Nanoparticles as multifunctional devices for the topical treatment of cutaneous leishmaniasis

Cutaneous and mucocutaneous leishmaniasis are major tropical skin diseases. Topical treatment is currently limited to the least severe forms of cutaneous leishmaniasis (CL) without risk of dissemination. It is also recommended in combination with systemic therapy for more severe forms. Progresses in this modality of treatment are hindered by the heterogeneity of the disease and shortcomings in the clinical trials.

This review overlooks three major modalities of topical therapies in use or under investigation against CL: chemotherapy, photodynamic therapy and immunotherapy; either with older compounds such as paramomycin or more recent nitric oxide donors, antimicrobial peptides or silver derivatives. The advantages and limitations of their administration with newer formulation strategies such as nanoparticles (NPs) are discussed.

The efficacy of a topical treatment against CL depends not only on the intrinsic antileishmanial activity of the drug but also on the amount of drug available in the dermis. NPs as sustained release systems and permeation enhancers could favour the creation of a drug reservoir in the dermis. Additionally, certain NPs have immunomodulatory properties or wound healing capabilities of benefit in CL treatment. Pending task is the selective delivery of active compounds to intracellular amastigotes, because even small NPs are unable to penetrate deeply into the skin to encounter infected macrophages (except in ulcerative lesions).