The Effect Of Solvent On Molecular States And Transdermal Delivery Of Praziquantel

The purpose of the research was to explore the effect of the nature of the solvent on molecular states and transdermal delivery of praziquantel(PZQ). The effects of the five different solvents,ethylene glycol phenyl ether(EGPE),tetrahydrofuran(THF),dimethyl sulfoxide(DMSO), oleic acid(OA)and 1,4-dioxane on molecular states of PZQ were studied by ultraviolet spectroscopy(UV) and Fourier transform infrared spectroscopy(FT-IR), respectively.The n-octanol/water partition coefficients of PZQ in the five different solutions were determined at 37℃and pH=7.4. Using New Zealand rabbits as experimental animals and the above five solutions of PZQ as transdermal agent, we studied the effects of nature of the solvents on transdermal delivery of PZQ. We explored the relative bioavailability of transdermal administration and oral administration at the same dosage and time for both methods.Transdermal PZQ delivery system that consists of solvent(EGPE) was applied to treating egg granuloma of rabbits infected with Schistosoma japonicum.The results showed that compared with those of pure PZQ, the UV absorption maximum wavelength of PZQ in the five solvents were all red-shifted and the characteristic absorption peaks of PZQ in infrared absorption spectrum changed as well,which indicated PZQ in the five solvents had different molecular states. The n-octanol/water partition coefficient of the above five solutions of PZQ was 0.90,-0.52,-0.13,0.39.-0.19,respectively,which clearly demonstrated that the nature of the solvents had a greater impact on molecular states of PZQ. New Zealand rabbits were transdermally administered using the above five solutions of PZQ. The time reached peak concentrations was 30min, 10min,15min,240min,30min, respectively, and the corresponding peak concentration was 17.82μg/mL,1.23μg/mL,2.08μg/mL,6.78μg/mL, 10.23μg/mL, respectively,which clearly indicated that solvent had a significant effect on the diffusion rate and diffusion capacity when PZQ came to the skin. The bioavailability of PZQ in EGPE, DMSO, OA solution via the transdermal route relative to oral PZQ tablets was 2.16,1.23 and 1.10,respectively,which showed that PZQ can better play the role in the fight against schistosomiasis in the form of transdermal delivery. Experimental treatment showed that eggs on the surface of liver of the rabbites decreased in treament group.Most of the volume of the egg granuloma was significantly reduced and parasite lysis and was absorbed in liver biopsy.This showed that the transdermal delivery of PZQ would be an effective way in schistosomiasis egg granuloma treatment.By studying the effect of solvents on molecular states and transdermal delivery of PZQ, we can find new solvent for transdermal delivery of PZQ and acquire a new understanding of the effect of molecular state of drug on transdermal delivery. We can also prove the mechanism of action of transdermal delivery of PZQ and establish a new method of transdermal delivery of PZQ for the treatment of schistosomiasis, which has theoretical and practical significance in completely control of schistosomiasis.