W O/W MULTIPLE EMULSIONS OF INSULIN CONTAINING A PROTEASE INHIBITOR AND AN ABSORPTION ENHANCER - BIOLOGICAL-ACTIVITY AFTER ORAL-ADMINISTRATION TO NORMAL AND DIABETIC RATS/

In this work, the biological effects of w/o/w multiple emulsions of me dium-chain triglycerides containing sodium insulin alone or with a pro tease inhibitor, or with an absorption enhancer, or with a protease in hibitor and an absorption enhancer, were compared to a w/o/w multiple emulsion containing zinc insulin. The release mechanism of all multipl e emulsions was the swelling-breakdown phenomenon after dilution of th e emulsions under hypo-osmotic conditions. The biological effects afte r oral administration to normal and diabetics rats showed a larger dec rease of glycemia with the multiple emulsions containing sodium insuli n than with the multiple emulsion containing zinc insulin. However, th ere was no significant difference between the hypoglycemic effects ind uced by the emulsions containing sodium insulin. These results suggest that the aggregation state of insulin molecules might be the major fa ctor responsible for increasing the extent of intestinal insulin absor ption. Thus, the nature of the insulin plays a fundamental role and, a t the concentration used in this work, the addition of sodium taurocho late was not able to modify its aggregation state in aqueous solution, as confirmed by circular dichroism studies. (C) 1998 Elsevier Science B.V. All rights reserved.