Bioadhesive patch-based delivery of 5-aminolevulinic acid to the nail for photodynamic therapy of onychomycosis

The in vitro penetration of 5-aminolevulinic acid (ALA) across human nail and into neonate porcine hoof when released from a novel bioadhesive patch containing 50 mg cm−2 ALA is described. ALA is a naturally occurring precursor of the photosensitiser protoporphyrin IX (PpIX). Topical application of excess ALA bypasses negative feedback inhibition and yields photosensitising concentrations of PpIX at the application site. ALA-based photodynamic therapy (PDT) has been extensively investigated in the topical treatment of various skin neoplasias. Recently, its use has been extended to the microbiological field. If sufficient concentrations of ALA could be achieved within the nail matrix, and at the nail bed, PDT may prove to be a useful treatment for onychomycosis. Patch application for 24 h allowed an ALA concentration of 2.8 mM to be achieved on the ventral side of excised human nail. Application for 48 h induced a concentration of 6.9 mM. Application time had no significant effect on the ALA concentration at mean depths of 2.375 mm in neonate porcine, with application times of 24, 48 and 72 h all producing concentrations of 0.1 mM. Incubation of Candida albicans and Trichophyton interdigitale with ALA concentrations of 10.0 mM for 30 min and 6 h, respectively, caused reductions in viability of 87% and 42%, respectively, following irradiation with red light. Incubation with 0.1 mM ALA for 30 min and 6 h, respectively, caused reductions in viability of 32% for Candida albicans and 6% for Trichophyton interdigitale, following irradiation. Drug penetration across nail may be improved using penetration enhancers, or by filing of the impenetrable dorsal surface of the nail. Moreover, iron chelators can be used to increase PpIX production for a given ALA dose. Therefore, with suitable modifications, ALA-PDT may prove to be a viable alternative in the treatment of onychomycosis.