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 medium-chain triglycerides containing sodium insulin alone or with a protease inhibitor, or with an absorption enhancer, or with a protease inhibitor and an absorption enhancer, were compared to a w/o/w multiple emulsion containing zinc insulin. The release mechanism of all multiple emulsions was the swelling-breakdown phenomenon after dilution of the emulsions under hypo-osmotic conditions. The biological effects after oral administration to normal and diabetics rats showed a larger decrease of glycemia with the multiple emulsions containing sodium insulin than with the multiple emulsion containing zinc insulin. However, there was no significant difference between the hypoglycemic effects induced by the emulsions containing sodium insulin. These results suggest that the aggregation state of insulin molecules might be the major factor responsible for increasing the extent of intestinal insulin absorption. Thus, the nature of the insulin plays a fundamental role and, at the concentration used in this work, the addition of sodium taurocholate 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.