Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 103, Issue -, Pages 1609-1616Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2018.05.004
Keywords
Leishmaniasis; Liposome; Pentavalent antimony; Pharmacokinetic; Phosphatidylserine; Radiolabeling
Funding
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [142839/2005-1, 201308/2008-8, 457099/2014-3]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2014/24908-4]
- [LIM-49-HC-FMUSP]
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Visceral leishmaniasis (VL) is a fatal parasitic disease caused by the protozoan Leishmania spp. Meglumine antimoniate (MA) is the main treatment and has demonstrated a promising efficacy in a VL-model when encapsulated into negatively charged liposomes. Considering the current concept for the evaluation of pharmacokinetic parameters at early phases of drug discovery, we developed a formulation of MA-encapsulated into phosphatidylserine liposomes (MA-LP) and analyzed the in vitro antileishmanial activity, physicochemical properties, and pharmacokinetic profile in a mice model. The liposomal formulation had an internal mean diameter of 114 nm and a high stability in plasma. MA-LP was 23-fold more in vitro effective against Leishmania infantum-infected macrophages than the free drug, with a selectivity index higher than 220. The pharmacokinetic studies demonstrated that the liposomes increased the uptake of the drug by the liver and spleen and promoted sustained levels. MA-LP was first eliminated through renal excretion, followed by biliary excretion. In the blood, MA-LP followed a biexponential open model. This work emphasizes the importance of liposomes as potential drug delivery systems for visceral leishmaniasis.
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