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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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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]
Número total de Autores: 5
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
Número total de Afiliações: 4
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