羟基喜树碱微球的制备及其小鼠体内分布研究

目的:制备肺靶向性羟基喜树碱(HCPT)微球,评价其体外释药特性及其在小鼠体内的肺靶向性。方法:以聚乳酸为主要辅料,采用溶剂挥发法制备微球,考察其粒径、包封率、载药量,比较微球及原料药的体外释药性;取12只小鼠分别尾静脉注射HCPT微球及原料药,30min后分别测定血浆及各组织的药物浓度并计算相对分布率。结果:所制微球粒径在7～30μm者达81.6%,平均粒径为(14.2±3.1)μm,包封率为72.36%,载药量为(40.6±3.6)%,微球及原料药体外释药参数T50分别为85、18min。微球给药组在肺中的药物浓度最高(32.2±2.48)μg.mL-1,相对分布率58.1%;原料药给药组在血浆中的药物浓度最高(13.52±2.58)μg.mL-1,相对分布率25.24%。结论:所制HCPT微球具有明显的缓释性及肺靶向性。

Preparation of Hydroxycampothecinum Microspheres and Its Distribution in Mice

OBJECTIVE： To prepare lung - targeting hydroxycampothecinum（HCPT） microspheres and evaluate its in vitro release characteristics and its lung- targeting property in mice. METHODS： The microspheres was prepared by solvent volatilization with polylactic acid as chief excipient. The particle size, entrapment efficiency（EE） and drug loading（DL） of the microspheres were studied and the in vitro release rate was compared with that of the crude drug. 12 mice enrolled were injected via vena caudalis with HCPT micropheres or HCPT crude drug, at 30 min, the drug level in plasma and tissues were determined and the relative distribution rates（RDR） were computed. RESULTS： 81.6% of the microspheres ranged from 7- 30μm in particle size, the mean diameter was （14.2± 3.1）μm, the EE was 72.36%, the DL was （40.6± 3.6）%, and the in vitro drug release parameter T50 was 85 min for microspheres vs. 18 min for crude drug. The drug level of the microspheres in lung was the highest at （32.2± 2.48）μg .mL^-1 with a RDR of 58.1% ; The drug level of the crude drug group in plasma was the highest at （13.52± 2.58）μg . mL^-1 with a RDR of 25.24%. CONCLUSION： The prepared HCPT microspheres had the distinctive characteristics of sustained- release and lung targeting.