Abstract: AimTo study the effect of the liposomes coated by chitosan and its derivatives as oral dosage form for peptide drugs on the gastrointestinal (GI) transit of drugs. MethodsInsulin-liposomes were prepared by reversed-phase evaporation. The in situ perfusion experiment was used to investigate the enteral absorption of insulin. The hypoglycemic effects of insulin were investigated using the glucose oxidase method after administration in rats. The insulin concentrations of serum and enteral tissues were determined by radio-immunoassay in rats. ResultsIn in situ local intestinal perfusion experiment, the duodenum was the best segment for the absorption of the insulin liposomes coated by chitosan (CH) or chitosan-EDTA conjugates (CEC), and double-coated by CH-CEC; the colon was the best segment for the absorption of the insulin solution from rat intestine; but the best segment for the absorption of the uncoated and N-trimethyl chitosan chloride (TMC) coated insulin liposomes was unclear. In all segments, the enteral absorption of the insulin liposomes double-coated by CH-CEC was superior to that of other insulin liposomes. ConclusionThe insulin-liposomes coated by chitosan and its derivatives can enhance enteral absorption of insulin and increase stability of insulin in GI tract.