汉防己甲素缓释微囊肺靶向给药系统的研究

目的　制备肺靶向汉防己甲素缓释微囊 ,以提高药物降低肺动脉高压的作用并降低其毒性。方法　汉防己甲素用喷雾干燥 热变性微囊化 ,用UV测定汉防己甲素微囊的体外释放特性 ,用反相高效液相测定小鼠体内分布 ,经大鼠肺动脉插管测定其压力。结果　汉防己甲素微囊外观呈圆球形 ,带正电荷 ,载药量 37 88% ,微囊的体外释药规律符合Higuchi方程。小鼠肺部的药物浓度明显提高 ,平均滞留时间延长 ,大鼠肺动脉高压的降压作用从15 7 1h延长到 2 2 3 6h ,体内降压百分数与体外释药百分数之间具有相关性。结论　汉防己甲素经喷雾干燥 热变性微囊化可使其高效、低毒地治疗肺动脉高压

TETRANDRINE LOADED SUSTAINED RELEASE MICROCAPSULES FOR LUNG TARGETING

AIM To prepare lung targeted tetrandrine (TET) loaded sustained release drug delivery system by microencapsulation, decrease the toxicity and enhance the therapeutic function of anti pulmonary hypertension of TET. METHODS Albumin microcapsules were produced by spray drying thermal denaturation, a new technique. Some characterization of the prepared microcapsules was evaluated. Distribution of the microcapsules and their anti pulmonary hypertension effect in vivo were investigated. RESULTS The spherical microcapsules showed a drug loading of 37 88%. Compared to the original drug, the rate of TET released from the positively charged microcapsules in vitro was significantly decreased and fitted well by Higuchi equation. The TET concentrations in mouse lungs of TET microcapsules were significantly higher than those of TET injection, and the mean retained time of TET in lungs was prolonged from 157 1 h to 223 6 h after microencapsulation. The in vitro - in vivo correlation was established and confirmed ( P <0 001). CONCLUSION The new spray drying thermal denaturation method allows the preparation of drug loaded albumin microcapsules with desired results. The prepared microcapsules were found to have the potential function of delivering TET to pulmonary artery via iv, with low toxicity and high efficacy.