Development of a Potent Antioxidant Delivery Polymer to Target Drug Delivery Sites
Osteoarthritis (OA), is a degenerative joint disease, and is the most common chronic condition of joints affecting over thirty million adults in the US. With OA, cartilage- a firm, rubbery cushion between joints- deteriorates resulting in pain and swelling. OA is closely linked with the overproduction of reactive oxygen species (ROS) which are present in and propagate many diseases related to inflammation including cancers. Currently, there are no cures or preventative measures for OA. Poly(propylene sulfide) (PPS) is a hydrophobic polymer that undergoes a transition to a hydrophilic polymer once oxidized by ROS. PPS can be used for “on-demand” delivery of drugs to relieve ROS-induced inflammation. Due to its hydrophobicity when not oxidized, PPS reacts slowly with ROS such as hydrogen peroxide. Therefore, we propose the synthesis of a more hydrophilic sulfide containing polymer. Using reversible addition fragmentation chain transfer (RAFT) polymerization, poly(pentafluorophenyl) (PFPA), an amine reactive monomer, will be co-polymerized with the small, hydrophilic monomer dimethylacrylamide (DMA) at differing proportions (50:50-90:10) resulting in a library of polymers ranging in hydrophobicity. The DMA-co-PFPA will then be substituted with 2-(methylthio)ethylamine, a small sulfide containing monomer, producing DMA-co-(methylthio)ethylamine. Antioxidant potential of these polymers will be investigated in an aqueous ROS assay to detect hydrogen peroxide. Using a cell line transduced with a hydrogen peroxide sensor, we’ll determine activity of the polymer library in vitro. This proposed work will result in the development of a more potent antioxidant polymer with increased solubility/bioavailabiliy that could target sites of early cartilage degradation and inflammation.