title: Trans-ungual Delivery of AR-12, a Novel Antifungal Drug.
abstract: AR-12 is a novel small molecule with broad spectrum antifungal activity. Recently, AR-12 was found to be highly active against Trichophyton rubrum, one of the predominantly responsible organisms that cause onychomycosis. The primary objective of this project was to investigate the ability of AR-12 to penetrate into and across the human nail plate followed by improving its trans-ungual permeation using different penetration enhancers. TranScreen-N™, a high throughput screening method was utilized to explore the potential nail penetration enhancers to facilitate the drug delivery through the nail. This screen demonstrated that dexpanthenol and PEG 400 were the most efficient enhancers. The in vitro permeation studies were performed across the human cadaver nail plates for 7 days with three AR-12 (5% w/v) formulations containing 10% w/v dexpanthenol (Formulation A), 10% w/v PEG 400 (Formulation B), and a combination of 10% w/v dexpanthenol + 10% w/v PEG 400 (Formulation C). The in vitro studies concluded that dexpanthenol and PEG 400 were able to deliver a significant amount of AR-12 into and across the nail plate that was found to be more than MIC 50 level of the drug.
authors.affiliation: The University of Mississippi, School of Pharmacy, University, Mississippi, USA.
authors.forename: Avadhesh Singh
authors.initials: AS
authors.lastname: Kushwaha
authors.affiliation: The University of Mississippi, School of Pharmacy, University, Mississippi, USA.
authors.forename: P
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Institute for Drug Delivery and Biomedical Research, Bangalore, India.
authors.forename: H N
authors.initials: HN
authors.lastname: Shivakumar
authors.affiliation: Ohio State University, Columbus, Ohio, USA.
authors.forename: C
authors.initials: C
authors.lastname: Rappleye
authors.affiliation: Arno Therapeutics, Flemington, New Jersey, USA.
authors.forename: A
authors.initials: A
authors.lastname: Zukiwski
authors.affiliation: Arno Therapeutics, Flemington, New Jersey, USA.
authors.forename: S
authors.initials: S
authors.lastname: Proniuk
authors.affiliation: The University of Mississippi, School of Pharmacy, University, Mississippi, USA. murthy@olemiss.edu.
authors.forename: S Narasimha
authors.initials: SN
authors.lastname: Murthy
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D009262:Nails / Q000187:drug effects* / Q000378:metabolism; D014009:Onychomycosis / Q000188:drug therapy; D011092:Polyethylene Glycols / Q000737:chemistry; D011720:Pyrazoles / Q000008:administration & dosage*; D013449:Sulfonamides / Q000008:administration & dosage*
chemical_list: D000935:Antifungal Agents; C500894:OSU 03012; D011720:Pyrazoles; D013449:Sulfonamides; D011092:Polyethylene Glycols; C000595213:polyethylene glycol 400
keywords: AR-12; TranScreen-N™; Trichophyton rubrum; onychomycosis; ungual and trans-ungual drug delivery