Praziquantel - chitosan nanoformulation against murine Schistosoma mansoni infection

Abstract

The aim of the present work was to design praziquantel (PZQ) loaded chitosan nanoparticles (PZQ-Cs) to improve the oral bioavailability and overcome the drawbacks of conventional PZQ therapy. The synthesized chitosan nanoparticles (CsNPs) were physico-chemically characterized by TEM and dynamic light scattering (DLS) with the calculation of the encapsulation efficiency (EE). PZQ was loaded into CsNPs in three different doses; reduced dose (250 mg/kg), high dose (500 mg/kg) and fully effective dose (1000 mg/ kg). Infected treated groups received either oral PZQ-Cs or oral PZQ alone 42 days post-infection and were sacrificed 2 weeks post-treatment. The current study revealed that PZQ-Cs induced a significant anti-schistosomal effect, compared to the infected non-treated control. However, on comparison with conventional PZQ treatment at the corresponding doses, oral PZQ-Cs showed a lower anti-schistosomal potential as reflected by the total worm burden, tissue ova count and oogram pattern. PZQ-Cs was significantly effective in attenuating the oxidative insult associated with S. mansoni infection, compared to the infected non-treated and PZQ treated groups. Genotoxicity assessment proved the safety of CsNPs, as they did not induce a significant DNA fragmentation in non-infected mice treated with blank CsNPs. The present work highlights CsNPs as safe, effective anti-inflammatory and antioxidant agents that could find a clinical use in the treatment of schistosomiasis induced oxidative stress and hepatic dysfunction. Further studies are recommended, however, to investigate how PZQ-Cs could be further modified to increase its anti-schistosomal potential.

Pathological and immunological evaluation of different regimens of praziquantel treatment in a mouse model of Schistosoma mansoni infection

“…In conjunction with the report of Fahmy et al [ 46 ], data from the present study showed that treatment of infected mice with 18 mg/kg/day of PZQ for 28 days during the larval and juvenile stages of the parasite significantly decreases the serum activities of ALT, AST, ALP, and total bilirubin concentration and increased γ-GT activity. Moreover, the primary cause of the metabolic dysfunction in schistosomiasis is the site-specific oxidative damage of some of the susceptible amino acids of protein [ 47 , 48 ]. Following the studies of Jatsa et al [ 19 , 34 , 35 ], the present study shows that S .…”