In vitro and in vivo activity of a lipid-based artemisinin formulation against Leishmania (Leishmania) amazonensis

Abstract

Previous studies have demonstrated the antileishmanial potentialities of endoperoxide (EP) compounds, including artemisinin (ART). In the design of pharmaceutical formulations, the lipid-based delivery systems based on cochleates has attracted attention due to their stability, versatility, biocompatibility and biodegradability. The aim of the present study was to compare the in vitro and in vivo antileishmanial activity of ART with their nanocochleates formulations (ART-C) and reference drug Glucantime®. The antileishmanial and cytotoxic activities were evaluated on intracellular amastigotes of Leishmania (Leishmania) amazonensis and peritoneal macrophages from BALB/c mice, respectively. In vivo assessment was also performed on cutaneous leishmaniasis induced in BALB/c mice using a treatment protocol of 5 doses at 30 mg/kg every 4 days by intralesional route. The ART-C maintained its in vitro activity with an IC₅₀ of 16.3 ± 3.6 μM, which was similar to ART (14.9 ± 2.4 μM). In both cases, no cytotoxicity on peritoneal macrophages was observed at maximum concentration tested (170 μM). In ART-C treated mice, the disease development was prevented (p < 0.05) with respect to animals treated with empty cochleates (EC), treated with ART, and untreated mice, under enhanced of IL-12 formation. Our results demonstrate the benefit of ART-C as a promising antileishmanial therapeutic formulation.