Gregory Rutkowski1, John H Brekke1, Sarah Philen2, and Aderinsola Gilbert1. (1) Chemical Engineering, University of Minnesota, Duluth, 176 Engineering Bldg, 1303 Ordean Court, Duluth, MN 55804, (2) Biology, University of Minnesota, Duluth, 215 Engineering Bldg, 1303 Ordean Court, Duluth, MN 55804
In the presence of water, hyaluronic acid (MW = 900k) will form a polyelectrolytic complex (PEC) with chitosan (MW = 600k) to create a network of nanoscale fibers. These fibers impart viscoelastic properties to the hydrogel while providing an excellent substrate for cell adhesion and growth. In conjuction with this, a paclitaxel-hyalurinic acid conjugate has been synthesized for incorporation within the hydrogel. The conjugate enhances the solubility of the paclitaxel while providing an additional mechanism for delivery via the CD44 receptor pathway. During the complexation process, the conjugate may either become entrapped between the PEC fibers or interact directly with the chitosan.
We hypothesize that this system will provide multiple mechanisms for drug delivery. First, free conjugate will diffuse out of the material into the surrounding tissue. As the material degrades, the conjugate will be released for long term delivery. Finally, since low molecular weight hyaluronic acid acts as a chemoattractant for many carcinomas, these cells will be directed into the material from the release of the degradation products where they will encounter the residual cytotoxic agents.