MIXED FORMULATION OF CONVENTIONAL AND PEGYLATED MEGLUMINE ANTIMONIATE-CONTAINING LIPOSOMES REDUCES INFLAMMATORY PROCESS AND PARASITE BURDEN IN L. infantum INFECTED BALB/c MICE [PublishAheadOfPrint]

Pentavalent antimonial has been the first choice treatment for visceral leishmaniasis, however, it has several side effects that leads to low adherence to treatment. Liposome-encapsulated meglumine antimoniate (MA) arises as an important strategy for chemotherapy enhancement. Herein was evaluated the immunopathological changes using the mixture of conventional and pegylated liposomes with MA. The mice were infected with L. infantum and a single dose treatment regimen. Comparison was made with groups treated with saline, empty liposomes, free MA, and liposomal formulation of MA. Histopathological analyses demonstrated that animals treated with Lipo MA, showed a significant decrease in the inflammatory process and absence of granulomas. The in vitro stimulation of splenocytes showed a significant increase of IFN--produced by CD8⁺ T-cells and a decrease of IL-10-produced by CD4⁺ and CD8⁺ T-cells in the Lipo MA. Furthermore, Lipo MA group showed an increase in the IFN-/IL-10 ratio in both CD4⁺ and CD8⁺ T-cells subsets. According to the parasite load evaluation using qPCR, Lipo MA group showed no L. infantum DNA in spleen (0.0%) and 41.4% in liver. Additionally, we detected a low positive correlation between parasitism and histopathology findings (inflammatory process and granuloma formation). Thus, our results confirmed that the Lipo MA is a promising antileishmanial formulation able to reduce the inflammatory response and induce a type 1 immune response, accompanied by a significant reduction of the parasite burden into hepatic and splenic compartment in treated animals.

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