丙硫异烟胺肺靶向微球的制备及体内外评价

Preparation and Evaluation of Lung Targeting Microspheres for Protionamide in vitro and in vivo

目的探索用乳酸．羟基乙酸共聚物（PLGA）微球静脉给药实现抗结核药丙硫异烟胺肺部靶向输送的可行性。方法利用单因素分析方法，筛选出丙硫异烟胺-PLGA微球制备的最佳工艺条件；利用浆法研究了载药微球体外释药的规律；利用BALB／C小鼠研究了丙硫异烟胺PLGA微球静脉给药后的体内组织分布。结果制得的微球形态圆整，微球平均直径为（9．86±1．38）μm，粒径在7～15μm的占81．53％；丙硫异烟胺的包封率为（32．70±0．37）％，载药量为（8．48±0．24）％；丙硫异烟胺PLGA微球体外释药符合Higuchi方程（Q=4．4303t1/2。＋7．7241），释药较慢；体内分布试验表明，微球混悬剂静脉给药后丙硫异烟胺在肺中的浓度显著高于普通注射剂，而且保持较长时间。结论微球制备工艺稳定，具有可重复性，微球有明显的缓释作用和肺靶向性。

Objective To testify the feasibility of targeted delivery of protionamide to lung through the iv administration of the biodegradable poly（lactic-co-glycolic acid） （PLGA） microspheres. Methods Based on the single-factor study, the preparation of protionamide-PLGA microspheres was optimized. The surface morphology of the microspheres was observed by scanning electron microscope（SEM）. The mean diameter and the size distribution of microsphere, the drug loading, the incorporation efficiency, drug release in vitro, stability and tissue distribution after intravenous administration were also evaluated, respectively. Results Protionamide-PLGA microspheres were regular and spherical in shape. The average particle size was （18.86±1.38） pin and over 81.53 % of the microspheres was in the range of 7-30 prn. The drug loading and encapsulated ratio was （32.70±0.37）% and （8.48±0.24）%, respectively. The in vitro drug release could be well fitted by the Higuchi equation （Q=4.4303 t1/2±7.7241, r=0.9913）. Compared with the aqueous formulation, the drug level in lung of BALB/C mice in microsphere group was much higher, and also kept for longer time. Conclusion The protionamide-PLGA microspheres prepared in this study showed significant sustained release and lung targeting effect.