Bioavailability and in vivo efficacy of a praziquantel–polyvinylpyrrolidone solid dispersion in Schistosoma mansoni-infected mice

摘要

One of the problems of praziquantel (PZQ) is its very low aqueous solubility. Moreover, its dissolution rate is considered the limiting factor for its bioavailability. This work correlates the physical properties and the dissolution behavior of PZQ–polyvinylpyrrolidone (PVP) solid dispersion (SD) at the ratios of 1:1 and 3:7 with its oral bioavailability and its in vivo efficacy against Schistosoma mansoni (S. mansoni). The PZQ and PZQ–PVP SD were characterized by infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy (SEM) and solubility test. Results showed a decrease in crystallinity, possible interaction between PZQ and PVP, greater increase in dissolution rate and appreciable reduction in particle size. S. mansoni-infected mice treated orally with either pure PZQ or PZQ–PVP at a single dose of 500 mg/kg showed a higher increase in AUC(0–8h), C max, K a and t 1/2e with a significant decrease in k el versus the corresponding uninfected mice. Moreover, uninfected and infected mice treated with PZQ–PVP SD showed 2.3-, 1.6- and 1.3-, 1.25-fold increase, respectively, in AUC(0–8h) and C max, with a decrease in k el and increase in t 1/2e by twofold versus the corresponding pure PZQ-treated groups. Percentage worm reduction at all administered doses (62.5, 125, 250, 500 and 1,000 mg/kg) was significantly higher (1- to 1.5-fold) in mice treated with PZQ–PVP SD (ED50 = 40.92) versus those treated with pure PZQ (ED50 = 99.29). In addition, a significant reduction in total tissue egg load concomitant with a significant decrease in total immature and mature eggs and an increase in dead eggs in PZQ–PVP SD-treated groups versus their corresponding pure PZQ-treated groups was recorded. Solid dispersion of PZQ with PVP could lead to a further improvement in the effectiveness of PZQ therapy especially with the appearance of some PZQ-tolerant S. mansoni isolates.