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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 osthole-Eudragit S100 nanoparticles (Ost-S100-NP) and its lyophilized preparation (Fd-Ost-S100-NP) Pharmacokinetics and relative bioavailability in rats. Methods: Ost-S100-NP colloidal solution and its lyophilized powder were prepared by emulsion-solvent diffusion combined with freeze-drying technique. The kinetics of in vitro release was studied by dynamic dialysis method. Ost concentration in plasma was measured by HPLC , 3P97 program to calculate pharmacokinetic parameters. Results: The average diameters of Ost-S100-NP and Fd-Ost-S100-NP were (55.4 ± 2.1) and (87.7 ± 2.3) nm, The drug release rate of the nanoparticles in the release media with pH> 6.0 increased significantly and had significant pH sensitivity. The pharmacokinetics of the drugs in rats were in accordance with the two-compartment model. Ost-S100-NP and Fd-Ost- The relative bioavailabilities of S100-NP were 161.1% and 118.4% of APIs, respectively. Conclusion: The pH-sensitive material Eudragit S100 is expected to be developed into a highly effective and low toxicity osthole nanoparticle.