Efficacy of nanoemulsion with Pterodon emarginatus Vogel oleoresin for topical treatment of cutaneous leishmaniasis.

Abstract

Cutaneous leishmaniasis (CL) is a neglected tropical skin disease caused by the protozoan genus Leishmania. The

treatment is restricted to a handful number of drugs that exhibit toxic effects, limited efficacy, and drug resis- tance. Additionally, developing an effective topical treatment is still an enormous unmet medical challenge.

Natural oils, e.g. the oleoresin from P. emarginatus fruits (SO), contain various bioactive molecules, especially terpenoid compounds such as diterpenes and sesquiterpenes. However, its use in topical formulations can be impaired due to the natural barrier of the skin for low water solubility compounds. Nanoemulsions (NE) are drug delivery systems able to increase penetration of lipophilic compounds throughout the skin, improving their topical effect. In this context, we propose the use of SO-containing NE (SO-NE) for CL treatment. The SO-NE was produced by a low energy method and presented suitable physicochemical characteristic: average diameter and polydispersity index lower than 180 nm and 0.2, respectively. Leishmania (Leishmania) amazonensis-infected

BALB/c mice were given topical doses of SO or SO-NE. The topical use of a combination of SO-NE and intra- peritoneal meglumine antimoniate reduced lesion size by 41 % and tissue regeneration was proven by histo- pathological analyses. In addition, a reduction in the parasitic load and decreased in the level of IFN-γ in the

lesion may be associated, as well as a lower level of the cytokine IL-10 may be associated with a less intense inflammatory process. The present study suggests that SO-NE in combination meglumine antimoniate represents a promising alternative for the topical treatment of CL caused by L. (L.) amazonensis.