{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:39:36Z","timestamp":1792273176369,"version":"4.4.0"},"reference-count":36,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,25]],"date-time":"2024-08-25T00:00:00Z","timestamp":1724544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research, Development, and Innovation Fund","award":["\u00daNKP-23-4-II-SE-22"],"award-info":[{"award-number":["\u00daNKP-23-4-II-SE-22"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A novel ophthalmic delivery system utilizing levofloxacin-loaded, preservative-free, nanofiber-based inserts was investigated. Polyvinyl alcohol (PVA) and Poloxamer 407 (Polox)were employed as matrix materials, while hydroxypropyl-beta-cyclodextrin (HP-\u03b2-CD) was a solubilizer. The formulations were prepared via electrospinning and characterized for fiber morphology, drug dissolution, cytotoxicity, and antimicrobial activity. Scanning electron microscopy confirmed uniform fibrous structures. Fourier Transform Infrared spectroscopy and X-ray diffraction analyses demonstrated the amorphous state of levofloxacin within the fibers. In vitro dissolution studies revealed a rapid (within 2 min) and complete drug release, with higher HP-\u03b2-CD levels slightly delaying the release. Cytotoxicity tests showed increased HP-\u03b2-CD concentrations induced irritation, that was mitigated by sodium hyaluronate. The antimicrobial efficacy of the nanofibers was comparable to conventional eye drops, with lower minimum inhibitory concentrations for most tested strains. The nanofibrous formulation prepared from a PVA\u2013Polox-based viscous solution of the drug:CD 1:1 mol ratio, containing 0.4% (w\/w) sodium hyaluronate) was identified as a particularly promising alternative formulation due to its rapid and complete dissolution, good biocompatibility, and effective antimicrobial properties. Its gelling properties indicate that the residence time on the eye surface can be increased, potentially reducing discomfort and enhancing therapeutic outcomes. The nanofibrous formulations enhanced antimicrobial efficacy, providing a preservative-free alternative that minimizes the potential eye irritation that might occur because of the preservative agent and reduces the administrated dose frequency by extending the drug\u2019s retention time on the eye\u2019s surface. Subsequently, it improves patients\u2019 adherence, which would reflect positively on the bioavailability. The levofloxacin-HP-\u03b2-CD nanofibers demonstrate promise as an alternative to traditional eye drops, offering advantages in solubility, stability, and patient compliance for ocular infection treatment.<\/jats:p>","DOI":"10.3390\/ijms25179228","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T07:53:37Z","timestamp":1724658817000},"page":"9228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Formulation and Development of Nanofiber-Based Ophthalmic Insert for the Treatment of Bacterial Conjunctivitis"],"prefix":"10.3390","volume":"25","author":[{"given":"Eszter","family":"Farkas","sequence":"first","affiliation":[{"name":"Center of Pharmacology and Drug Research & Development, University Pharmacy Department of Pharmacy Administration, Semmelweis University, H\u0151gyes Endre Street 7-9, H-1092 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houssam","family":"Abboud","sequence":"additional","affiliation":[{"name":"Center of Pharmacology and Drug Research & Development, University Pharmacy Department of Pharmacy Administration, Semmelweis University, H\u0151gyes Endre Street 7-9, H-1092 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6223-5214","authenticated-orcid":false,"given":"N\u00e1ndor","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology Semmelweis University, T\u0171zolt\u00f3 Street 58, H-1094 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1lint","family":"Hofmeister","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Semmelweis University, Nagyv\u00e1rad Square 4, H-1089 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eszter","family":"Ostorh\u00e1zi","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Semmelweis University, Nagyv\u00e1rad Square 4, H-1089 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bence","family":"T\u00f3th","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Semmelweis University, H\u0151gyes Endre Street 7, H-1092 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bal\u00e1zs","family":"Pinke","sequence":"additional","affiliation":[{"name":"Department of Polymer Engineering, Faculty of Mechanical Engineering, Budapest University of Technology and Economics, M\u0171egyetem Rkp. 3, H-1111 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5979-7403","authenticated-orcid":false,"given":"L\u00e1szl\u00f3","family":"M\u00e9sz\u00e1ros","sequence":"additional","affiliation":[{"name":"Department of Polymer Engineering, Faculty of Mechanical Engineering, Budapest University of Technology and Economics, M\u0171egyetem Rkp. 3, H-1111 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5419-9137","authenticated-orcid":false,"given":"Rom\u00e1na","family":"Zelk\u00f3","sequence":"additional","affiliation":[{"name":"Center of Pharmacology and Drug Research & Development, University Pharmacy Department of