利福平PLGA纳米粒的制备及雾化吸入给药后在大鼠体内的药动学

摘要

Objective]To prepare Rifampicin-loaded PLGA nanoparticles and evaluate the in vitro release behavior and the pharmacokinetics of the nano-particles in rats. [Method] The rifampicin nanoparticles with PLGA as carrier material were prepared by a modified spontaneous emulsification solvent dif-fusion method and characterized in terms of shape, particle size, encapsulation efficiency and drug loading. The in vitro release behavior was determined by dialysis method and the pharmacokinetics of the nanoparticles after nebulized inhalation in rats was evaluated. [Result] The optimal nanoparticles were spherical with the mean diameter of(128.73±4.07)nm. The encapsulation efficiency was(65.84±1.08)%and drug loading was(3.78±0.14)%. The phar-macokinetics results showed that tmax of nanoparticles group was increased by 6 times while the Cmax was nearly 30% lower than the solution group. [Con-clusion] Rifampicin-loaded PLGA nanoparticles were successful y prepared by a modified spontaneous emulsification solvent diffusion method. The nanoparticles with slower absorption after nebulized inhalation as wel as the less general exposure dose would be worthy of further study.%　　[目的]制备利福平PLGA纳米粒，考察其体外释放特性并评价该纳米粒在大鼠体内的药动学特征。[方法]以乳酸-羟基乙酸共聚物（PLGA）为载体，采用改良的自乳化溶剂蒸发法制备利福平PLGA纳米粒，考察其形态、粒径、包封率、载药量，采用透析袋法研究其体外释放特性，考察纳米粒经雾化吸入给药后在大鼠体内的药动学特征。[结果]制备的纳米粒外观呈球形或类球形，平均粒径为（128.73±4.07）nm，包封率和载药量分别为（65.84±1.08）%和（3.78±0.14）%。药动学结果显示，纳米粒组的tmax是溶液组6倍，Cmax比溶液组降低30%。[结论]采用改良的自乳化溶剂蒸发法可成功制备利福平PLGA纳米粒；经雾化吸入给药后，能显著减缓利福平进入体循环的速度并使药物全身暴露减少，具备进一步开发价值。