Master of Science
Engineering in Medicine
Hydrogels are 3-dimensional crosslinked polymer networks that can absorb significant amounts of water. The physical properties associated with hydrogels affords them resemblance to biological tissues making them good candidates for biomedical applications. Many pharmaceuticals, specifically non-steroidal anti-inflammatory drugs (NSAIDs), have poor aqueous solubility, which limits their bioavailability and efficacy. People suffering from chronic osteoarthritis (OA) are required to frequently take large doses to mitigate pain, which can lead to serious side effects. Hydrogels are good strategies to deliver NSAIDs via articular injection because they can form solid gels in situ. This thesis describes the synthesis, formulation, mechanical testing, in vitro and in vivo trials of triblock copolymer (PCLA-PEG-PCLA) hydrogels. We observed that drug-loading can have negatively impact the gelation behaviour. Block lengths were tuned, and we found that using PEG2000 was better to maintain gelation integrity upon drug-loading. We further looked to improve mechanical properties by investigating a redox initiated crosslinking system with methacrylated end-caps. These gels were able to maintain or improve gelation upon loading of various drugs. The optimized chemically crosslinked formulation was able to provide a sustained release of celecoxib in horses for up to 32 d. These results are significant because currently, there is no curative or pain relief option for OA patients beyond 16 d while limiting systemic drug concentration.
Prince, Andy, "Development of in situ Forming Hydrogels for Intra-articular Drug Delivery" (2019). Electronic Thesis and Dissertation Repository. 6077.
Biomaterials Commons, Diseases Commons, Inorganic Chemistry Commons, Materials Chemistry Commons, Molecular, Cellular, and Tissue Engineering Commons, Organic Chemicals Commons, Organic Chemistry Commons, Polymer Chemistry Commons