الفهرس 
first RESEARCHOnly 14 pages are availabe for public view
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Abstract
Schistosomiasis is one of the neglected tropical diseases affecting the poor segments of a population. The control depends exclusively on praziquantel (PZQ) with shortcomings including treatment failure, reinfection, and emergence of drug resistance. Thus, there is an urgent need to search for an effective and safe alternative approaches for schistosomiasis control. The aim of the present study was to enhance the antischistosomal therapeutic activity of PZQ by its co-administration with miltefosine (MFS) in a single oral fixed-dose nanocombination therapy.
Two fixed-dose nanocombinations were prepared to provide 250 mg praziquantel- 20 mg miltefosine/kg (high fixed-dose) and 125 mg praziquantel- 10 mg miltefosine/kg (low fixed-dose) encapsulated in lipid nanocapsules (LNCs). Their antischistosomal efficacy in comparison to a non-treated control and their praziquantel singly loaded counterparts was assessed in murine schistosomiasis mansoni. A single oral dose of either formulation was administered on the initial day of infection, 21st, and 42nd day p.i. Scanning electron microscopic (SEM), parasitological, and histopathological studies were used for assessment.
The LNCs (~ 58 nm) showed high entrapment efficiency of both drugs (> 97%). Compared to singly loaded praziquantel-LNCs, the higher nanocombination dose showed a statistically significant decrease in mean worm burden, particularly against invasive and juvenile worms, granuloma size, and amelioration of hepatic pathology. In addition, SEM examination of adult male worms showed extensive dorsal tegument damage with noticeable deposition of nanostructures of the size of LNCs.