Chronic total occlusions are a common problem in patients with coronary artery disease. The primary barrier to successful percutaneous coronary intervention is inability to cross the lesion with a guidewire. We seek to characterize polymer microspheres as a controlled delivery mechanism for collagenase and VEGF, novel intralesional therapies being investigated to alter CTO structural properties.
Release profiles for protein-loaded PLGA [poly(lactic-co-glycolic acid)] microspheres showed sustained BSA and VEGF release over eight and 48 hours respectively. Polymer degradation products had no impact on endothelial cell growth and protein bioactivity was maintained post-release. In vivo localization of microsphere-released collagenase was not possible due to low concentrations remaining at the site. Histology confirmed microspheres remained in the collagen-dense, proximal 15 mm of the lesion, likely altering the structural integrity of the plaque.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/25583 |
| Date | 31 December 2010 |
| Creators | Fraser, Ashley |
| Contributors | Strauss, Bradley |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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