Department of Parasitology, Instituto Adolfo Lutz, Avenida Dr. Arnaldo, 351, 8° Andar. Cerqueira César, CEP 01246-902 São Paulo, SP, Brazil.
Exp Parasitol. 2012 Mar;130(3):195-9. doi: 10.1016/j.exppara.2012.01.010. Epub 2012 Jan 20.
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.
本研究旨在开发一种新型脂质体制剂，其中包含磷脂酰丝氨酸（PS）包裹的双羟萘酸喹啉（BPQ），并评估其在感染恰加斯利什曼原虫（L.）婴儿的仓鼠体内的有效性。BPQ 的活性针对不同利什曼原虫种的前鞭毛体形式和 L.（L.）婴儿体内的内阿米巴阶段进行了评估。将 BPQ 包封在 PS 脂质体（BPQ-PS-LP）中，并通过超高效液相色谱法定量药物。通过实时 PCR 检测脾脏和肝脏中活的内阿米巴体的 RNA 来定量治疗。在腹膜巨噬细胞中进行针对 L.（L.）婴儿内阿米巴体的体外试验，以评估 50%抑制浓度（IC（50））。BPQ-PS-LP 在连续 8 天每天 0.33 mg/kg 时，与 Glucantime® 治疗（50 mg/kg/天）相比，脾脏中的内阿米巴数量减少了 89.4%（P<0.05），肝脏中的内阿米巴数量减少了 67.2%（P>0.05）。相比之下，自由 BPQ 在 20 mg/kg/天时未能治疗仓鼠，与未治疗组相比。BPQ 对 L.（L.）婴儿内阿米巴体具有显著的选择性（P<0.05），IC（50）值为 1.5 μM；未检测到体外哺乳动物细胞毒性。其他皮肤种也容易受到 BPQ 的影响，IC（50）值在 1-4 μM 范围内。BPQ-PS-LP 在 60 倍低剂量下即可显著降低寄生虫负担，优于自由 BPQ。这些结果表明 PS 脂质体制剂具有成功靶向传递 BPQ 用于内脏利什曼病的潜力。
