Enhancement of the therapeutic efficacy of praziquantel in murine Schistosomiasis mansoni using silica nanocarrier.

The main objective of this work is preparation of mesoporous silica nanoparticles loaded with praziquantel (PZQ-Si) in order to enhance the therapeutic efficacy of praziquantel (PZQ). Mice were experimentally infected with Schistosoma mansoni and treated 6 weeks post-infection with PZQ in different doses via either oral or intraperitoneal (IP) routes. PZQ in the same doses orally administered to S. mansoni-infected mice was used as a drug control, and infected and non-infected non-treated mice served as positive and negative controls, respectively. PZQ-Si exhibited good physicochemical attributes in terms of small uniform size (105 nm), spherical shape, and PZQ entrapment efficiency (83%). A maximum antischistosomal effect was achieved using orally administered PZQ-Si as reflected by total worm burden, tissue egg count, oogram pattern, and hepatic granuloma count and diameter. The biomarkers related to liver oxidative stress status and immunomodulatory effect (serum TNF-α and IL-10) were significantly improved. Data obtained implied that IP route was less efficacious for the delivery of PZQ-Si. Encapsulation of PZQ permits the reduction of the used therapeutic dose of PZQ. Hepatic DNA fragmentation, measured by comet assay, was significantly improved in infected mice treated with maximum dose of PZQ-Si as compared to positive or PZQ control groups. The results indicate that mesoporous silica NP is a promising safe nanocarrier for PZQ potentiating its antischistosomal, antioxidant, immunomodulatory, and anti-inflammatory action in animal model infected with S. mansoni. From a practical standpoint, PZQ-Si using a lower dose of PZQ could be suggested for effective PZQ antischistosomal mass chemotherapy.