Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Department of Pharmaceutics, Faculty of pharmacy, Alexandria University, Alexandria, Egypt.
Acta Trop. 2020 Dec;212:105714. doi: 10.1016/j.actatropica.2020.105714. Epub 2020 Sep 17.
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.
血吸虫病的控制完全依赖于吡喹酮（PZQ）单药治疗，但由于对幼体阶段、再感染和新出现的耐药性的活性较低，治疗失败。如果通过单次口服剂量有效且安全地实现，提高 PZQ 的抗血吸虫治疗/预防特性是挽救该药物临床效益的明智选择。最近，我们开发了吡喹酮-米替福新脂质纳米胶囊（PZQ 250 mg/kg-MFS 20 mg/kg LNCs）作为一种纳米技术增强的新药组合，对曼氏血吸虫（S. mansoni）具有显著的多阶段活性，在小鼠模型中。本研究旨在提供该纳米组合具有化学预防作用的概念验证。在感染曼氏血吸虫之前一天和七天，用单剂量的纳米组合口服给予小鼠。纳米组合的保护作用相对于单独负载 PZQ 或 MFS 的 LNCs 和未治疗的感染对照，从寄生虫学和组织病理学方面进行评估。此外，还从生化和组织病理学方面评估了纳米组合的安全性。在感染前一天或七天给予纳米组合，与未治疗的感染对照相比，可显著降低平均虫体负荷和肉芽肿大小，并改善肝病理。尽管在感染前七天给予纳米组合的预防效果与感染前一天给予纳米组合相比显著降低，但仍存在。根据 PZQ 和 MFS 的作用谱及其互补的药代动力学（PK）特征，以及纳米包封对这些因素的影响，解释了结果。新型 PZQ-MFS 纳米组合在基于 PZQ 的大规模药物管理方案中具有重要的潜力，可提供根治、预防再感染和延缓对药物成分耐药性的发展。
