Wu Zheng-Hong, Ping Qi-Neng, Song Yun-Mei, Lei Xiao-Min, Li Jian-Ying, Cai Peng
Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
Yao Xue Xue Bao. 2004 Nov;39(11):933-8.
To evaluate the characteristics, the hypoglycemic efficacy and the pharmacokinetics of the insulin-liposomes double-coated by chitosan (CH) and chitosan-EDTA conjugates (CEC).
Insulin-liposomes were prepared by reversed-phase evaporation. The protection of insulin against peptic and tryptic digestion was studied with HPLC. The hypoglycemic effects of insulin-liposomes were investigated using the glucose oxidase method after oral administration to rats. Serum insulin concentration in rats were determined by radio-immunoassay, and were assessed by Pkanalyst computer program.
The insulin-liposomes double-coated by CH and CEC was shown to protect insulin against digestion of pepsin, trypsin and gastrointestinal contents. In glucose tolerance test in normal rats, as compared with phosphate buffer solution control group, the insulin-liposomes coated by CH and CEC could reduce the glucose-induced peak of hyperglycemia. The reduction of the insulin-liposomes double-coated by CH and CEC was superior to that of other insulin-liposomes. When administered intragastrically to normal rats, the insulin-liposomes coated by CH and CEC could reduce glycemia measured after an overnight fast. The hypoglycemic effect the insulin-liposomes double-coated by CH and CEC was superior to that of other insulin-liposomes, and the dosage of 50 mu x kg(-1) decreased by 45.98% of initial blood glucose level at 1 h. As compared with subcutaneous injection, the relative pharmacological bioavailability was 17.02% calculated by area under the curve of glucose level versus time profile after oral administration of the insulin-liposomes double-coated by CH and CEC to rats. The serum insulin concentration-time curves were found to best fit the one-compartment open model. As compared with subcutaneous injection, the relative bioavailability was 8.91% calculated by the area under the curve of serum insulin concentration versus time profile after oral administration of the insulin-liposomes double-coated by CH and CEC to rats.
The stability and absorption of insulin-liposomes double-coated by CH and CEC was superior to that of the insulin-liposomes coated either by CH, or by CEC respectively.
评估壳聚糖（CH）和壳聚糖 - 乙二胺四乙酸共轭物（CEC）双重包被的胰岛素脂质体的特性、降血糖效果及药代动力学。
采用逆相蒸发法制备胰岛素脂质体。用高效液相色谱法研究胰岛素对胃蛋白酶和胰蛋白酶消化的抵抗作用。给大鼠口服后，用葡萄糖氧化酶法研究胰岛素脂质体的降血糖作用。用放射免疫分析法测定大鼠血清胰岛素浓度，并通过Pkanalyst计算机程序进行评估。
CH和CEC双重包被的胰岛素脂质体显示出能保护胰岛素免受胃蛋白酶、胰蛋白酶和胃肠道内容物的消化。在正常大鼠的葡萄糖耐量试验中，与磷酸盐缓冲溶液对照组相比，CH和CEC包被的胰岛素脂质体能降低葡萄糖诱导的高血糖峰值。CH和CEC双重包被的胰岛素脂质体的降低效果优于其他胰岛素脂质体。给正常大鼠灌胃时，CH和CEC包被的胰岛素脂质体能降低过夜禁食后测得的血糖水平。CH和CEC双重包被的胰岛素脂质体的降血糖效果优于其他胰岛素脂质体，50μx kg(-1)的剂量在1小时时使初始血糖水平降低了45.98%。与皮下注射相比，给大鼠口服CH和CEC双重包被的胰岛素脂质体后，根据血糖水平与时间曲线下面积计算的相对药理生物利用度为17.02%。血清胰岛素浓度 - 时间曲线被发现最符合一室开放模型。与皮下注射相比，给大鼠口服CH和CEC双重包被的胰岛素脂质体后，根据血清胰岛素浓度与时间曲线下面积计算的相对生物利用度为8.91%。
CH和CEC双重包被的胰岛素脂质体的稳定性和吸收性优于分别由CH或CEC包被的胰岛素脂质体。
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