Oral insulin delivery systems based on complexation polymer hydrogels

The potential of complexation hydrogels composed of poly(methacrylic acid) grafted with poly(ethylene glycol) (P(MAA-g-EG)) for oral dosage forms of insulin is reviewed. The complexation hydrogels exhibit unique pH-responsive characteristics in which interpolymer complexes are formed and dissociated, respectively, in acidic and neutral/basic environments. The hydrogels are capable of highly incorporating and rapidly releasing insulin in vitro and possess mucoadhesive properties and calcium binding capacities which affect the proteolytic activity of calciumdependent enzymes. The insulin-loaded P(MAA-g-EG) (ILP) successfully enhanced oral insulin absorption without detectable mucosal damage following administration to normal, type 1 and 2 diabetic rats via oral route. Furthermore, ILP significantly suppressed the postprandial rise in blood glucose and showed continuous hypoglycemic effects following multiple oral administration to type 1 and 2 diabetic rats in the presence of foods. These results indicate that the blood glucose levels of diabetics can be effectively controlled by oral ILP administration. Based on these data it is anticipated that the complexation hydrogels will be used for clinical development of oral insulin delivery system, as clinical application of ILP may avoid suffering from injection pain and poor compliance for diabetic patients.