liska V. Double-Layered Nanofibrous Patch for Prevention of Anastomotic Leakage and Peritoneal Adhesions, Experimental Study. In Vivo 2021, 35 (2), 731–741. 10.21873/invivo.12314. PubMed DOI PMC

Choi E. J.; Son B.; Hwang T. S.; Hwang E.-H. Increase of Degradation and Water Uptake Rate Using Electrospun Star-Shaped Poly(d,l-Lactide) Nanofiber. J. Ind. Eng. Chem. 2011, 17 (4), 691–695. 10.1016/j.jiec.2010.10.024. DOI

Kamath S. M.; Sridhar K.; Jaison D.; Gopinath V.; Ibrahim B. K. M.; Gupta N.; Sundaram A.; Sivaperumal P.; Padmapriya S.; Patil S. S. Fabrication of Tri-Layered Electrospun Polycaprolactone Mats with Improved Sustained Drug Release Profile. Sci. Rep 2020, 10 (1), 18179.10.1038/s41598-020-74885-1. PubMed DOI PMC

Klicova M.; Klapstova A.; Chvojka J.; Koprivova B.; Jencova V.; Horakova J. Novel Double-Layered Planar Scaffold Combining Electrospun PCL Fibers and PVA Hydrogels with High Shape Integrity and Water Stability. Mater. Lett. 2020, 263, 12728110.1016/j.matlet.2019.127281. DOI

Liu Q.; Ouyang W.-C.; Zhou X.-H.; Jin T.; Wu Z.-W. Antibacterial Activity and Drug Loading of Moxifloxacin-Loaded Poly(Vinyl Alcohol)/Chitosan Electrospun Nanofibers. Front. Mater. 2021, 82, 64342810.3389/fmats.2021.643428. DOI

Wei Z.; Wang L.; Zhang S.; Chen T.; Yang J.; Long S.; Wang X. Electrospun Antibacterial Nanofibers for Wound Dressings and Tissue Medicinal Fields: A Review. J. Innov. Opt. Health Sci. 2020, 13 (05), 2030012.10.1142/S1793545820300128. DOI

Gao Y.; Truong Y. B.; Zhu Y.; Kyratzis I. L. Electrospun Antibacterial Nanofibers: Production, Activity, and in Vivo Applications. J. Appl. Polym. Sci. 2014, 131 (18), 9041.10.1002/app.40797. DOI

Ali I. H.; Ouf A.; Elshishiny F.; Taskin M. B.; Song J.; Dong M.; Chen M.; Siam R.; Mamdouh W. Antimicrobial and Wound-Healing Activities of Graphene-Reinforced Electrospun Chitosan/Gelatin Nanofibrous Nanocomposite Scaffolds. ACS Omega 2022, 7 (2), 1838–1850. 10.1021/acsomega.1c05095. PubMed DOI PMC

Schardey H. M.; Rogers S.; Schopf S. K.; von Ahnen T.; Wirth U. Are Gut Bacteria Associated with the Development of Anastomotic Leaks?. Coloproctology 2017, 39 (2), 94–100. 10.1007/s00053-016-0136-x. DOI

Kadurugamuwa J. L.; Clarke A. J.; Beveridge T. J. Surface Action of Gentamicin on Pseudomonas Aeruginosa. J. Bacteriol. 1993, 175 (18), 5798–5805. 10.1128/jb.175.18.5798-5805.1993. PubMed DOI PMC

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, 10577310.1016/j.mtcomm.2023.105773. DOI

Bacakova L.; Filova E.; Parizek M.; Ruml T.; Svorcik V. Modulation of Cell Adhesion, Proliferation and Differentiation on Materials Designed for Body Implants. Biotechnol. Adv. 2011, 29 (6), 739–767. 10.1016/j.biotechadv.2011.06.004. PubMed DOI

Ismail A. F. H.; Mohamed F.; Rosli L. M. M.; Shafri M. A. M.; Haris M. S.; Adina A. B. Spectrophotometric Determination of Gentamicin Loaded PLGA Microparticles and Method Validation via Ninhydrin-Gentamicin Complex As A Rapid Quantification Approach. J. Appl. Pharm. Sci. 2016, 6, 007–014. 10.7324/JAPS.2016.600102. DOI

Kuang G.; Zhang Z.; Liu S.; Zhou D.; Lu X.; Jing X.; Huang Y. Biphasic Drug Release from Electrospun Polyblend Nanofibers for Optimized Local Cancer Treatment. Biomater. Sci. 2018, 6 (2), 324–331. 10.1039/C7BM01018D. PubMed DOI

Kajdič S.; Planinšek O.; Gašperlin M.; Kocbek P. Electrospun Nanofibers for Customized Drug-Delivery Systems. J. Drug Delivery Sci. Technol. 2019, 51, 672–681. 10.1016/j.jddst.2019.03.038. DOI

Mendes G. C. C.; Brandão T. R. S.; Silva C. L. M. Ethylene Oxide Sterilization of Medical Devices: A Review. Am. J. Infect. Control 2007, 35 (9), 574–581. 10.1016/j.ajic.2006.10.014. PubMed DOI

Horakova J.; Mikes P.; Saman A.; Jencova V.; Klapstova A.; Svarcova T.; Ackermann M.; Novotny V.; Suchy T.; Lukas D. The Effect of Ethylene Oxide Sterilization on Electrospun Vascular Grafts Made from Biodegradable Polyesters. Mater. Sci. Eng. C 2018, 92, 132–142. 10.1016/j.msec.2018.06.041. PubMed DOI

Horakova J.; Klicova M.; Erben J.; Klapstova A.; Novotny V.; Behalek L.; Chvojka J. Impact of Various Sterilization and Disinfection Techniques on Electrospun Poly-ε-Caprolactone. ACS Omega 2020, 5 (15), 8885–8892. 10.1021/acsomega.0c00503. PubMed DOI PMC

Friess W.; Schlapp M. Sterilization of Gentamicin Containing Collagen/PLGA Microparticle Composites. Eur. J. Pharm. Biopharm. 2006, 63 (2), 176–187. 10.1016/j.ejpb.2005.11.007. PubMed DOI

Dhal C.; Mishra R. In Vitro and in Vivo Evaluation of Gentamicin Sulphate-Loaded PLGA Nanoparticle-Based Film for the Treatment of Surgical Site Infection. Drug Delivery Transl. Res. 2020, 10 (4), 1032–1043. 10.1007/s13346-020-00730-7. PubMed DOI

Mullins N. D.; Deadman B. J.; Moynihan H. A.; McCarthy F. O.; Lawrence S. E.; Thompson J.; Maguire A. R. The Impact of Storage Conditions upon Gentamicin Coated Antimicrobial Implants. J. Pharm. Anal. 2016, 6 (6), 374–381. 10.1016/j.jpha.2016.05.002. PubMed DOI PMC