Strategies for the enhancement of nail plate permeation of drugs to treat onychomycosis

Onychomycosis is caused by dermatophytes, non-dermatophytes and yeasts. It has a global prevalence of 5.5%, requires long treatment periods, and has high relapse rates following therapy. Oral antifungals are generally the most common treatment. While effective, they have limitations such as drug-drug interactions, hepatotoxicity and adverse side effects; thus, they cannot be used in several populations. Topical antifungals do not have the safety limitations but are typically not as effective. The primary challenge of topical treatment is the permeation of drug molecules across the nail plate barrier, which is a highly cross-linked keratin network. The use of drugs and formulations with favourable characteristics such as small size, absence of lipophilicity, hydrophilic nature, hydrating properties and appropriate pH can greatly improve permeation. Here, we review physical, nanoparticle-based, formulation-based, mechanical and chemical drug delivery strategies to improve the permeation of drugs across the nail plate.