| Schistosomiasis is an infectious disease with great harm to human and livestock. It may cause serious diseases in liver or intestinal canal such as cirrhosis, leading to loss of labor or even death in patients. Praziquantel(PZQ) was recommended as the preferred drug for treating schistosomiasis. But the strong first-pass effect of PZQ, and low bioavailability, might limit its application in oral administrationIn this article, a series of transdermal agent systems with transdermal enhancers in different solvents, including volatile and non-volatile solvents, were prepared. The solubilities of PZQ in different transdermal agents and the pharmacokinetic property were determined by UV-Vis spectrophotometer and HPLC. The optimum transdermal agents screened out by evaluation of the bioavailability after administration via skin was used to give experimental treatment for mice and rabbits infected with Schistosomiasis. The results show that the solubility of PZQ in the mixture of ethylene glycol phenyl ether and ethanol is 429 mg-mL"1 in the temperature of 37℃when the proportion of ethanol is 50%. In the mixture of dioxane and ethanol with the proportion of ethanol ranging from 0% to 30%, the solubility of PZQ is ranged from 419 to 445 mg·mL-1 which is decreasing with the increasing of ethanol. It is much higher than the values of documents.The Cmax value of PZQ in serum was 35.93μg/mL at the time of 120min after the transdermal administration of evaporation delivery system that contained ethanol was 50% of mixture of solvents. The Cmax was 6.3-fold that oral administration. And also the transdermal administration of evaporation delivery system had the highest bioavailability.At the abdominal part of mice infected with Schistosoma japonnicum, the worm-reduction rate was achieved 92.86%,100%,100%, and the egg-reduction rate was 93.51%,100%,100% when the transdermal delivery system of PZQ at the concentration of 70μg/mL,150μg/mL,200μg/mL were transdermally administered, respectively. Then the New Zealand rabbits infected with Schistosoma japonnicum were transdermallly administered using transdermal evaporation delivery system of PZQ at concentration of 300mg/mL, it was observed that the egg granuloma reduction rate in liver of the rabbits achieved at 77%. Compared with infectation control group, the injury of liver tissue of treatment group was markedly lightened and the pathological changes of egg granuloma in liver was somewhat slowed down.The transdermal evaporation delivery system of PZQ provides an effective and convenient way to treat Schistosomiasis of human and livestocks by raising the bioavailability of PZQ. It has great significance and promising future for the treatment of Schistosomiasis. |
