Enhancing the nail permeability of topically applied drugs

The topical therapy of nail diseases, especially of onychomycosis, and to a smaller extent, of nail psoriasis, is desirable to avoid the side effects associated with their systemic therapy, to increase patient compliance and reduce the cost of treatment. Systemic therapy is however the mainstay of treatment due to the poor permeability of the nail plate to topically applied drugs. For effective topical therapy, ungual drug permeation must be enhanced. This can be achieved by disrupting the nail plate using physical techniques or chemical agents. Alternatively, drug permeation into the intact nail plate may be encouraged, for example, by iontophoresis or by formulating the drug within a vehicle which enables high drug partition out of the vehicle and into the nail plate. The physical techniques (manual and electrical nail abrasion, acid etching, ablation by lasers, microporation, application of low-frequency ultrasound and electric currents) and chemicals (thiols, sulphites, hydrogen peroxide, urea, water, enzymes) that have shown ungual enhancer activity are discussed in this review. Optimal drug formulation, while crucial to ungual drug delivery, is only briefly reviewed due to the limited literature.