Characterization of pH-responsive hydrogels of poly(itaconic acid-g-ethylene glycol) prepared by UV-initiated free radical polymerization as biomaterials for oral delivery of bioactive agents

Effective oral delivery of proteins is impeded by steep pH gradients and proteolytic enzymes in the gastrointestinal tract, as well as low absorption of the proteins into the bloodstream because of their size, charge, or solubility. In this work, pH-responsive complexation hydrogels of poly(itaconic acid) (PIA) with poly(ethylene glycol) (PEG) grafts were synthesized for applications in oral drug delivery. These hydrogels v,,ere expected to be in collapsed configuration at low pH because of hydrogen bonding between PIA carboxyl groups and PEG, and to swell with increasing pH because of charge repulsion between deprotonated carboxylic acid groups. Hydrogels v,,ere prepared by UV-initiated free radical polymerization using tetraethylene glycol as the crosslinking agent and Irgacure (R) 2959 as the initiator. The effect of monomer ratios, crosslinking ratio, and solvent amount Oil the properties of the hydrogels were investigated. The cornposition of the hydrogels was confirmed by Fourier transform infrared spectroscopy. Equilibrium swelling studies ill the pH range of 1.2-7 revealed that the extent of swelling increased with increasing pH Lip to a pH Of about 6, when no further carboxylic acid deprotonation occurred. Studies in Caco-2 colorectal carcinoma cells confirmed the cytocompatibility of these materials at concentrations of tip to 5 mg/mL. (C) 2009 Wiley Periodicals, Inc. J Biomed Mater Res 93A: 175-188, 2010