Approach composed of encapsulation, protease inhibitors and a chelating agent
The pH-sensitive capsule: shields the insulin from hydrolysis in the stomach and ascertains that the protein and other additives within the formulation are contemporaneously released in the small intestines, where the pH is close to neutral.
The protease inhibitors: serve to protect the insulin from degradation by the ubiquitous proteases in the brush border zone of the small intestines.
The chelating agent scavenges calcium: an important cofactor for many proteases, and thereby inhibits intestinal enzyme activities, while also increasing paracellular permeability.