卡铂微囊的制备及其在小鼠体内的组织分布

Preparation of Carboplatin Microcapsules and Tissue Distribution in Mice

目的：优化卡铂乳酸／羟基乙酸共聚物微囊的制备处方并考察其在小鼠体内的组织分布。方法：采用乳化-溶剂挥发法制备载药微囊．U15均匀设计表筛选提高包封率和控制粒径分布的条件。以卡铂原料药为对照，等离子体原子发射光谱法测定小鼠单剂量尾静脉注射给药后0．08～48h各组织中的药物浓度。结果：优化处方所得载药微囊粒径为（14．25±3．52）μm．载药量为（6．81±0．04）％，包封率为（74．13±0．56）％（n=3）。与原料药对照，卡铂微囊在肺组织中的药物峰浓度增加1．76倍，药物分布百分率较高（31．97％～45．59％）；而心脏和肾组织中的药物峰浓度降低、药时曲线下面积减小。结论：优化工艺合理，重现性良好。卡铂微囊在肺组织的药物浓度和分布百分率均较高，呈明显的肺靶向效应。

OBJECTIVE： To optimize the preparation of carboplatin-poly（DL lactide/ glycolide） microeapsules and study its distribution in mice in vivo. METHODS： Carboplatin microcapsules were prepared by emulsion- solvent evaporation technique, the U15 uniform experimental design was chosen to optimize the preparation. From 0.08 to 48 hour after iv single dose administration, carboplatin concentration in tissues respectively were measured by inductively coupled plasma- atomic emission spectrometry. RESULTS： The average diameter of the optimized microcapsules were（14.25 ± 3.52） μm, the drug loading and entrapment efficiency （6.81 ± 0.04）% and （74.13 ± 0.56）% （n =3） respectively. The experiments in tissue distribution showed the peak value of carboplatin microcapsules in lungs were increased 1.76 times compared with earboplatin, and the percent of distribution were contained from 31.97% to 45.59% after injection. On the contrary, the peak value and area under the curve of carboplatin mieroeapsules in the kidney and the heart were decreased compared with carboplatin. CONCLUSIONS： The results and reproducibility of optimized preparation procedure was good. The higher carboplatin concentration and distribution percent of carboplatin microcapsules in lungs, which showed remarkable lung- targeted effects.