title: Polymeric Nanofiber/Antifungal Formulations Using a Novel Co-extrusion Approach.
abstract: We report the successful implementation of a novel melt co-extrusion process to fabricate ca. 1 μm diameter fibers of poly(caprolactone) (PCL) containing the antifungal compound clotrimazole in concentrations between 4 and 8 wt%. The process involves co-extrusion of a clotrimazole-loaded PCL along with poly(ethylene oxide) (PEO) as a co-feed, with subsequent removal of PEO to isolate PCL-clotrimazole fibers. In vitro tests of the clotrimazole-containing fibers against the fungus Aspergillus fumigatus, Candida albicans, and Trichophyton mentagrophytes strains demonstrated good antifungal activity which was maintained for more than 3 weeks. An in vivo study using a mouse model showed the lowest tissue fungal burden for PCL-clotrimazole when compared to a PCL-only patch and untreated controls. Comparative studies were conducted with clotrimazole-containing PCL fibers fabricated by electrospinning. Our data showed that the co-extruded, clotrimazole-containing fibers maintain activity for longer times vs. electrospun samples. This, coupled with the much higher throughput of the co-extrusion process vs. electrospinning, renders this new approach very attractive for the fabrication of drug-releasing polymer fibers.
authors.affiliation: Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, Ohio, 44106, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Mofidfar
authors.affiliation: Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, Ohio, 44106, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Dermatology and Center for Medical Mycology, Case Western Reserve University, Cleveland, Ohio, 44106, USA.|University Hospitals Case Medical Center, Cleveland, Ohio, 44106, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Long
authors.affiliation: Department of Dermatology and Center for Medical Mycology, Case Western Reserve University, Cleveland, Ohio, 44106, USA.|University Hospitals Case Medical Center, Cleveland, Ohio, 44106, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Hager
authors.affiliation: Department of Ophthalmology and Visual Science, Case Western Reserve University, Cleveland, Ohio, 44106, USA.
authors.forename: Chairut
authors.initials: C
authors.lastname: Vareechon
authors.affiliation: Institute for Immunology, Physiology & Biophysics, School of Medicine, University of California, Irvine, California, 92697, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Pearlman
authors.affiliation: Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, Ohio, 44106, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Baer
authors.affiliation: Department of Dermatology and Center for Medical Mycology, Case Western Reserve University, Cleveland, Ohio, 44106, USA. mahmoud.ghannoum@case.edu.|University Hospitals Case Medical Center, Cleveland, Ohio, 44106, USA. mahmoud.ghannoum@case.edu.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Ghannoum
authors.affiliation: Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, Ohio, 44106, USA. gew5@case.edu.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Wnek
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D002176:Candida albicans / Q000187:drug effects / Q000378:metabolism; D002208:Caproates / Q000737:chemistry / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003022:Clotrimazole / Q000737:chemistry / Q000493:pharmacokinetics; D004339:Drug Compounding; D065546:Drug Liberation / Q000187:drug effects / Q000502:physiology; D007783:Lactones / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D057139:Nanofibers / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics; D011108:Polymers / Q000737:chemistry* / Q000493:pharmacokinetics; D014249:Trichophyton / Q000187:drug effects / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D002208:Caproates; D007783:Lactones; D011108:Polymers; D011092:Polyethylene Glycols; C121056:caprolactone; C000595213:polyethylene glycol 400; D003022:Clotrimazole
keywords: antifungal release; clotrimazole; co-extruded fiber; poly(caprolactone)