Insulin, the most often applied therapeutic protein, possesses many unfavorable features including limited chemical, physical and biological stability, rapid clearance from systemic circulation as well as inherent immunogenicity and antigenicity.Many strategies have been tested to remove or diminish the above mentioned unfavorable properties of insulin. The most important of these is PEG-ylation, that is covalent attachment of methoxypoly(ethylene glycol) (mPEG) to the amino groups in B-chain of insulin molecule, especially to the PheB1 amino group.Research process proves that PEG-ylated insulin while maintaining normal level of biological activity, displays physical stability that is significantly (up to 40 times) higher then native insulin. The PEG-ylated insulin also greatly extends duration of the hypoglycemic effect and shows lack of immunogenicity and antygenicity.For many years, various attempts have been made to utilize insulin in a new delivery system for the formulation of oral insulin. Different strategies are being tested to utilize delivery system for the formulation of PEG-ylated insulin. The main strategy, PEG-ylated insulin used in combination with pH responsive hydrogels, has shown significant promise for oral delivery.

Keywords: insulin, PEG-ylated insulin, mPEG, pH responsive hydrogels.