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

• Published in: Experimental parasitology 2012-03, Vol.130 (3), p.195-199
• Main Authors: Reimão, Juliana Q., Colombo, Fábio A., Pereira-Chioccola, Vera L., Tempone, André G.
• Format: Article
• Language: English
• Subjects: amastigotes; animal models; Animals; Antiprotozoal Agents - administration & dosage; Antiprotozoal Agents - pharmacology; Antiprotozoal Agents - therapeutic use; Buparvaquone; Cell Line; Cells, Cultured; Cricetinae; cytotoxicity; Disease Models, Animal; drugs; hamsters; Humans; in vitro studies; Inhibitory Concentration 50; Leishmania (L.) infantum chagasi; Leishmania infantum; Leishmania infantum - drug effects; Leishmaniasis; Leishmaniasis, Visceral - drug therapy; Liposomes; liver; Macaca mulatta; macrophages; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - parasitology; Male; Mesocricetus; Mice; Mice, Inbred BALB C; Naphthoquinones - administration & dosage; Naphthoquinones - pharmacology; Naphthoquinones - therapeutic use; parasites; parasitology; Phosphatidylserines; quantitative polymerase chain reaction; RNA; spleen; Therapy; ultra-performance liquid chromatography; visceral leishmaniasis
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2012.01.010

[Display omitted] ► Leishmania infantum-infected hamsters were treated i.p. with liposomal buparvaquone at 0.33mg/kg/day for eight consecutive days. ► This treatment reduced the parasite burden by 89% in the spleen and 67% in the liver. ► Buparvaquone showed a high in vitro selectivity index against Leishmania amastigotes. 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 0.33mg/kg/day for eight consecutive days reduced the number of amastigotes by 89.4% (P0.05) in the liver, compared to 84.3% (P