Therapy of transplantation-induced oxidative injury using polymeric antioxidants

DESCRIPTION (provided by applicant): Ischemia-reperfusion (I/R) injury during renal transplantation surgery is responsible for oxidative stresses which result in immune activation and graft rejection. We are developing an antioxidative therapy that we havealready shown to be highly efficacious in ameliorating damage from oxidative stress in various in vitro models as well as I/R models of kidney, heart, and limb injury. Importantly, no signs of toxicity have been observed in any model. We will, however, undertake a comprehensive safety evaluation as a key component of this grant. The product is a dispersion of polyoxalate-vanillyl alcohol (VA) copolymer particles. The polymer is degraded by hydrogen peroxide (thereby reducing the local concentration of ROS)yielding VA, a potent antioxidant in its own right. We refer to these therapies as Antioxidant Polymer Prodrugs, or APPs . Their polymer chemistry and biology are well understood and indicative of an excellent safety profile. Their site-specific anti