Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK.
J Biomed Nanotechnol. 2012 Aug;8(4):695-702. doi: 10.1166/jbn.2012.1414.
Leishmaniasis is a protozoan disease, which is responsible for response for major epidemics in many parts of the World. Amphotericin B (AMB) is one of the drugs used to treat leishmaniasis but it must be given intravenously and serious side effects such as nephrotoxicity can limit its use. Development of a formulation of AMB, which can be given by a non-invasive route but is still as effective as the conventional formulation, whilst causing minimal adverse side effects, is required. The present study describes a method for scale up production of a per oral nanoparticle formulation of AMB (AMB-NP) and compared its efficacy both in vitro and in vivo against Leishmania donovavni. Prophylactic studies showed that the AMB-NP formulation was significantly more effective (p < 0.05) than the same dose of AMB solution at suppressing parasite numbers compared to controls in bone marrow derived macrophages infected with L. donovani. Per oral treatment with AMB-NP resulted in a significant reduction in liver parasite burdens (p < 0.05) compared to control values and the formulation had a similar antileishmanial activity against parasites with different inherent susceptibilities to sodium stibogluconate.
利什曼病是一种原生动物疾病，在世界许多地区都曾引发过重大疫情。两性霉素 B（AMB）是用于治疗利什曼病的药物之一，但必须静脉注射，而且其肾毒性等严重副作用可能会限制其使用。需要开发一种可通过非侵入性途径给予的 AMB 制剂，其疗效与常规制剂相当，但副作用最小。本研究描述了一种口服纳米粒 AMB（AMB-NP）制剂的放大生产方法，并比较了其在体外和体内对杜氏利什曼原虫的疗效。预防性研究表明，与对照组相比，AMB-NP 制剂在骨髓来源的巨噬细胞中感染杜氏利什曼原虫时，对寄生虫数量的抑制作用明显优于相同剂量的 AMB 溶液（p<0.05）。与对照组相比，口服 AMB-NP 治疗可显著降低肝脏寄生虫负荷（p<0.05），并且该制剂对固有对葡萄糖酸锑钠敏感性不同的寄生虫具有相似的抗利什曼活性。
