title: Coaxially electrospun fiber-based microbicides facilitate broadly tunable release of maraviroc.
abstract: Electrospun fibers show potential as a topical delivery system for vaginal microbicides. Previous reports have demonstrated delivery of anti-HIV and anti-STI (sexually transmitted infection) agents from fibers formulated using hydrophilic, hydrophobic, or pH-responsive polymers that result in rapid, prolonged, or stimuli-responsive release, respectively. However, coaxial electrospun fibers have yet to be evaluated as a highly tunable microbicide delivery vehicle. In this research, we explored the opportunities and limitations of a model coaxial electrospun fiber system to provide broad and tunable release rates for the HIV entry inhibitor maraviroc. Specifically, we prepared ethyl cellulose (EC)-shell and polyvinylpyrrolidone (PVP)-core fibers that were capable of releasing actives over a range of hours to several days. We further demonstrated simple and effective methods for combining core-shell fibers with rapid-release formulations to provide combined instantaneous and sustained maraviroc release. In addition, we investigated the effect of varying release media on maraviroc release from core-shell fibers, and found that release was strongly influenced by media surface tension and drug ionization. Finally, in vitro cell culture studies show that our fiber formulations were not cytotoxic and that electrospun maraviroc maintained similar antiviral activity compared to neat maraviroc.
authors.affiliation: Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, WA, 98195-5061, USA.
authors.forename: Cameron
authors.initials: C
authors.lastname: Ball
authors.affiliation: Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, WA, 98195-5061, USA.
authors.forename: Shih-Feng
authors.initials: SF
authors.lastname: Chou
authors.affiliation: Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, WA, 98195-5061, USA.
authors.forename: Yonghou
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, WA, 98195-5061, USA. Electronic address: woodrow@uw.edu.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Woodrow
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D003510:Cyclohexanes / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D000077592:Maraviroc; D008855:Microscopy, Electron, Scanning; D056951:Photoelectron Spectroscopy; D011205:Povidone / Q000737:chemistry; D013499:Surface Properties; D014230:Triazoles / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity
chemical_list: D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D003510:Cyclohexanes; D004337:Drug Carriers; D014230:Triazoles; C013517:ethyl cellulose; D002482:Cellulose; D011205:Povidone; D000077592:Maraviroc
keywords: Coaxial; Core-shell; Drug delivery; Electrospinning; Maraviroc; Microbicide