Aim To evaluate the gastrointestinal uptake of the insulin liposomes double-coated with chitosan(Ch) and chitosan-EDTA conjugates (CEC), and verify their efficiencies. Methods Insulin-liposomes were prepared by reversed-phase evaporation. The hypoglycemic effects of the insulin liposomes coated with Ch or/and CEC were investigated using the glucose oxidase method after oral administration in diabetic rats, normal rats, and beagle dogs. Serum insulin concentrations in beagle dogs were determined by radioimmunoassay and were assessed by Pkanalyst computer program. Results The animals fed the insulin liposomes coated with Ch or/and CEC were able to regulate better the glucose load than the animals receiving PBS or uncoated insulin liposome, and the regulative effects of the insulin liposomes double-coated with Ch and CEC were better than those of the insulin liposomes coated with Ch or CEC alone. After oral administration of the insulin-liposomes double-coated with Ch and CEC to animals, a significant (P＜0.05) blood glucose reduction was observed. Their relative pharmacological bioavailability was higher than 9 % in comparison with subcutaneous injection of insulin. In addition, in comparison with subcutaneous injection of insulin, the relative bioavailability was 12.67 % calculated by area under the curve of serum insulin concentration versus time profile after oral administration of the insulin-liposomes double-coated with Ch and CEC to beagle dogs. Conclusion The insulin-liposomes double-coated with Ch and CEC were conducive to improving oral bioavailability of insulin.%目的 研究壳聚糖和CEC双层包覆胰岛素脂质体的吸收状况,并验证其有效性.方法 采用逆相蒸发制备胰岛素脂质体;用酶-苯酚法测定血糖值;用放射免疫法测定血清胰岛素含量,并采用Pkanalyst程序进行拟合.结果 Ch-CEC双层包覆的胰岛素脂质体对负载葡萄糖的正常大鼠的血糖升高具有抑制作用;以皮下注射胰岛素(Ins)为对照,Ch-CEC双层包覆的胰岛素脂质体经糖尿病模型大鼠和beagle犬给药后的相对药理生物利用度均大于9%,具有较好的降血糖作用.另外,在beagle犬降血糖实验中,根据血清胰岛素浓度-时间曲线的曲线下面积(AUC)计算Ch-CEC双层包覆的胰岛素脂质体灌胃给药的相对生物利度为12.67%.结论 壳聚糖-CEC双层包覆胰岛素脂质体有利于改善胰岛素口服生物利用度.
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