The main purpose of this research is to develop an oral delivery device for insulin using a pH responsive hydrogel of poly(methacrylic-g-ethylene glycol), or P(MAA-g-EG).  This nanoporous hydrogel forms a copolymer network that exhibits reversible, pH-dependent swelling behavior.  The network mesh size has been shown to vary between 6 nm at low pH (< 3) and around 20 nm at higher pH (>6).  By modifying the network structure of the hydrogel, the incorporation and release of insulin can be tailored to a greater degree. Understanding the interaction of insulin with this nanoporous hydrogel in vitro and in vivo would provide a great deal of insight into this material's potential for oral protein delivery.

A second aim of this work utilizes the covalent attachment of polyethylene glycol (PEG) to insulin.  This conjugate exhibits a "masking" effect which has been shown to prolong its circulation time in the body.  Additionally, the hydrogen bonds that would exist between a PEG-insulin conjugate and the PEG-containing copolymer have the potential to increase the drug loading efficiency. The PEG-insulin conjugate should also enhance the delivery of the drug based on its mucoadhesion in vivo with the nanoporous glycocalyx of the intestine.