W:O:W multiple emulsions of insulin containing a protease
inhibitor and an absorption enhancer: biological activity after
oral administration to normal and diabetic रत्स

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.

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