Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Schistosomiasis is responsible for a considerable global disease burden. This work aimed to improve the therapeutic outcome of the only available antischistosomal drug worldwide, praziquantel (PZQ), by incorporating it into a novel carrier, 2solid lipid nanoparticles (SLNs)3, to enhance its solubility, bioavailability and efficacy. Asimple, cost-effective formulations of PZQ in solid lipid nanoparticles were tested in this work in experimental murine schistosomiasis with the aim of enhancing PZQ solubility, bioavailability and efficacy. PZQ in nanoformulation may overcome its known drawbacks (quick first pass metabolism in the liver) with its consequent reduced efficacy, specifically against the immature forms in the systemic circulation. SLNs has a superior advantage over common nanoformulations with respect to drug targeting, release, long-shelf stability, low toxicity, better bioavailability and compatibility with several routes of administration.Moreover, SLNs could resolve drawbacks, including undesirable taste, possible irritation and gastrointestinal adverse reactions with high safety margins and high biocompatibility over other conventional nanoformulations. Compared to market PZQ (M{u2010}PZQ), SLN{u2010}PZQ was more bioavailable, as denoted by higher serum concentrations in both normal and infected mice where elevated Ka, AUC0{u2013}24, Cmax, and t1/2e with a decrease in kel were demonstrated. In normal and S. mansoni{u2010}infected mice, SLN{u2010}PZQ was detectable in serum at 24 h, while M{u2010}PZQ completely vanished 8 h post{u2010}treatment. Additionally, enhanced absorption with extended residence time was recorded for SLN{u2010}PZQ

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