山奈酚肠溶复合纳米粒的体外释放和药代动力学研究

In Vitro Release and Pharmacokinetics Study of Enteric-coated Kaempferol Loaded Nanoparticles

目的:研究山奈酚肠溶复合纳米粒的体外释放行为和大鼠体内药代动力学特征。方法:动态透析法考察处方在pH=1.0和pH=6.0介质中的体外累积释放率,绘制释放曲线;分别采用一级、Higuchi、Ritger-Peppas和Weibull方程进行拟合,分析释药原理;采用HPLC测定大鼠灌胃给药后血浆中山奈酚浓度,利用DAS 2.0软件计算主要药动学参数。结果:肠溶包衣后,山奈酚纳米粒在pH=1.0介质中0~4 h内几乎无释放,而在pH=6.0介质中0~4 h的累积释放率可达28.77%,释放曲线经拟合与Higuchi方程相关性最好,Ritger-Peppas方程拟合结果n>0.89;肠溶复合纳米粒中药物在大鼠体内的平均驻留时间(MRT0-t)和达峰时间(Tmax)较未包衣纳米粒分别延长了2.29、2.66 h,差异具有统计学意义(P<0.05)。结论:肠溶衣的包覆有效抑制了纳米粒中山奈酚在胃酸环境下的释放,释药机制为扩散与溶蚀作用相结合;药动学结果表明,山奈酚肠溶复合纳米粒具有小肠定位释放性能,明显延长了山奈酚在大鼠体内的滞留时间,具有缓释作用。

Objective:To investigate the in vitro release behavior and pharmacokinetic characteristic of enteric-coated kaempferol loaded nanoparticles in rats.Methods:Dynamic dialysis method was used to investigate the in vitro cumulative release rate in pH=1.0 and pH=6.0 medium,and the release curve was drawn.Fitted the release curve by the first-order,Higuchi,Ritger-Peppas and Weibull equations to analyze the principle of drug release.The concentration of kaempferol in plasma after gastric administration was determined by HPLC,and the main pharmacokinetic parameters was calculated by DAS 2.0 software.Results:The cumulative release rate was almost 0% at 0~4 h in pH=1.0 medium while 28.77% in pH=6.0 medium after enteric coating.The curve of release was best correlated with Higuchi equation and the fitting result of Ritger-Peppas equation was n>0.89.The mean residence time(MRT0-t)and peak time(Tmax)of enteric-coated nanoparticles in rats were 2.29 and 2.66 hours longer than those of uncoated nanoparticles,respectively,with statistical difference(P<0.05).Conclusion:The enteric coating inhibited the release of kaempferol under gastric acid environment effectively,and the mechanism of drug release was the combination of diffusion and dissolution.The pharmacokinetic results showed that enteric-coated nanoparticles achieved at intestines department release request,prolonged the retention time of kaempferol in rats and had a sustained release effect.