Abstract: 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 higherthan 9 % in comparison with subcutaneous injection of insulin. In addition, incomparison with subcutaneous injection of insulin, the relative bioavailability was 12.67 % calculated by area under the curve of serum insulin concentration versustime 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 toimproving oral bioavailability of insulin.

Key words: insulin, insulin, liposomes, liposomes, chitosan, chitosan, chitosan-EDTA conjugates, chitosan-EDTA conjugates, hypoglycemic effect, hypoglycemic effect