Comparative Ungual Drug Uptake Studies: Equine Hoof Membrane vs. Human Nail Plate

Abstract

Human nail diseases, mostly caused by fungal infections, are common and difficult to treat. The development and testing of new drugs and drug delivery systems for the treatment of nail diseases is often limited by the lack of human nail material for permeation studies. Animal material is frequently used, but there are only few comparative data on the human nail plate, and there is neither a standardized test design nor a nail bed analogue to study drug uptake into the nail. In this study, a new permeation device was developed for permeation studies, and the permeation behavior of three model substances on the human nail plate and a model membrane from the horse hoof was investigated. A linear correlation was found between drug uptake by the human nail plate and the uptake by the equine hoof. The developed and established permeation device is suitable for investigations of ungual drug transport and enables the use of different membrane diameters and the use of a gel-based nail bed analog. The hydrogel-based acceptor medium used ensures adequate stabilization and hydration of the nail membrane.

Keywords: caffeine; equine hoof membrane; human nail plate; permeation device; sorbic acid; testosterone; ungual penetration; ungual permeation.

Figure 1

Two-chamber permeation device. Individual components (a), assembled permeation gadget top view with Teflon adapter (b), closed permeation device (c).

Figure 2

Water content of the hoof membrane over 120 h, depending on the incubation medium, water (ο) or gel (□), obtained by gravimetric measurements. Mean value ± standard deviation, n = 6.

Figure 3

Results of the drug (a) permeation through and (b) penetration into nail (grey) and hoof (white) membrane after 24 h of exposure to caffeine, sorbic acid, and testosterone (donor: 20 µg). Box plot with median, minimum, maximum, and the 0.25 and 0.75 quartiles. n = 6.

Figure 4

Results of the drug (a) permeation through and (b) penetration into nail (grey) and hoof (white) membrane after 24 h of exposure to caffeine and sorbic acid (donor: 100 µg). Box plot with median, minimum, maximum, and the 0.25 and 0.75 quartiles, n = 6.

Figure 5

Results of the drug (a) permeation through and (b) penetration into nail (grey) and hoof (white) membrane after 120 h of exposure to caffeine, sorbic acid, and testosterone (donor: 20 µg). Box plot with median, minimum, maximum, and the 0.25 and 0.75 quartiles, n = 6.

Figure 6

Correlation between human nail and equine hoof membranes in terms of (top) the penetrated (R²: 0.985), (middle) the permeated (R²: 0.616), and (bottom) the total drug uptake (R²: 0.986) drug amount, considering the experimental time and the applied drug amount: ○ caffeine, ☐ sorbic acid, and △ testosterone. Mean value ± standard deviation, n = 6.