Novel Bioadhesive Complexation Networks for Oral Protein Drug Delivery

Copolymer networks of poly(methacrylic acid) grafted with poly(ethylene glycol), which exhibit pH-sensitive swelling behavior due to the reversible formation/dissociation of interpolymer complexes, are investigated as potential carriers for protein drugs. The ability of these gels to serve as oral carriers for proteins was examined. The release kinetics of insulin from complexed and uncomplexed gels was studied. The rate of insulin release from the gels was strongly dependent on the pH of the environmental fluid and the copolymer composition. Because of interpolymer compelxation, the release rate of the drug in acidic fluids simulating the conditions of the stomach was an order of magnitude greater than the release rate in fluids simulating that of the upper small intestine. Additionally, these materials exhibit favorable bioadhesive characteristics for oral protein delivery. The mucoadhesive interactions were significantly stronger between the highly swollen, uncomplexed gels and the mucosa.