(62b) Development of Antioxidant Polymeric Nanoparticles for the Suppression of Doxorubicin Mediated Vascular Chemotoxicity

The maximum tolerable dose of of chemotherapeutics is primarily limited by the toxic side effects caused by non-specific accumulation of drug in healthy tissue. While drug targeting can reduce this nonspecific accumulation, even the best targeting systems still have >80-90% of drug end up outside the tumor. As such, active targeting combined with a method to suppress toxicity in healthy tissue may provide a means of improving treatment outcomes by allowing greater doses of chemotherapeutic to be used. Doxorubicin (DOX) is a chemotherapeutic agent which can generate reactive oxygen species (ROS) that can induce cell death. The hypothesis of this study is that antioxidant polymeric nanoparticles (AoP NPs) delivered concurrently with DOX will reduce apparent DOX toxicity in non-cancerous cells. To evaluate this hypothesis, various antioxidants were evaluated as chemoprotectants against DOX in Human Umbilical Vein Endothelial Cells (HUVEC). Depending on the antioxidant used and its concentration, it was found that it can function as either an antioxidant or pro-oxidant. In the presence of antioxidant, IC50 of DOX was found to be 0.200 &muM with 1mM Trolox, and 1.219 &muM with 1mM vitamin E (liposomes), which were lower and higher, respectively, than that of DOX with no antioxidant, IC50=0.315 &muM.