Artificial biomembranes for development of a drug permeation model for onychomycosis

Onychomycosis is a fungal infection of the nails caused by dermatophytes, non-dermatophytes, molds and yeasts. Several oral and external conventional therapies are currently available for treatment of the disease. However, the cure rate is low and the relapse rate is very high. Research and development of new external therapies are hampered by limited sources of human nail plates for studying drug permeation. Today, most studies are based on a bovine hooves model. However, data obtained from this model cannot always be applied to human nails, since the human nail and hoof keratin do not have an identical amino acid composition. The differences in amino acid compositions affect the 3D structure of the keratin matrix. This results in different penetration and permeation of drugs through nail plates and hooves. The present study was therefore aimed to develop a nail plate model based on keratin membranes produced from regenerated human hair keratin. Two solution compositions were tested for extraction of keratin from human hair: one is based on β-mercaptoethanol and the other on 1,4-dithiothreitol. Since the extraction rate in the latter case was higher (2.77 mg of protein h^-1 ml^-1) than in the former (1.84 mg of protein h^-1 ml^-1), the membranes were prepared using the more effective composition. The obtained membranes, human nails and bovine hoof samples were analyzed using XRD, FTIR and TGA. The results showed better similarity in functional groups and in structure between the prepared membranes and nails, than between the membranes and bovine hooves. Preliminary results demonstrated that the produced keratin membranes can be used for the development of a more accurate model for drug penetration and permeation through nail plates.