Tamargo Beatriz, Monzote Lianet, Piñón Abel, Machín Laura, García Marley, Scull Ramón, Setzer William N
Department of Pharmacology, Institute of Pharmacy and Food, Havana University, Havana 10400, Cuba.
Parasitology Department, Institute of Tropical Medicine Pedro Kouri, Havana 10400, Cuba.
Medicines (Basel). 2017 Jun 9;4(2):38. doi: 10.3390/medicines4020038.
Leishmaniasis is a zoonotic disease caused by protozoan parasites from genus. Currently, there are no effective vaccines available and the available therapies are far from ideal. In particular, the development of new therapeutic strategies to reduce the infection caused by could be considered desirable. Different plant-derived products have demonstrated antileishmanial activity, including the essential oil (EO) from L. (EO-Aa), Asteraceae. In the present study, the EO-Aa formulated in nanocochleates (EO-Aa-NC) was investigated in vitro against intracellular amastigotes of and non-infected macrophages from BALB/c mice. In addition, the EO-Aa-NC was also evaluated in vivo against on experimental cutaneous leishmaniasis, which body weight, lesion progression, and parasite load were determined. EO-Aa-NC displayed IC values of 21.5 ± 2.5 μg/mL and 27.7 ± 5.6 μg/mL against intracellular amastigotes of and non-infected peritoneal macrophage, respectively. In the animal model, the EO-Aa-NC (30 mg/kg/intralesional route/every 4 days 4 times) showed no deaths or weight loss greater than 10%. In parallel, the EO-Aa-NC suppressed the infection in the murine model by approximately 50%, which was statistically superior ( < 0.05) than controls and mice treated with EO-Aa. In comparison with Glucantime, EO-Aa-NC inhibited the progression of infection as efficiently ( > 0.05) as administration of the reference drug. Encochleation of EO-Aa resulted in a stable, tolerable, and efficacious antileishmanial formulation, facilitating systemic delivery of EO, with increased activity compared to administration of the free EO-Aa. This new formulation shows promising potential to future studies aimed at a new therapeutic strategy to treat leishmaniasis.
利什曼病是一种由利什曼原虫属原生动物寄生虫引起的人畜共患病。目前,尚无有效的疫苗,现有的治疗方法也远非理想。特别是,开发新的治疗策略以减少由[具体寄生虫名称缺失]引起的感染可能是值得期待的。不同的植物衍生产品已显示出抗利什曼原虫活性,包括来自菊科植物[植物名称缺失]的精油(EO-Aa)。在本研究中,对纳米耳蜗制剂(EO-Aa-NC)中的EO-Aa进行了体外抗[具体寄生虫名称缺失]细胞内无鞭毛体和BALB/c小鼠未感染巨噬细胞的研究。此外,还在体内对EO-Aa-NC进行了实验性皮肤利什曼病的评估,测定了体重、病变进展和寄生虫载量。EO-Aa-NC对[具体寄生虫名称缺失]细胞内无鞭毛体和未感染的腹腔巨噬细胞的IC值分别为21.5±2.5μg/mL和27.7±5.6μg/mL。在动物模型中,EO-Aa-NC(30mg/kg/病灶内给药途径/每4天1次,共4次)未出现死亡或体重减轻超过10%的情况。同时,EO-Aa-NC在小鼠模型中抑制感染约50%,在统计学上优于(P<0.05)对照组和用EO-Aa治疗的小鼠。与葡糖胺相比,EO-Aa-NC抑制感染进展的效果与参考药物给药一样有效(P>0.05)。EO-Aa的耳蜗化产生了一种稳定、可耐受且有效的抗利什曼原虫制剂,促进了EO的全身递送,与游离EO-Aa给药相比活性增加。这种新制剂在旨在治疗利什曼病的新治疗策略的未来研究中显示出有希望的潜力。