Abstract: Chitosan and Gelatin are good biocompatible polymers and are suitble for drug carriers. Preparation of 5-fluorouracil loaded chitosan/gelatin particles and in vitro release were performed using emulsion crosslinking method with paraffin oil as external phase and chitosan/gelatin as internal phase, and the optimal formulations were verified by orthogonal design. The drug loading, encapsulation efficiency, the microscopic morphology and release behavior of drug loaded particles in vitro were examined. The optimal preparation conditions were:the ratio of water to oil 1:7, the ratio of chitosan/gelatin concentration 1:3, emulsifying time 5min, emulsifying temperature 60℃, glutaraldehyde dosage 5.5mmol/L, reaction time 1h, and emulsifier dosage 100.7mmol/L. Under these conditions, the drug loading of particles was 34.96% and encapsulation efficiency was 38.36%. Infrared spectroscopy showed that chitosan/gelatin microparticles have loaded 5-Fu. Microparticles were spherical with smooth surface. 5-Fu can be encapsuoed in chitosan/gelatin by emulsion crosslinking method. This method was simple and reproducible and drug release performance in vitro showed that the microparticles had obviously sustained release effect.

Key words: preparation, optimal design, support, chitosan, gelatin, 5-fluorouracil, in vitro drug release

摘要： 壳聚糖及明胶是生物相容性良好的高分子药物载体,制备载5-氟尿嘧啶壳聚糖/明胶微粒,并进行体外释药研究。以石蜡油为外相,壳聚糖/明胶为内相,用乳化交联法制备微粒,以吸附药量为指标,采用正交设计实验优化获得最佳制备条件,用红外光谱、SEM对最佳条件下制备的微粒进行表征。结果表明壳聚糖/明胶微粒的最佳制备条件如下:水油比1:7,壳聚糖/明胶浓度比1:3,乳化剂100.7mmol/L,乳化5min,乳化温度60℃,交联剂戊二醛用量5.5mmol/L,交联时间1h。在此条件下,载药微粒的载药量为34.93%,包封率为38.36%。红外光谱图表明壳聚糖/明胶微粒已负载5-氟尿嘧啶,SEM表明微粒成球状,表面较光滑。模拟胃肠释放表明,微粒具有一定的缓释性能。采用乳化交联法制备载5-氟尿嘧啶壳聚糖/明胶微粒方法简单,重现性好,且其体外释放实验显示出明显的缓释作用。

关键词: 制备, 优化设计, 载体, 壳聚糖, 明胶, 5-氟尿嘧啶, 体外释药