STABILIZATION OF INSULIN BY ALKYLMALTOSIDES .B. ORAL ABSORPTION IN-VIVO IN RATS

Enteral absorption of insulin is hampered by instability and self-asso ciation, degradation of insulin by digestive enzymes and by low macrom olecular permeability. Reduction of the influence of these factors thr ough protein stabilization should hypothetically result in increased a bsorption due to a higher concentration gradient of intact insulin acr oss the intestinal mucosal barrier. Insulin in a stabilized form was s hown to be absorbed after duodenal administration in normoglycemic and in diabetic rats. A homologous series of alkylmaltosides were found t o stabilize insulin in solution (Hovgaard et al., 1996). For dodecylma ltoside, only minimal aggregation was observed over extended periods ( 60 days) under agitating conditions. In comparison, regular insulin ag gregated and lost complete biological activity after 8 days. In an int raduodenal rat model, blood glucose levels were depressed to 70% of in itial values and serum insulin concentrations reached 250 mu U/ml. The bioavailability of stabilized dodecylmaltoside insulin was found to b e 0.5-1% based on area under the curve (AUC) determination for plasma insulin levels and decreased AUC (dAUC) for blood glucose level depres sion.