Artigo de peri??dico
Pharmacokinetic of meglumine antimoniate encapsulated in phosphatidylserine-liposomes in mice model
Registro en:
0753-3322
103
10.1016/j.biopha.2018.05.004
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Autor
BORBOREMA, SAMANTA E.T.
OSSO JUNIOR, JOAO A.
TEMPONE, ANDRE G.
ANDRADE JUNIOR, HEITOR F. de
NASCIMENTO, NANCI do
Resumen
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. Conselho Nacional de Desenvolvimento Cient??fico e Tecnol??gico (CNPq) Funda????o de Amparo ?? Pesquisa do Estado de S??o Paulo (FAPESP) CNPq: 142839/2005-1; 201308/2008-8; 457099/2014-3 FAPESP: 14/24908-4