title: Controlled nail delivery of a novel lipophilic antifungal agent using various modern drug carrier systems as well as in vitro and ex vivo model systems.
abstract: The penetration behavior into human nails and animal hoof membranes of a novel antifungal agent (EV-086K) for the treatment of onychomycosis was investigated in this study. The new drug provides a high lipophilicity which is adverse for penetration into nails. Therefore, four different formulations were developed, with particular focus on a colloidal carrier system (CCS) due to its penetration enhancing properties. On the one hand, ex vivo penetration experiments on human nails were performed. Afterwards the human nail plates were cut by cryomicrotome in order to quantify the drug concentration in the dorsal, intermediate and ventral nail layer using high-performance liquid chromatography (HPLC) with UV detection. On the other hand, equine and bovine hoof membranes were used to determine the in vitro penetration of the drug into the acceptor compartment of an online diffusion cell coupled with Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy. In combination, both results should exhibit a correlation between the EV-086K penetration behavior in human nail plates and animal hoof membranes. The investigations showed that the developed CCS could increase drug delivery through the human nail most compared to other formulations (nail lacquer, solution and hydrogel). Using animal hooves in the online diffusion cell, we were able to calculate pharmacokinetic data of the penetration process, especially diffusion and permeability coefficients. Finally, a qualitative correlation between the penetration results of human nails and equine hooves was established.
authors.affiliation: Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Halle (Saale) Germany. Electronic address: sandy.naumann@pharmazie.uni-halle.de.
authors.forename: Sandy
authors.initials: S
authors.lastname: Naumann
authors.affiliation: Evolva Holding SA, Reinach, Switzerland.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Meyer
authors.affiliation: Fraunhofer Institute for Mechanics of Materials IWM, Halle (Saale), Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kiesow
authors.affiliation: Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Halle (Saale) Germany.
authors.forename: Yahya
authors.initials: Y
authors.lastname: Mrestani
authors.affiliation: Department of Dermatology and Venereology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Wohlrab
authors.affiliation: Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Halle (Saale) Germany. Electronic address: reinhard.neubert@pharmazie.uni-halle.de.
authors.forename: Reinhard H H
authors.initials: RH
authors.lastname: Neubert
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002417:Cattle; D003102:Colloids / Q000737:chemistry / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D006724:Hoof and Claw / Q000378:metabolism; D006736:Horses; D006801:Humans; D009262:Nails / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D003102:Colloids; D003692:Delayed-Action Preparations; D004337:Drug Carriers
keywords: Antifungal; Colloidal drug carrier system; FTIR-ATR spectroscopy; Human nail; Model membranes; Nail penetration