Parasite Immunology Laboratory, Department of Biotechnology, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
Department of Medical Laboratories Technology, Faculty of Applied Medical Sciences, Taibah University, P.O. Box 344, Universities Road, Medina 30001, Saudi Arabia.
Colloids Surf B Biointerfaces. 2015 Jun 1;130:215-21. doi: 10.1016/j.colsurfb.2015.04.013. Epub 2015 Apr 18.
Visceral leishmaniasis (VL) is a fatal vector-borne parasitic syndrome attributable to the protozoa of the Leishmania donovani complex. The available chemotherapeutic options are not ideal due to their potential toxicity, high cost and prolonged treatment schedule. In the present study, we conjectured the use of nano drug delivery systems for plant-derived secondary metabolite; artemisinin as an alternative strategy for the treatment of experimental VL. Artemisinin-loaded poly lactic co-glycolic acid (ALPLGA) nanoparticles prepared were spherical in shape with a particle size of 220.0±15.0 nm, 29.2±2.0% drug loading and 69.0±3.3% encapsulation efficiency. ALPLGA nanoparticles administered at doses of 10 and 20mg/kg body weight showed superior antileishmanial efficacy compared with free artemisinin in BALB/c model of VL. There was a significant reduction in hepatosplenomegaly as well as in parasite load in the liver (85.0±5.4%) and spleen (82.0±2.4%) with ALPLGA nanoparticles treatment at 20mg/kg body weight compared to free artemisinin (70.3±0.6% in liver and 62.7±3.7% in spleen). In addition, ALPLGA nanoparticle treatment restored the defective host immune response in mice with established VL infection. The protection was associated with a Th1-biased immune response as evident from a positive delayed-type hypersensitivity reaction, escalated IgG2a levels, augmented lymphoproliferation and enhancement in proinflammatory cytokines (IFN-γ and IL-2) with significant suppression of Th2 cytokines (IL-10 and IL-4) after in vitro recall, compared to infected control and free artemisinin treatment. In conclusion, our results advocate superior efficacy of ALPLGA nanoparticles over free artemisinin, which was coupled with restoration of suppressed cell-mediated immunity in animal models of VL.
内脏利什曼病（VL）是一种致命的虫媒寄生虫综合征，由利什曼原虫复合物的原生动物引起。由于其潜在的毒性、高成本和延长的治疗方案，现有的化学治疗选择并不理想。在本研究中，我们推测使用植物源性次级代谢产物的纳米药物递送系统；青蒿素作为治疗实验性 VL 的替代策略。制备的青蒿素负载聚乳酸-共-羟基乙酸（ALPLGA）纳米粒呈球形，粒径为 220.0±15.0nm，药物载药量为 29.2±2.0%，包封率为 69.0±3.3%。与游离青蒿素相比，ALPLGA 纳米粒在 BALB/c 型 VL 模型中以 10 和 20mg/kg 体重给药时显示出优越的抗利什曼原虫功效。与游离青蒿素（肝中 70.3±0.6%，脾中 62.7±3.7%）相比，ALPLGA 纳米粒在 20mg/kg 体重时治疗可显著减少肝脾肿大以及肝（85.0±5.4%）和脾（82.0±2.4%）中的寄生虫负荷。此外，ALPLGA 纳米粒治疗可恢复已建立 VL 感染小鼠受损的宿主免疫反应。这种保护与 Th1 偏向的免疫反应有关，如迟发型超敏反应阳性、IgG2a 水平升高、淋巴增殖增强以及促炎细胞因子（IFN-γ 和 IL-2）增强，同时 Th2 细胞因子（IL-10 和 IL-4）显著抑制，与感染对照和游离青蒿素治疗相比。总之，我们的结果表明，ALPLGA 纳米粒优于游离青蒿素，这与 VL 动物模型中受抑制的细胞介导免疫的恢复有关。
