The control of schistosomiasis depends exclusively on praziquantel (PZQ) monotherapy with treatment failure due to minor activity against the juvenile stage, re-infection and emerging drug resistance. Improving the antischistosomal therapeutic/prophylactic profile of PZQ is a sensible option to save the clinical benefits of the drug if achieved effectively and safely via a single oral dose. Recently, we developed praziquantel-miltefosine lipid nanocapsules (PZQ 250 mg/kg-MFS 20 mg/kg LNCs) as a nanotechnology-enabled novel drug combination with significant multistage activity against Schistosoma mansoni (S. mansoni) in a murine model. The present study aimed at providing a proof of concept of the chemoprophylactic effect of this nanocombination. A single oral dose of the nanocombination was administered to mice one and seven days before challenge infection with S. mansoni. The protective effect of the nanocombination was assessed parasitologically and histopathologically relative to LNCs singly-loaded with PZQ or MFS and non-treated infected controls. In addition, the safety of the nanocombination was assessed biochemically and histopathologically. Administration of the nanocombination one or seven days pre-infection resulted in a statistically significant reduction in mean worm burden and granulomas size associated with amelioration of hepatic pathology compared to infected non-treated control. Although, the prophylactic effect was significantly reduced upon administration seven days pre-infection compared to administration one day pre-infection, yet, it still exists. Results were explained based on the spectrum of activity of PZQ and MFS and their complementary pharmacokinetic (PK) profiles in addition to the effect of nanoencapsulation on these factors. The novel PZQ-MFS nanocombination offers valuable potentials in PZQ-based mass drug administration programmes by granting radical cure, preventing re-infection, and delaying development of resistance to the component drugs.

血吸虫病的控制仅取决于吡喹酮（PZQ）单一疗法，由于针对少年期的小活性，再感染和新出现的耐药性导致治疗失败。改善PZQ的抗血吸虫病治疗/预防特性是明智的选择，如果通过单次口服有效有效地获得药物，可以节省药物的临床益处。最近，我们开发吡喹酮-米替福新的脂质纳米胶囊（PZQ 250毫克/千克-MFS 20mg / kg的LNCS），为纳米技术的使能与针对显著多级活性的新的药物组合曼氏血吸虫（曼氏血吸虫）。本研究旨在提供这种纳米组合的化学预防作用的概念证明。在用曼氏沙门氏菌攻击感染前一天和七天，对小鼠给予单次口服剂量的纳米组合。相对于单独装载PZQ或MFS的LNC和未治疗的感染对照组，在寄生虫学和组织病理学上评估了纳米组合的保护作用。另外，通过生物化学和组织病理学评估了纳米组合的安全性。与感染前未治疗的对照组相比，在感染前一或七天给予纳米组合可显着降低平均蠕虫负担和肉芽肿的大小，并具有改善肝脏病理的统计学意义。尽管与感染前一天给药相比，在感染前七天给药后预防效果显着降低，但是它仍然存在。除了纳米封装对这些因素的影响之外，还根据PZQ和MFS的活性谱及其互补的药代动力学（PK）曲线解释了结果。新型PZQ-MFS纳米组合通过给予彻底治愈，防止再次感染和延迟对成分药物的耐药性开发，在基于PZQ的大规模药物管理计划中提供了宝贵的潜力。