新型栓塞剂磺酸基巯基壳聚糖微球的物理性质和释药特性体外评价

Physical property and in vitro drug release evaluation of a novel sulfonic-thiol-chitosan microsphere

目的:体外评价磺酸基巯基壳聚糖微球(简称STCH)的物理性质和释药特性。方法:①通过乳化交联法制备空载微球并观察其形态;②分别考察空载微球和载药微球(加载阿霉素)的溶胀度和溶胀速率;③通过导管推注试验考察载药微球在使用中的形态变化;④采用T型装置考察载药微球的释药特性。结果:成功制备直径在100～300μm的空载微球,其表面形态圆整光滑;空载微球在生理盐水中约30 min后达到溶胀平衡,体积膨胀为最初的3.0倍,吸水量为微球原重量的9.5倍;载药微球在磷酸盐缓冲液中(pH=6.8)约50 min后达到溶胀平衡,体积膨胀为最初的1.18倍,吸水量为微球原重量的0.2倍;微球在通过5F导管时没有发生明显形变;微球释药时间持续7 d以上,无突释现象,其释药曲线符合Higuchi方程。结论:初步试验证实磺酸基巯基壳聚糖具有良好的物理性质和释药特性,具有载药、释药、栓塞3种功能,是介入治疗领域所需的新型栓塞剂。

Objective： To investigate the physical property and in vitro drug release of sulfonic-thiol-chi- tosan microsphere （STCM）. Methods： Empty microsphere was prepared by emulsification cross-linking method and then observed under an electron microscope. Swelling characterization of unloaded microsphere and drug-load- ed microsphere （loaded with doxorubicin） was detected. Deformation of drug-loaded microsphere passed through 5F catheter was observed, and drug release was detected in a T instrument. Results ： The shape of unloaded micro- sphere was smooth and rounded with diameters of 100 - 300 μm. The volume expansion was 3 times and the amount of water absorbed was 9.5 times of initial volume and weight of unloaded microsphere, respectively. When swelling equilibrium was reached about 30 min later in saline, the volume expansion was 1.18 times and the amount of water absorbed was 0.2 times of initial volume and weight of drug loaded microsphere, respectively. When swelling equi- librium was reached about 50rain later in phosphate buffer （pH = 6. 8） , the shape of drug loaded microsphere changed little after passed through 5F catheter, the drug release lasted for 7 days and showed no burst release. The release curve was in accordance with Higuchi equation. Conclusion： This preliminary tests shows that STCM has good physical properties, and drug loading, drug release and embolic characterization in vitro, which are required as new embolic agent in interventional treatment.