紫杉醇肺靶向微球的制备及体内外评价  

Preparation,in vitro and in vivo evaluation of actively lung targetable microspheres for paclitaxel delivery

作　　者：阎洲[1] 裴元英[1] 

机构地区：[1]复旦大学药学院药剂学教研室,上海200032

出　　处：《中国临床药学杂志》2006年第4期226-231,共6页Chinese Journal of Clinical Pharmacy

摘　　要：目的用生物可降解材料聚乳酸-聚羟基乙酸共聚物（PLGA）制备肺靶向紫杉醇缓释微球。方法在单因素考察的基础上进行正交试验设计，筛选出肺靶向紫杉醇PLGA微球的最佳制备工艺条件；利用桨板法研究了微球的体外释药规律；用小鼠为实验对象，研究了紫杉醇聚乳酸微球的体内组织药物分布。结果制得的微球形态圆整，粒径在5-15μm范围内的占总体积的87．18％，微球平均粒径为9.65μm；包封率为83．8％；载药量为19.7％；体外释药符合Higuehi方程Q=-2．1937＋22．009t^0.5，r=0.9904；体内实验表明紫杉醇微球混悬剂较普通注射剂更趋于聚集在肺组织。结论微球制备工艺稳定，具有明显的缓释作用和肺靶向性。AIM To optimize the preparation of sustained release microspheres of paclitaxel using the biodegradable materials- poly （lactic-co-glycolic acid） （PLGA）for lung targeting. METHODS The orthogonal test design was used to optimize the technology of preparation with good reproducibility. The surface morphology of the microspheres was observed by scanning electron microscope（SEM）.The formation of the drug microspheres was confirmed with differential scanning calorimeter（ DSC）. The mean diameter and the size distribution of microspheres, the drug loading, the incorporation efficiency, the reappearances of pharmaceutical technology, drug release in vitro, stability and tissue distribution after intravenous administration were examined. RESULTS Paclitaxel poly（lactic-co-glycolic acid） microspheres were regular in their morphology. Drug was enveloped in microspheres but not physically mixed with PLGA. The average particle size was 9.65μm with over 87.2 % of the microspheres being in the range of 5 - 15μm;the drug loading and the encapsulated ratio were 19.7 % and 83.8 % respectively. The reappearance of pharmaceutical technology was good. The in vitro release properties could be expressed by the Higuchi＇s equation： Q = 2. 193 7 ＋ 22.009 t^0.5, r = 0.990 4; Compared with injective solution, the drug in microspheres was more concentrated in lung tissue. CONCLUSION The technology of preparation was successful and paclitaxel poly（lactic-co-glycolic acid）microspheres show significant sustained release and lung trageting.

关 键 词：紫杉醇 聚乳酸-聚羟基乙酸共聚物 微球 肺靶向 

分 类 号：R943[医药卫生—药剂学] R96[医药卫生—药学]