| Full text | |
| Author(s): |
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]
Total Authors: 5
|
| Affiliation: | [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
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | BIOMEDICINE & PHARMACOTHERAPY; v. 103, p. 1609-1616, JUL 2018. |
| Web of Science Citations: | 2 |
| Abstract | |
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) | |
| FAPESP's process: | 14/24908-4 - Evaluation of antileishmanial activity of antihistaminic drugs and identification of cellular alteration related to therapeutic response in Leishmania (Leishmania) infantum |
| Grantee: | Viviane de Melo Mendes |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |