载阿霉素的叶酸-壳聚糖微球的制备及其体外缓释性研究

为了提高阿霉素对肿瘤组织的靶向性,增强其抗肿瘤活性,延长其在人体内的作用时间。以壳聚糖为药物载体、叶酸为肿瘤靶向配体,在水相中采用离子交联法一步合成载阿霉素的叶酸-壳聚糖微球。利用动态光散射、透射电镜对微球的结构、平均粒径及粒径分布、形态特征、对药物的包封率及载药量、体外释放等特点进行了初步研究。结果表明:所制得的微球平均粒径为32.85μm。扫描电镜下观察其形态圆整,大小均匀,无粘连。对阿霉素包封率为(89.8±0.1)%,载药量为(20.5±0.1)%。在人工胃液pH=1.2及人工小肠液pH=6.8条件下具有很好的缓控释作用且无突释现象。

Preparation and characterization of doxorubicin loated folate-chitosan microspheres as a sustained-release drugs carrier

In order to enhance the tumor-targeting and anticancer activity of doxorubicin(DOX) and extend the in vivo effect of time,chitosan(CTS) was used as drug vector and folate(FA) as tumor targeting ligand.The doxorubicin-loaded microspheres composed of FA-conjugated CTS were prepared via an one-step ionic crosslinking approach in aqueous solution.The morphological characteristics of microspheres were examined using a transmission electron microscope(TEM).The average diameter of microspheres and size distribution were determined by dynamic light scattering.The drug encapsulation efficiency(EE),loading capacity(LC) and in vitro release characteristics were determined using ultraviolet spectrophotometer.It indicated that the microspheres display spherical appearance with uniform size of 32.85 μm.Optimized preparation parameters lead to the successful preparation of DOX-loaded folate-conjugated chitosan microspheres characterized with encapsulation efficiency and loading capacity of(89.8±0.1) % and(20.5±0.1) %,respectively.About 90% of DOX was released from microspheres in 8 h in artificial small intestinal fluid.The results indicate the microspheres have good delayed release effect without burst-releasing phenomena.