In-vitro Permeability of the Human Nail and of a Keratin Membrane from Bovine Hooves: Influence of the Partition Coefficient Octanol/Water and the Water Solubility of Drugs on their Permeability and Maximum Flux

Abstract

Penetration of homologous nicotinic acid esters through the human nail and a keratin membrane from bovine hooves was investigated by modified Franz diffusion cells in-vitro to study the transport mechanism. The partition coefficient octanol/water PCOct/W of the esters was over the range 7 to > 51,000. The permeability coefficient P of the nail plate as well as the hoof membrane did not increase with increasing partition coefficient or lipophilicity of the penetrating substance. This indicates that both barriers behave like hydrophilic gel membranes rather than lipophilic partition membranes as in the case of the stratum corneum. Penetration studies with the model compounds paracetamol and phenacetin showed that the maximum flux was first a function of the drug solubility in water or in the swollen keratin matrix. Dissociation hindered the diffusion of benzoic acid and pyridine through the hoof membrane. Since keratin, a protein with an isoelectric point of about 5, is also charged, this reduction can be attributed to an exclusion of the dissociating substance due to the Donnan equilibrium. Nevertheless, the simultaneous enhancement of the water solubility makes a distinct increase of the maximum flux possible. In order to screen drugs for potential topical application to the nail plate, attention has to be paid mainly to the water solubility of the compound. The bovine hoof membrane may serve as an appropriate model for the nail.

Establishment of a Novel Model of Onychomycosis in Rabbits for Evaluation of Antifungal Agents

“…Some reports suggest that the nail has properties like those of a hydrophilic gel membrane (13,16), which prevents the penetration of the nail plate by chemicals and drugs (5). In addition, the histopathological examination of nail biopsy specimens revealed the presence of fungi near the distal and proximal nail bed in the distal subungual type (DSO) (11).…”

In vitro evaluation of the antifungal efficacy of poloxamer 407-based formulations in an infected nail plate model

“…Moreover, bovine hoof plates exhibit a more widely meshed keratin matrix and swell to a higher extent during incubation in water. Following, permeation coefficients are reported to be up to 30-fold higher in comparison to those obtained with human nails (Mertin and Lippold, 1997a;Mertin and Lippold, 1997b). Regarding the KF, Täuber and Müller-Goymann (2015) found out that permeation coefficients across KF were 1.4 -2.3 times higher than permeation coefficients across bovine hoof plates.…”

Transungual permeation: current insights

“…Animal hooves have been used as substitute to nail plate for studying transungual permeation [79][80][81]. There is a close structural similarity between bovine hoof and human nail plate [82,83]. Bovine hooves are a validated model substitute to nail plate for studying transungual permeation and in vitro efficacy study [84].…”