(196b) Molecular Design And Dynamic Behavior Of Interpolymer Complexing Hydrogels As Carriers For The Oral Delivery Of Therapeutic Proteins

The oral delivery of proteins is a non-invasive alternative to injection as a means for drug administration. Two major challenges are presented by the gastrointestinal tract that must be accounted for in the design of systems for this delivery route. Among these are the presence of proteolytic enzymes, naturally designed to digest proteins, and the epithelial lining of the small intestine, the barrier that the protein must be absorbed through in order to reach the bloodstream. In this work we examine the use of copolymeric hydrogel networks that exhibit pH-dependent swelling behavior due to the formation/dissociation of interpolymer complexes as carriers for oral protein delivery. The protein of interest is trapped inside the gel and protected from enzymatic degradation in gastric conditions and readily released for absorption in intestinal conditions. The investigation evaluates the importance of functional groups and tethered structures on the carrier's capability to serve as an oral delivery agent. The effects of copolymer composition, crosslinking ratio and solvent pH on the swelling behavior of these hydrogels were examined by performing equilibrium and dynamic swelling studies. Additionally, a molecular analysis was performed to examine the functional groups, glass transition temperature and parameters like network mesh size of the various formulations. Loading efficiencies and release kinetics of drug-loaded particles were measured using HPLC.

This material is based upon work supported by grant EB-000246 from the National Institutes of Health and is supported under a National Science Foundation Graduate Research Fellowship to DAC.