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Title page for ETD etd-03202017-104333
|Type of Document
||Kavanaugh, Taylor Elizabeth
||Antioxidant microspheres as drug delivery vehicles for the prevention of post-traumatic osteoarthritis
||Master of Science
|Craig Duvall, Ph.D.
- Drug Delivery
- Reactive Oxygen Species
- Post-traumatic Osteoarthritis
|Date of Defense
Osteoarthritis (OA) is a disease characterized by degradation of joints with the development of painful inflammation in the surrounding tissues. Post-traumatic osteoarthritis (PTOA) is OA that develops following a traumatic injury to the joint. Currently, there are a limited number of treatments for this disease and many of these only provide temporary, palliative relief. Here, we discuss polymer drug delivery systems that can provide targeted and sustained delivery of imaging and therapeutic agents to OA-affected sites. Polymer based microparticles were investigated as a therapeutic for PTOA. The inherent antioxidant function of poly(propylene sulfide) (PPS) microspheres (MS) was dissected for different reactive oxygen species (ROS), and therapeutic benefits of PPS-MS were explored in mechanically induced PTOA. PPS-MS scavenged hydrogen peroxide (H2O2), hypochlorite, and peroxynitrite but not superoxide in vitro in cell-free and cell based assays. Elevated ROS levels were confirmed in a mouse model of PTOA. In the PTOA model, PPS-MS reduced matrix metalloproteinase activity. These results suggest that local delivery of PPS-MS to site of PTOA reduces articular cartilage destruction. These results motivate further exploration of PPS as a stand-alone, locally-sustained antioxidant therapy and as a material for microsphere-based, sustained local drug delivery to inflamed tissues at risk of ROS damage.
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