Nanoparticles in the Topical Treatment of Cutaneous Leishmaniasis: Gaps, Facts, and Perspectives

Abstract Cutaneous leishmaniasis (CL) is one of the major tropical skin diseases. It is characterized by the appearance of a papule and then a nodule that progressively ulcerates to become the characteristic lesion of the disease. Depending on the species of the parasite, CL can produce mucosal destruction, or the lesions can heal spontaneously but result in lifelong and atrophic scarring. A topical therapy that is able to shorten the duration of lesions and prevent scarring does not exist yet. Major barriers to success are the deep dermal and intracellular localization of the target, the parasite inside the dermal macrophages, and gaps in understanding of the host immune system contribution to the skin damage. Nanoparticles (NPs) have demonstrated the ability to enhance local skin accumulation of certain drugs and the efficacy of paromomycin, the standard therapy. Liposomal amphotericin B, silver NPs, nitric-oxide release systems, or encapsulated photosensitizers have also been tested with more or less success. The unraveling of the interactions between NPs and skin cells that favor the resolution of the lesions are necessary to make progress and to enable us to decide between the use of more inert NP or more proinflammatory nanomaterials. We envisage a CL topical therapy composed of an antileishmanial agent given in combination with biotechnological products designed to counteract the immunological factors responsible for tissue injury and promote wound healing. siRNA, growth factors, antisense oligonucleotides, and antibodies need the protection from degradation to be active and this can be achieved with the use of NPs.