Pharmacy Administration, Semmelweis University, H\u0151gyes Endre Street 7-9, H-1092 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2648-3037","authenticated-orcid":false,"given":"Adrienn","family":"Kazsoki","sequence":"additional","affiliation":[{"name":"Center of Pharmacology and Drug Research & Development, University Pharmacy Department of Pharmacy Administration, Semmelweis University, H\u0151gyes Endre Street 7-9, H-1092 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1097\/ICO.0000000000001486","article-title":"Clinical Features, Antibiotic Susceptibility Profile, and Outcomes of Infectious Keratitis Caused by Stenotrophomonas maltophilia","volume":"37","author":"Palioura","year":"2018","journal-title":"Cornea"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.jtos.2017.06.001","article-title":"Review: Emerging strategies for antimicrobial drug delivery to the ocular surface: Implications for infectious keratitis","volume":"15","author":"Sharma","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1159\/000357976","article-title":"Effects of Fluoroquinolone Eye Solutions without Preservatives on Human Corneal Epithelial Cells in vitro","volume":"51","author":"Oum","year":"2014","journal-title":"Ophthalmic Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1185\/030079908X261005","article-title":"Intrinsic cytotoxic effects of fluoroquinolones on human corneal keratocytes and endothelial cells","volume":"24","author":"Bezwada","year":"2008","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.2165\/00003495-200969090-00009","article-title":"Levofloxacin 0.5% Ophthalmic Solution","volume":"69","author":"Keating","year":"2009","journal-title":"Drugs"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1080\/03639045.2020.1750626","article-title":"Eye drops and eye gels of levofloxacin: Comparison of ocular absorption characterizations and therapeutic effects in the treatment of bacterial keratitis in rabbits","volume":"46","author":"Li","year":"2020","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1016\/j.jcrs.2014.02.037","article-title":"Evaluation of eyedrop administration by inexperienced patients after cataract surgery","volume":"40","author":"An","year":"2014","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s10792-010-9362-3","article-title":"Electronic compliance monitoring of topical treatment after ophthalmic surgery","volume":"30","author":"Hermann","year":"2010","journal-title":"Int. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Addo, R.T. (2016). Background of Ocular Drug Delivery. Ocular Drug Delivery: Advances, Challenges and Applications, Springer International Publishing.","DOI":"10.1007\/978-3-319-47691-9"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1208\/s12249-021-01977-0","article-title":"Review of Approaches for Increasing Ophthalmic Bioavailability for Eye Drop Formulations","volume":"22","author":"Lanier","year":"2021","journal-title":"AAPS PharmSciTech"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.ijpharm.2007.03.011","article-title":"Nanosuspension as an ophthalmic delivery system for certain glucocorticoid drugs","volume":"340","author":"Kassem","year":"2007","journal-title":"Int. J. Pharm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.actbio.2018.11.020","article-title":"Bioinspired hydrogels for drug-eluting contact lenses","volume":"84","author":"Concheiro","year":"2019","journal-title":"Acta Biomater."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1007\/s13346-020-00843-z","article-title":"Corticosteroids in ophthalmology: Drug delivery innovations, pharmacology, clinical applications, and future perspectives","volume":"11","author":"Gaballa","year":"2021","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kim, H.M., and Woo, S.J. (2021). Ocular Drug Delivery to the Retina: Current Innovations and Future Perspectives. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13010108"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"121090","DOI":"10.1016\/j.ijpharm.2021.121090","article-title":"Advances and challenges in the nanoparticles-laden contact lenses for ocular drug delivery","volume":"608","author":"Maulvi","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Terreni, E., Burgalassi, S., Chetoni, P., Tampucci, S., Zucchetti, E., Fais, R., Ghelardi, E., Lupetti, A., and Monti, D. (2020). Development and Characterization of a Novel Peptide-Loaded Antimicrobial Ocular Insert. Biomolecules, 10.","DOI":"10.3390\/biom10050664"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"122911","DOI":"10.1016\/j.ijpharm.2023.122911","article-title":"Hyaluronic acid\u2013PVA films for the simultaneous delivery of dexamethasone and levofloxacin to ocular tissues","volume":"638","author":"Ghezzi","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"409","DOI":"10.3109\/1061186X.2010.504268","article-title":"Biodegradable levofloxacin nanoparticles for sustained ocular drug delivery","volume":"19","author":"Gupta","year":"2011","journal-title":"J. Drug Target."