Effectiveness of liposomal buparvaquone in an experimental hamster model of Leishmania (L.) infantum chagasi

Author(s)

Reimao, Juliana Q. ^[1] ; Colombo, Fabio A. ^[1] ; Pereira-Chioccola, Vera L. ^[1] ; Tempone, Andre G. ^[1]

Affiliation

^[1] Inst Adolfo Lutz Registro, Dept Parasitol, BR-01246902 Sao Paulo - Brazil

• Document type: Journal article
• Source: Experimental Parasitology; v. 130, n. 3, p. 195-199, MAR 2012.
• Web of Science Citations: 26

Abstract

The objective of this study was to develop a novel liposomal formulation, containing phosphatidylserine (PS), of buparvaquone (BPQ) and to evaluate its in vivo effectiveness in Leishmania (L.) infantum chagasi-infected hamsters. The activity of BPQ was evaluated against both the promastigote forms of different Leishmania species and the intracellular amastigotes of L. (L.) infantum chagasi. Buparvaquone was entrapped in PS-liposomes (BPQ-PS-LP), and the drug was quantified by ultra-high-performance liquid chromatography. The treatment was quantified by detecting the RNA of the living amastigotes in the spleen and the liver by real-time PCR. In vitro assays with L. (L.) infantum chagasi intracellular amastigotes were performed in peritoneal macrophages for the evaluation of the 50% inhibitory concentration (IC50). BPQ-PS-LP at 0.33 mg/kg/day for eight consecutive days reduced the number of amastigotes by 89.4% (P < 0.05) in the spleen and by 67.2% (P > 0.05) in the liver, compared to 84.3% (P < 0.05) and 99.7% (P < 0.05), respectively, following Glucantime (R) treatment at 50 mg/kg/day. Free BPQ at 20 mg/kg/day failed to treat the hamsters when compared to the untreated group. BPQ was significantly (P < 0.05) selective against L. (L.) infantum chagasi intracellular amastigotes, with an IC50 value of 1.5 mu M; no in vitro mammalian cytotoxicity could be detected. Other cutaneous species were also susceptible to BPQ with IC50 values in the range 1-4 mu M. BPQ-PS-LP caused a significant reduction in the parasite burden at a 60-fold lower dose than did the free BPQ. These results show the potential of PS-liposome formulations for the successful targeted delivery of BPQ in visceral leishmaniasis. (C) 2012 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 08/11434-3 - Therapeutic combinations in Visceral Leishmaniasis: the antileishmanial potential of calcium channel blockers
• Grantee: Juliana Quero Reimão Dalla Zanna
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 08/09260-7 - Therapeutic combinations for visceral leishmaniasis: the antileishmanial potential of calcium channel blockers and the use of liposomal nanoformulations
• Grantee: André Gustavo Tempone Cardoso
• Support type: Regular Research Grants