Effects of the liposomes coated by chitosan and its derivatives on the gastrointestinal transit of insulin / 药学学报

<p><b>AIM</b>To 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.</p><p><b>METHODS</b>Insulin-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.</p><p><b>RESULTS</b>In 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.</p><p><b>CONCLUSION</b>The insulin-liposomes coated by chitosan and its derivatives can enhance enteral absorption of insulin and increase stability of insulin in GI tract.</p>

Studies on the insulin-liposomes double-coated by chitosan and chitosan-EDTA conjugates / 药学学报

<p><b>AIM</b>To evaluate the characteristics, the hypoglycemic efficacy and the pharmacokinetics of the insulin-liposomes double-coated by chitosan (CH) and chitosan-EDTA conjugates (CEC).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>