Ex Vivo Toe Model Used to Assess Applicators for the Iontophoretic Ungual Delivery of Terbinafine

Purpose An ex vivo intact toe model was developed to assess two different applicator designs for iontophoretic delivery of terbinafine into the nail only or the nail and surrounding skin. Methods Iontophoretic permeation studies were carried out on intact cadaver toes using nail-only and nail/skin applicators with a current dose of 10 mA*min (0.5 mA for 20 min). Results Iontophoresis enhanced drug permeation and tissue loading with both applicators tested. Greater drug delivery was observed with the nail/skin applicator due to the additional terbinafine being delivered directly through the lower impedance skin area surrounding the nail. The concentration of drug loaded into the contact area of the nail with the nail-only and nail/skin applicator was ~13 and ~7 fold higher than their respective passive delivery levels but equivalent from each other in total drug mass delivered over the whole nail plate. In vitro release of drug from the iontophoretically loaded nails into agar suggests that a single treatment could have a prolonged effect (>50 days). Conclusions This study demonstrates that the ex vivo toe model was useful in assessing the functionality of the different applicator designs. These results suggest that iontophoresis can significantly enhance the delivery of drugs to both the hard and soft tissues of the toe for the treatment of onychomycosis and other nail disorders.