title: Formulation and evaluation of chitosan/polyethylene oxide nanofibers loaded with metronidazole for local infections.
abstract: Nanofibers combined with an antimicrobial represent a powerful strategy for treatment of various infections. Local infections usually have a low fluid volume available for drug release, whereas pharmacopoeian dissolution tests include a much larger receptor volume. Therefore, the development of novel drug-release methods that more closely resemble the in-vivo conditions is necessary. We first developed novel biocompatible and biodegradable chitosan/polyethylene oxide nanofibers using environmentally friendly electrospinning of aqueous polymer solutions, with the inclusion of the antimicrobial metronidazole. Here, the focus is on the characterization of these nanofibers, which have high potential for bioadhesion and retention at the site of application. These can be used where prolonged retention of the delivery system at an infected target site is needed. Drug release was studied using three in-vitro methods: a dissolution apparatus (Apparatus 1 of the European Pharmacopoeia), vials, and a Franz diffusion cell. In contrast to other studies, here the Franz diffusion cell method was modified to introduce a small volume of medium with the nanofibers in the donor compartment, where the nanofibers swelled, eroded, and released the metronidazole, which then diffused into the receptor compartment. This set-up with nanofibers in a limited amount of medium released the drug more slowly compared to the other two in-vitro methods that included larger volumes of medium. These findings show that drug release from nanofibers strongly depends on the release method used. Therefore, in-vitro test methods should closely resemble the in-vivo conditions for more accurate prediction of drug release at a therapeutic site.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia. Electronic address: spela.zupancic@ffa.uni-lj.si.
authors.forename: Špela
authors.initials: Š
authors.lastname: Zupančič
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia. Electronic address: tanja.potrc@ffa.uni-lj.si.
authors.forename: Tanja
authors.initials: T
authors.lastname: Potrč
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia.
authors.forename: Saša
authors.initials: S
authors.lastname: Baumgartner
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia. Electronic address: petra.kocbek@ffa.uni-lj.si.
authors.forename: Petra
authors.initials: P
authors.lastname: Kocbek
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia. Electronic address: julijana.kristl@ffa.uni-lj.si.
authors.forename: Julijana
authors.initials: J
authors.lastname: Kristl
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D048271:Chitosan / Q000737:chemistry*; D016503:Drug Delivery Systems; D008795:Metronidazole / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D057139:Nanofibers / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D000890:Anti-Infective Agents; D008795:Metronidazole; D011092:Polyethylene Glycols; D048271:Chitosan
keywords: Antibiotic; Chronic wounds; Drug release method; Electrospinning; Nanofibers; Periodontal disease