Pharmacokinetic of meglumine antimoniate encapsulated in phosphatidylserine-liposomes in mice model: A candidate formulation for visceral leishmaniasis

Autor(es)

Treiger Borborema, Samanta Etel ^{[1, 2]} ; Osso Junior, Joao Alberto ^[3] ; Tempone, Andre Gustavo ^[2] ; de Andrade Junior, Heitor Franco ^[4] ; do Nascimento, Nanci ^[1]

Afiliação do(s) autor(es)

^[1] Inst Pesquisas Energet & Nucl CNEN SP, Ctr Biotecnol, Av Lineu Prestes 2242, BR-05508000 Sao Paulo, SP - Brazil

^[2] Adolfo Lutz Inst, Ctr Parasitol & Micol, Av Dr Arnaldo 351, 8 Andar, BR-01246000 Sao Paulo, SP - Brazil

^[3] Inst Pesquisas Energet & Nucl CNEN SP, Ctr Radiofarm, Av Lineu Prestes 2242, BR-05508000 Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, FMUSP, Inst Med Trop Sao Paulo, Lab Protozool, Av Dr Eneas de Carvalho Aguiar 470, 1 Andar, BR-05403000 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOMEDICINE & PHARMACOTHERAPY; v. 103, p. 1609-1616, JUL 2018.
• Citações Web of Science: 2

Resumo

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. (AU)

• Processo FAPESP: 14/24908-4 - Avaliação da atividade antileishmania de fármacos anti-histamínicos e identificação de alterações celulares relacionadas à resposta terapêutica em Leishmania (Leishmania) infantum
• Beneficiário: Viviane de Melo Mendes
• Linha de fomento: Bolsas no Brasil - Iniciação Científica