壳聚糖及其EDTA轭合物双层包覆胰岛素脂质体的处方工艺优化

目的:研究制剂因素对壳聚糖(CH)及其EDTA轭合物(CEC)双层包覆胰岛素脂质体降血糖作用的影响.方法:采用逆相蒸发法制得胰岛素脂质体,并用CH和CEC进行双层包覆.以小鼠口服降血糖效果作为实验指标,分别应用L16(215)和L8(27)正交实验设计优化CH-CEC双层包覆胰岛素脂质体的处方与工艺.结果:最佳处方组成为胰岛素100IU,pH 7.4磷酸盐缓冲液,磷脂150mg,胆固醇25mg,维生素E 15mg,0.2% CH 1.5mL和1% CEC 1.5mL.最佳制备工艺为乙醚10mL,旋转蒸发温度20℃,探针式超声时间0.5min,加CH和CEC后的孵化时间30min,孵化温度10℃,CH要先于CEC加入.经优化得到的双层包覆胰岛素脂质体经糖尿病模型大鼠口服后,具有平稳持久的降血糖作用,以皮下注射胰岛素为对照,其相对药理生物利用度(PA)达14.78%.结论:CH-CEC双层包覆胰岛素脂质体的组成和制备因素的变化会影响降血糖效果,用CH-CEC双层包覆的胰岛素脂质体具有较好降血糖作用.

Optimization of the formulation and process for the insulin liposome double-coated with chitosan and chitosan EDTA conjugates

Objective:To explore the effects of the formulation and the coating process on the treatment of hyperglycemia with the double-coated insulin liposome. Methods: The insulin liposome through reverse-phase evaporation was double coated with chitosan and chitosan EDTA conjugates. The formulation and the coating process were optimized with orthogonal design L16(215) and L8(27) respectively. The anti-hyperglycemic efficacy was measured in mice model. Results:The optimized insulin liposome showed a flat and sustained hypoglycemic effect with a relative pharmacological bioavailability of 14.78% in mice that were orally administrated,compared with the one in mice that were injected. Conclusion: Both formulation and process of the double-coated insulin liposome have a significant impact on the hypoglycemic effect.