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e08697","DOI":"10.1016\/j.heliyon.2021.e08697","article-title":"Development of topical chitosan\/\u03b2-glycerophosphate-based hydrogel loaded with levofloxacin in the treatment of keratitis: An ex-vivo study","volume":"8","author":"Chang","year":"2022","journal-title":"Heliyon"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.ijbiomac.2017.11.170","article-title":"Formulation and optimization of levofloxacin loaded chitosan nanoparticle for ocular delivery: In-vitro characterization, ocular tolerance and antibacterial activity","volume":"108","author":"Ameeduzzafar","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1080\/10837450.2019.1602631","article-title":"Formulation of sustained release bioadhesive minitablets containing solid dispersion of levofloxacin for once daily ocular use","volume":"24","year":"2019","journal-title":"Pharm. Dev. Technol."},{"key":"ref_22","first-page":"292","article-title":"Improvement of Ocular Efficacy of Levofloxacin by Bioadhesive Chitosan Coated PLGA Nanoparticles: Box-behnken Design, In-vitro Characterization, Antibacterial Evaluation and Scintigraphy Study","volume":"19","author":"Ameeduzzafar","year":"2020","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"De Gaetano, F., Marino, A., Marchetta, A., Bongiorno, C., Zagami, R., Cristiano, M.C., Paolino, D., Pistar\u00e0, V., and Ventura, C.A. (2021). Development of Chitosan\/Cyclodextrin Nanospheres for Levofloxacin Ocular Delivery. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13081293"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1080\/03639045.2019.1698598","article-title":"Preparation of levofloxacin loaded in situ gel for sustained ocular delivery: In vitro and ex vivo evaluations","volume":"46","author":"Jain","year":"2020","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"118688","DOI":"10.1016\/j.ijpharm.2019.118688","article-title":"Thermosensitive glycol chitosan-based hydrogel as a topical ocular drug delivery system for enhanced ocular bioavailability","volume":"570","author":"Shi","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"120676","DOI":"10.1016\/j.ijpharm.2021.120676","article-title":"Development and optimization of hot-melt extruded moxifloxacin hydrochloride inserts, for ocular applications, using the design of experiments","volume":"603","author":"Thakkar","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"119552","DOI":"10.1016\/j.ijpharm.2020.119552","article-title":"Development of besifloxacin HCl loaded nanofibrous ocular inserts for the treatment of bacterial keratitis: In vitro, ex vivo and in vivo evaluation","volume":"585","author":"Polat","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1016\/j.polymer.2006.02.046","article-title":"Crosslinking of the electrospun gelatin nanofibers","volume":"47","author":"Zhang","year":"2006","journal-title":"Polymer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1080\/02713683.2018.1563196","article-title":"Development of Nanofibrous Ocular Insert for Retinal Delivery of Fluocinolone Acetonide","volume":"44","author":"Singla","year":"2019","journal-title":"Curr. Eye Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"014108","DOI":"10.1088\/1468-6996\/11\/1\/014108","article-title":"Electrospun nanofibrous materials for tissue engineering and drug delivery","volume":"11","author":"Cui","year":"2010","journal-title":"Sci. Technol. Adv. Mater."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Fan, J., Li, G., Deng, S., and Wang, Z. (2019). Mechanical Properties and Microstructure of Polyvinyl Alcohol (PVA) Modified Cement Mortar. Appl. Sci., 9.","DOI":"10.3390\/app9112178"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1517\/17425247.2013.796360","article-title":"Applications of poloxamers in ophthalmic pharmaceutical formulations: An overview","volume":"10","author":"Almeida","year":"2013","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Miranda, G.M., Santos, V.O., Bessa, J.R., Teles, Y.C.F., Yahou\u00e9d\u00e9hou, S.C., Goncalves, M.S., and Ribeiro-Filho, J. (2021). Inclusion Complexes of Non-Steroidal Anti-Inflammatory Drugs with Cyclodextrins: A Systematic Review. Biomolecules, 11.","DOI":"10.3390\/biom11030361"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Grassiri, B., Knoll, P., Fabiano, A., Piras, A.M., Zambito, Y., and Bernkop-Schn\u00fcrch, A. (2022). Thiolated Hydroxypropyl-\u03b2-cyclodextrin: A Potential Multifunctional Excipient for Ocular Drug Delivery. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052612"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.apsb.2011.10.004","article-title":"Doxycycline and hydroxypropyl-\u03b2-cyclodextrin complex in poloxamer thermal sensitive hydrogel for ophthalmic delivery","volume":"1","author":"He","year":"2011","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/0278-6915(85)90030-4","article-title":"Hen\u2019s egg chorioallantoic membrane test for irritation potential","volume":"23","author":"Luepke","year":"1985","journal-title":"Food Chem. Toxicol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/17\/9228\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:42:32Z","timestamp":1760110952000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/17\/9228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,25]]},"references-count":36,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ijms25179228"],"URL":"https:\/\/doi.org\/10.3390\/ijms25179228","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,25]]}}}