Nanostructured lipid carriers for enhanced in vitro and in vivo schistosomicidal activity of praziquantel: effect of charge

WHO considers praziquantel (PZQ) as the drug of choice for treatment of Schistosoma mansoni infection but this requires high dose due to poor solubility and first pass metabolism. The aim of this work was to optimize nanostructured lipid carriers (NLCs) for enhanced PZQ oral delivery. The optimization involved testing the effect of surface charge of NLCs. NLCs comprised precirol ATO as solid lipid with oleic acid, Span 60 and Tween 80 as liquid components. Dicetyl phosphate and stearyl amine were the negative and positive charging agents, respectively. NLCs were prepared by microemulsification technique and were characterized. The schistosomicidal activity of PZQ loaded NLCs was monitored in vitro and in vivo using infected mice. PZQ showed high entrapment efficiency in all types of NLCs (ranged from 93.97 to 96.29%) with better PZQ loading in standard NLCs. This was clarified by thermal analysis which reflected displacement of PZQ by charging agents. In vitro schistosomicidal study revealed the superiority of PZQ loaded positively charged NLCs (LC50 and LC95 equal 0.147 and 0.193 mu g/ml respectively) with traditional and negatively charged NLCs being inferior to simple PZQ solution after short incubation period. Scanning electron micrographs showed that PZQ loaded positively charged NLCs resulted in more intense ultrastructural changes in worms. The superiority of positively charged NLCs was confirmed by in vivo assessment as they showed better improvement in histopathological features of the liver of the infected mice compared with other formulations. The study introduced positively charged NLCs as promising carriers for oral delivery of PZQ.