Fundação Oswaldo Cruz (FIOCRUZ-RONDÔNIA), Porto Velho, RO, Brazil.
Exp Parasitol. 2013 Oct;135(2):337-43. doi: 10.1016/j.exppara.2013.07.022. Epub 2013 Aug 6.
Leishmania amazonensis causes human diseases that range from self-healing to diffusion cutaneous lesions. The chemotherapy of leishmaniasis requires long-term treatment and has been based on the use of pentavalent antimonials. Liposomes have been used as antileishmanial drug carries and have adjuvant activity in vaccines against several microorganisms, representing an important option to the development of new therapeutics for the disease. In this study, we developed a liposomal formulation containing lupane [3β,6β,16β-trihydroxylup-20(29)-ene], isolated from fruits of Combretum leprosum with pharmacological properties as antinociceptive, anti-inflammatory, antiulcerogenic and antileishmanial activities. The aim of the present study was to evaluate the efficacy of liposomal-lupane in L. amazonensis-infection model. Liposomes were prepared by the extrusion method with DPPC, DPPS and cholesterol at 5:1:4 weight ratio. The lupane (2 mg/mL) was added to the lipid mixture, solubilized in chloroform and dried under nitrogen flow. The activity of liposomal-lupane was conducted in vitro with mouse peritoneal infected macrophages. Furthermore, mice were infected in the right hind footpad with 10(5) stationary growth phase of L. amazonensis promastigotes. After 6 weeks, animals were treated with liposomal-lupane for 15 days by intraperitoneal injection. The evolution of disease was monitored weekly by measuring footpad thickness with a caliper. Three days after the treatment, peritoneal macrophages were collected, plated and production of the cytokines IL-10 and IL-12 was evaluated in supernatants of the cultures after 24 h. The results indicate that the liposomal system containing lupane achieved here is a promising tool to confer antileishmanial activity to infected macrophages.
亚马逊利什曼原虫可引起从自限性到皮肤扩散性损害等多种人类疾病。利什曼病的化学疗法需要长期治疗，并且一直基于使用五价锑。脂质体已被用作抗利什曼原虫药物载体，并在针对几种微生物的疫苗中具有佐剂活性，这是开发该疾病新疗法的重要选择。在这项研究中，我们开发了一种含有羽扇豆烷[3β,6β,16β-三羟基羽扇-20(29)-烯]的脂质体制剂，该羽扇豆烷从麻风树果实中分离得到，具有镇痛、抗炎、抗溃疡和抗利什曼原虫活性。本研究旨在评估脂质体-羽扇豆烷在 L. amazonensis 感染模型中的疗效。脂质体通过挤压法制备，DPPC、DPPS 和胆固醇的重量比为 5:1:4。将羽扇豆烷（2 mg/mL）加入脂质混合物中，溶于氯仿中并在氮气流下干燥。在体外使用感染有鼠腹膜巨噬细胞的 L. amazonensis 进行了脂质体-羽扇豆烷的活性检测。此外，将 10(5)个静止生长期的 L. amazonensis 前鞭毛体感染于小鼠右后脚掌垫。6 周后，通过腹腔注射用脂质体-羽扇豆烷治疗 15 天。每周通过卡尺测量足垫厚度来监测疾病的进展。治疗后 3 天，收集腹膜巨噬细胞，接种并在培养物上清液中培养 24 h 后评估细胞因子 IL-10 和 IL-12 的产生。结果表明，此处获得的含有羽扇豆烷的脂质体制剂是赋予感染巨噬细胞抗利什曼原虫活性的有前途的工具。
