蛇床子素-pH敏感性纳米粒的制备及其在大鼠体内的药代动力学

Preparation of pH-sensitive osthol-nanoparticles and its pharmacokinetics in rats

目的:制备蛇床子素-Eudragit S100纳米粒(Ost-S100-NP)及其冻干制剂(Fd-Ost-S100-NP),并考察相关特性;考察蛇床子素、纳米粒制剂和冻干制剂在大鼠体内的药代动力学及相对生物利用度。方法:以乳化-溶剂扩散法联合冷冻干燥技术制备Ost-S100-NP胶体溶液及其冻干粉末;动态透析法研究其体外释药动力学;以HPLC测定大鼠灌胃后血浆中的Ost浓度,3P97程序计算药代动力学参数。结果:Ost-S100-NP和Fd-Ost-S100-NP的平均粒径分别为(55.4±2.1)和(87.7±2.3)nm;包封率>95%;电镜下呈均匀规则的圆球形;且纳米粒制剂在pH>6.0的释放介质中释药速率明显增大,具有显著pH敏感性;药物在大鼠体内药代动力学均符合二室模型,Ost-S100-NP和Fd-Ost-S100-NP的相对生物利用度分别为原料药的161.1%和118.4%。结论:以pH敏感性材料Eudragit S100为载体有望开发成一种高效、低毒的蛇床子素纳米制剂。

Objective： To prepare osthol-Eudragit S100-nanoparticles（Ost-S100-NP） and Fd-Ost-S100-NP,and to investigate the bioavailability and the pharmaceutical characteristics of Ost-S100-NP in SD rats.Methods： Ost-S100-NP was prepared by an emulsion-solvent diffusion method and a freeze-drying technique.Dynamic dialysis method was used to determine the in vitro release dynamics of Ost-S100-NP and Fd-Ost-S100-NP.The concentration of Ost-S100-NP was determined by HPLC and its pharmacokinetics parameters were calculated by 3P97 program.Results： The particle sizes of Ost-S100-NP and Fd-Ost-S100-NP were（55.4±2.1） and（87.7±2.3） nm.The encapsulation efficiency was over 95%.The drug-loaded nanoparicles were spherical as observed by transmission electromicroscopy.The in vitro release experiment showed an evidently pH-sensitive property when the medium pH was over 6.0.The relative bioavailability of Ost-S100-NP and Fd-Ost-S100-NP were 161.1% and 118.4% compared with Ost.Conclusion： pH-Sensitive Eudragit S100 is a potential carrier material in developing a high performance Ost nanometer system with low toxicity.