title: Effectiveness of liposomal buparvaquone in an experimental hamster model of Leishmania (L.) infantum chagasi.
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 (IC(50)). 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® 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 IC(50) value of 1.5 μM; no in vitro mammalian cytotoxicity could be detected. Other cutaneous species were also susceptible to BPQ, with IC(50) values in the range 1-4 μM. 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.
authors.affiliation: Department of Parasitology, Instituto Adolfo Lutz, Avenida Dr. Arnaldo, 351, 8° Andar. Cerqueira César, CEP 01246-902 São Paulo, SP, Brazil.
authors.forename: Juliana Q
authors.initials: JQ
authors.lastname: Reimão
authors.forename: Fábio A
authors.initials: FA
authors.lastname: Colombo
authors.forename: Vera L
authors.initials: VL
authors.lastname: Pereira-Chioccola
authors.forename: André G
authors.initials: AG
authors.lastname: Tempone
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D004195:Disease Models, Animal; D006801:Humans; D020128:Inhibitory Concentration 50; D018314:Leishmania infantum / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008081:Liposomes; D008253:Macaca mulatta; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000469:parasitology; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D009285:Naphthoquinones / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D010718:Phosphatidylserines
chemical_list: D000981:Antiprotozoal Agents; D008081:Liposomes; D009285:Naphthoquinones; D010718:Phosphatidylserines; C046326:buparvaquone