Advances in leishmaniasis therapy: preparation, characterization and <i>in vitro</i> evaluation of poly (lactic acid) polymeric nanoparticles with the drug candidate SB-83

Leishmaniasis, a vector-borne disease transmitted by phlebotomine sandflies and caused by protozoa of the genus Leishmania, constitutes a significant public health challenge, with approximately one million new cases reported annually. Current therapeutic options are constrained by issues related to toxicity, suboptimal efficacy, and elevated costs. This study details the formulation, lyophilization, physicochemical characterization, and in vitro assessment of poly(lactic acid) (PLA) nanoparticles encapsulating SB-83, a novel antileishmanial compound, with the aim of enhancing its therapeutic profile. The nanoparticles were prepared via the nanoprecipitation method, yielding spherical particles with mean diameters ranging from 146,4 to 239 nm. The lyophilization process was capable to obtain NPs with excellent stability and particle recovery and shows influence in SB-83 delivery. Encapsulation efficiency varied between 65% and 86%, contingent upon the specific preparation method. A sustained release of SB-83 from the nanoparticles was observed over a period of up to 96 hours. In vitro analyses confirmed the efficacy of SB-83-loaded nanoparticles against both promastigote and amastigote forms of Leishmania (L.) amazonensis, demonstrating a substantial increase in the selectivity index to 50% and a reduction in cytotoxicity toward macrophages by more than 85%. Collectively, these findings indicate that PLA nanoparticles loaded with SB-83 offer a promising drug delivery platform for the treatment of leishmaniasis, providing prolonged release, enhanced efficacy and selectivity against the parasite, and decreased adverse effects. These results underscore the potential of nanoparticle-based systems as innovative and effective therapeutic strategies for leishmaniasis.