172d Dynamics of Novel Multifunctional, Intelligent Mucoadhesive Copolymers

Francis M. Marks III and Nicholas A. Peppas. Chemical Engineering, University of Texas at Austin, 1 University Station C0400, Austin, TX 78712-0231

In this research we examine the dynamics of various compositions of intelligent, pH-sensitive and mucoadhesive copolymers of poly(methacrylic acid) (P(MAA) with poly(ethylene glycol) (PEG), at various physiological conditions. Graft copolymer networks of PMAA containing well characterized tethers of PEG or decorated with carbohydrates were prepared using free radical solution UV-polymerization of methacrylic acid (MAA) and monomethacrylate PEG or other functionalized monomers with tetraethyleneglycol dimethacrylate as a crosslinking agent. The copolymers were prepared in different molar ratios and with different tethered graft chain molecular weights. The equilibrium swelling parameters were determined in buffer solutions containing NaCl or CaCl2 at different pH. The calcium binding capacity of the copolymers was determined by measuring the free calcium in solution after incubation of the polymers with CaCl2. Protease inhibition studies were performed by investigating the polymer inhibition of calcium-dependent trypsin. Results suggest that these copolymers are exceptional protein delivery candidates due to their pH-sensitive and controllable swelling behaviour. Additionally, they possess protease inhibitory effects along with their mucoadhesive properties.

This work was in part supported by National Institutes of Health grant No. EB 000246 and the National Science Foundation (DGE-0333080).