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Evaluation of Absorption Enhancers and Enzyme Inhibitors for the Protection of Human Insulin

A screening study

Shehla A. Uraizee, Andrea M. McPhillips, Adel A. Sakr, and Wolfgang A. Ritschel

College of Pharmacy, University of Cincinnati Medical Center, Cincinnati, OH (USA)

The literature so far points to the fact that proteins and peptides cannot be delivered effectively without the help of adjuvants like absorption enhancers and enzyme inhibitors. Different studies have reported contradictory results regarding the efficacy of these adjuvants in improving the bioavailability of proteins and peptides. This discrepancy in the results could be attributed to the influence of various factors on the performance of these compounds including the type of protein/peptide, concentration of the drug and enzymes, absorption site, and presence of ions. Therefore, proper selection of the adjuvants is critical for the success of the delivery system. In this study, four different enzyme inhibitors (aprotinin, Bowman Birk inhibitor, soybean trypsin inhibitor, sodium taurocholate) were evaluated for their efficacy in protecting the insulin molecule against in vitro degradation by the proteolytic enzymes trypsin and chymotrypsin. The absorption enhancers sodium deoxycholate, disodium ethylenediamine tetraacetate (EDTA) and a polyoxyethylene fatty acid ester (Myrj 45â) have been evaluated using an in situ technique for their ability to improve the absorption of insulin from the ileum. The results of the study indicate that aprotinin and Bowman Birk inhibitor were more effective in protecting insulin against proteolytic degradation up to 2 h in vitro and sodium deoxycholate proved to have better absorption enhancing capabilities even at low concentration in comparison to the other compounds evaluated.

Key words Absorption enhancers · Enzyme inhibitors · Insulin, gastrointestinal absorption, proteolytic degradation · Peptides