Optimization of nail therapies: the role of microstructure in the absorption and efficacy of topical treatments

The most frequent nail diseases are onychomycosis and nail psoriasis. These pathologies must be treated pharmacologically over extended periods, with topical therapy being the most desirable option to avoid the side effects linked to systemic administration. However, the low permeation of drugs applied topically to the nail plate limits the effectiveness of these treatments. The nail is a highly keratinized structure attached to the skin with essential protective and mechanical functions, but its composition, nature, and compact, dense structure limit the permeability of topically applied substances. This article analyzes the factors that affect the diffusion of active ingredients in the nail, including its structural composition, the influence of hydration and the impact of various auxiliary substances and agents that help in nail permeation. This review includes a description of the microstructural alterations caused by diseases such as onychomycosis and psoriasis, which can change nail permeability affecting the efficacy of topical treatments. It also reviews strategies to improve drug penetration, highlighting the use of hydromiscible vehicles based on cyclodextrin polypseudorataxanes or hydroxypropyl chitosan, and the use of chemical promoters such as sodium lauryl sulfate. Finally, advances in nail lacquer formulations are discussed, including those based on hydroxypropyl chitosan and cyclodextrin pseudopolyrotaxanes, which have been shown to improve the absorption and efficacy of topical antifungal treatments and therapies for nail disorders. These innovative approaches offer new perspectives for the treatment of nail diseases, facilitating the development of more effective formulations.