Abstract
A novel class of pH-sensitive complexation hydrogels composed of methacrylic acid and functionalized poly(ethylene glycol) (PEG) tethers, referred to as P(MAA-g-EG) WGA, was investigated as an oral protein delivery system. The PEG tethers were functionalized with wheatgerm agglutinin (WGA), a lectin that can bind to carbohydrates in the intestinal mucosa, to improve residence time of the carrier and absorption of the drug at the delivery site. The ability of P(MAA-g-EG) WGA to improve insulin absorption was observed in two different intestinal epithelial models. In Caco-2 cells P(MAA-g-EG) WGA improved insulin permeability 9-fold as compared with an insulin only solution, which was similar to the improvement by P(MAA-g-EG). P(MAA-g-EG) and P(MAA-g-EG) WGA were also evaluated in a mucus-secreting culture that contained Caco-2 and HT29-MTX cells. Insulin permeability was increased 5-fold in the presence of P(MAA-g-EG) and P(MAA-g-EG) WGA. Overall, it is clear that P(MAA-g-EG) WGA enhances insulin absorption and holds great promise as an oral insulin delivery system.