尺寸均一的壳聚糖微球的制备.doc

M034 尺寸均一的壳聚糖微球的制备 王连艳 孟凡涛 马光辉 (中科院过程工程研究所生化工程国家重点实验室 北京 100080) 摘 要 虽然目前有数种传统方法应用于壳聚糖微球的制备中，但这些方法所制备的微球粒径均 一性差，这为应用上尤其是作为药物载体的应用带来很多缺陷，如药物包埋率低、靶向性差以及 在体内的生物利用度差。针对传统方法的缺点和不足，本研究将一种新型的微孔膜乳化技术应用 于壳聚糖微球的制备中，通过条件优化可制备出 CV 值低于 11％的粒径均一的微球，这将在药物 载体的应用中具有潜在的优势。 关键词 SPG 膜乳化 制备 壳聚糖 微球 中图分类号: R944.5 PREPARATION OF UNIFORM-SIZED CHITOSAN MICROSPHERES WANGN Lianyan, MENG Fantao and MA Guanghui (State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100080) Abstract There are a few methods to prepare chitosan microspheres, but the particle size distributions are broad by these methods, which bring many limitations on applications of drug controlled release systems, such as lower targetting function and low bio-availability. The aim of this study is to prepare uniform-sized chitosan microspheres. To realize this aim, a new emulsification method of membrane emulsification was used in this study. The results showed that the uniform-sized chitosan microspheres can be prepared by a hydrophobically modified porous membrane. Compared with conventional preparation methods, the particle size distribution is narrow and CV value is below 11%. Furthermore, a linear relationship between microsphere size with membrane pore size was found, so the microspheres with the required size can be prepared by choosing the membrane with adequate pore size. Membrane emulsification is an ideal preparation method of uniform-sized microspheres, and they have potential applications in drug formulation. Keywords membrane emulsification, preparation, chitosan, microsphere 引 言 壳聚糖作为一种阳离子的生物高分子，具有生物粘附性、生物相容性和生物降解性等优 1  良特性，而且其降解产物无毒、无免疫原性、无致癌性，壳聚糖的这些独特性使其成为应用 前景广阔的生物医药载体。壳聚糖作为生物医药载体主要是以微球或微囊的形式使用，而目 前壳聚糖微球或微囊的制备方法非常有限，主要采用乳化交联法、喷雾干燥法和复凝聚法等， 并且这些制备方法大多采用机械搅拌法制备乳液，所得乳液均一性差，最终导致所制得的壳 聚糖微球或微囊粒径很不均一。当作为药物载体时，粒径不均一会导致药物的包埋率低，载 体的靶向性差，最终导致药物在体内的生物利用度大大降低。 本研究针对传统壳聚糖微球制备方法的缺点和不足，以壳聚糖为载体材料、采用新型微 孔膜乳化结合交联法制备尺寸均一的药物载体。微孔膜是一种高度亲水性膜，不适合用