Aims/hypothesis: The development of an orally active insulin formulation will offer great advantages over conventional injectable insulin therapy in the treatment of patients with diabetes mellitus. Since insulin absorption in the intestine is restricted by the natural physiological characteristics of insulin, we developed a small synthetic compound, Nα-deoxycholyl-L- lysyl-methylester (DCK), as an insulin carrier to enhance oral delivery. Methods: Streptozotocin-induced diabetic rats orally received single doses of insulin (42 U/kg) or insulin/DCK formulation (10, 21, 30 and 42 U/kg) under fasting conditions. Blood glucose levels and plasma insulin concentrations were measured for 6 h following the administration of the agents. An OGTT was also performed immediately after the administration of the oral insulin/DCK formulation. Results: The administration of 21, 30 and 42 U/kg (based on insulin activity) of insulin/DCK formulation reduced plasma glucose levels by up to 33.0% (median; range 30.6-70.2%), 78.5% (39.4-86.8%) and 75.2% (67.0-87.4%), respectively, compared with baseline levels. Furthermore, plasma insulin concentrations were observed to rapidly increase. In the OGTT, the insulin/DCK formulation reduced the AUC0-240 for glucose by 30.8% (22.3-54.9%) (p<0.01), and stabilized glycaemia for up to 4 h. Conclusions/interpretation: The results of this study demonstrate that the insulin/DCK formulation can be absorbed in the intestine and that it is biologically efficacious. We therefore suggest that this oral formulation could be used as an alternative to injectable insulin with enhanced clinical effects.
- Bile acid derivative
- Oral delivery