Abstract：
Alveolar echinococcosis (AE) is a severe disease caused by the infection with the larval stage of Echinococcus multilocularis, the metacestode. As there is no actual curative drug therapy, recommendations to manage AE patients are based on radical surgery and prophylactic administration of albendazole or mebendazole during 2 years to prevent relapses. There is an urgent need for new therapeutic strategies for the management of AE, as the drugs in use are only parasitostatic, and can induce toxicity. This study aimed at developing a drug delivery system for mefloquine, an antiparasitic compound which is highly active against E. multilocularis in vitro and in experimentally infected mice. We formulated mefloquine-loaded PLGA-PEG-COOH (poly-(lactic-co-glycolic acid)) nanoparticles that exhibit stable physical properties and mefloquine content. These nanoparticles crossed the outer acellular laminated layer of metacestodes in vitro and delivered their content to the inner germinal layer within less than 5 min. The in vitro anti-echinococcal activity of mefloquine was not altered during the formulation process. However, toxicity against hepatocytes was not reduced when compared to free mefloquine. Altogether, this study shows that mefloquine-loaded PLGA-PEG-COOH nanoparticles are promising candidates for drug delivery during AE treatment. However, strategies for direct parasite-specific targeting of these particles should be developed.
摘要：
泡状棘球蚴病（AE）是由多房棘球蚴幼虫期感染引起的严重疾病，元代码。由于没有实际的治愈性药物治疗，建议对AE患者进行根治性手术,并在2年内预防性给予阿苯达唑或甲苯达唑以预防复发.迫切需要新的治疗策略来管理AE，因为使用的药物只是抗寄生虫的，并能引起毒性。这项研究旨在开发甲氟喹的药物递送系统，一种抗寄生虫化合物，在体外和实验感染的小鼠中对多房性大肠杆菌具有高度活性。我们配制了负载甲氟喹的PLGA-PEG-COOH(聚(乳酸-共-乙醇酸))纳米颗粒,其表现出稳定的物理性质和甲氟喹含量。这些纳米颗粒在体外穿过外无细胞层压层，并在不到5分钟的时间内将其内容物输送到内生发层。在配制过程中,甲氟喹的体外抗包虫病活性没有改变。然而,与游离甲氟喹相比,对肝细胞的毒性没有降低.总之,这项研究表明，载甲氟喹的PLGA-PEG-COOH纳米颗粒是AE治疗期间药物递送的有希望的候选药物。然而,应开发针对这些颗粒的直接寄生虫特异性靶向策略.
