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.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-03202017-104333 |
| Date | 27 March 2017 |
| Creators | Kavanaugh, Taylor Elizabeth |
| Contributors | Craig Duvall, Ph.D., Todd Giorgio |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-03202017-104333/ |
| Rights | restrictsix, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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