Study Of Lipid Nanoparticle Containing Praziquantel

By now, praziquantel is the most useful and safe antimony, which is still widely applied for the prevention and cure of schistosomiasis. But the clinical therapeutic effect was limited because of the extremely low oral bioavailability caused by first pass effect. In order to improve the oral bioavailability, the formulations of solid lipid nanoparticle and liposome with praziquantel (PZQ) as a model drug were studied.An HPLC method with methanol-water (70/30, v/v) as mobile phase was developed for the assay of PZQ in formulation. The analysis method was precise, simple and reliable. And the Sephadex G50 mini-column method was developed for determining the entrapment efficiency (EE) of lipid nanoparticles.Ultrasonic method was used to prepare PZQ-SLN dispersion, ultrasonic time and intensity were key factors for the preparation of SLN. Small particle size and high entrapment efficiency could be acquired with Compritol 888 ATO and butyl acetate as lipid carrier, Soybean lecithin/Poloxamer188/ sodium stearate as emulsifiers. With the criteria of entrapment efficiency, orthogonal design experiments were performed to optimize the process parameters. Many physicochemical characteristics of PZQ-SLN were investigated. The appearance of SLN was spheric particle with mean size of 100 nm, theζpotential was -66.3mV, the encapsulation efficiency was about 80%. Results of the release experiments indicated that the release rate of PZQ from PZQ-SLN accorded with Weibull equation with an initial burst effect followed by a slower rate stage. A part of drug might be adsorbed in the surface and some embed in the SLN. Stability experiments results indicated that PZQ-SLN should be stored at 4℃.Film dispersion method was used to prepare the PZQ liposome. The formulation components and the manufacture factors were optimized by orthogonal design, and the pharmaceutical properties of sample were also evaluated. The results indicated that the ultrasonic time and the concentrations of lecithin, cholesterol and PZQ could affect the trapping efficiency of PZQ. Liposomes containing PZQ with an average trapping efficiency 87%, size of 100nm, and zeta potential of- 26.8mV were obtained. Results of the release experiments indicated that the release rate of PZQ from PZQ-Lip accorded with Weibull equation with an initial burst effect followed by a slower rate stage. Stability experiments results indicated that PZQ-Lip should be kept stable at 4℃. An HPLC method was developed for the determination of PZQ in the plasma of rats. Oral pharmacokinetic behaviors of PZQ tablets, PZQ-Lip and PZQ-SLN were investigated in rats. According to the concentration of PZQ- time curve, C_max of PZQ obtained from rats administration of tablets was 2.14μg/mL and T_max was 0.25h; C_max of PZQ from samples of PZQ-Lip was 5.96μg/mL and T_max was 0.8h; C_max of PZQ from samples of PZQ-SLN was 2.4μg/mL, 2.59μg/mL, and T_max was 0.25h, 4.0h respectively. The MRT of PZQ solution, PZQ-Lip and PZQ-SLN were 1.99h, 2.61h, 4.11h separately. The AUC0-∞showed that compared with PZQ tablets, PZQ-Lip and PZQ-SLN significantly enhanced the oral bioavailability. So liposomes and SLN might be applied for the therapy of schistosomiasis through peroral administration.