采用喷雾干燥法制备胸腺喷丁羧甲基壳聚糖鼻黏膜给药微球,通过正交设计优化处方,采用透析袋法研究其体外释药特性,并测定了载药微球对免疫抑制大鼠T淋巴细胞CD4+/CD8+值的影响。结果表明,所制备的微球圆整,平均粒径为(40.60±0.30)μm,包封率为(59.80±0.61)%,载药量为(15.30±0.25)%。体外释药曲线符合Higuchi方程。与阴性对照(生理盐水)组相比,大鼠鼻黏膜给予高、中、低剂量(0.43、0.30、0.23mg/kg)载药微球后均能明显提高T淋巴细胞CD4+/CD8+值,其中高剂量载药微球组与阳性对照组(胸腺喷丁注射液,0.1mg/kg)无显著差异(P〉0.05)。
The carboxymethyl chitosan microspheres loaded with thymopentin for nasal administration were prepared by spray drying technique. The preparation was optimized by orthogonal design. The drug release behavior in vitro was determined by dialysis method. The effects of thymopentin-loaded microspheres on the ratio of CD4+/CD8+ of T-lymphocytes in immunosuppressed rats were also examined. The optimal microspheres were spherical with the mean diameter of (40.60±0.30)~tm. The entrapment efficiency was (59.80±0.61) % and drug loading was (15.30±0.25) %. The in vitro release curve fitted to Higuchi equation. Compared with the negative control (saline) group, the CD4+/CD8+ ratios of high, middle and low dose (0.43, 0.30, 0.23 mg/kg) microspheres groups after nasal administration were signifi- cantly increased. There was no significant difference between high dose microspheres group and positive control (thymo- pentin injection, 0.1 mg/kg) group (P〉0.05).