Oral insulin delivery using P(MAA-g-EG) hydrogels: effects of network morphology on insulin delivery characteristics

Hydrogels of poly(methacrylic acid-g-ethylene glycol) were prepared using different reaction water contents in order to vary the network mesh size, swelling behavior and insulin loading/release kinetics. Gels prepared with greater reaction solvent contents swelled to a greater degree and had a larger network mesh size. All of the hydrogels were able to incorporate insulin and protected it from release in acidic media. At higher pH (7.4), the release rates increased with reaction solvent content. Using a closed loop animal model, all of the insulin loaded formulations produced significant insulin absorption in the upper small intestine combined with hypoglycemic effects. In these studies, bioavailabilities ranged from 4.6% to 7.2% and were dependent on reaction solvent content. (C) 2004 Elsevier B.V. All rights reserved.