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Development of a Novel Biodegradable Drug Polymer for the Modification of Inflammatory Response

The first objective of this thesis was to assess the feasibility of designing a “smart”
degradable polymer that can release anti-inflammatory drugs in response to inflammatory-related enzymes. The drug polymer was synthesized using diisocyanates, poly(caprolactone)diols, and oxaceprol (OC) biomonomers. Biodegradation studies demonstrated that the trimethylhexamethylene diisocyanate-based drug polymer responded to an inflammatory enzyme to release more OC, while a 1, 12-diisocyanatododecane analog demonstrated minimal drug release. The drug delivery response was believed to be a direct function of the molecular structure and distribution of the hard segment.
The second objective of this thesis was to elucidate the anti-inflammatory mechanisms of OC by investigating its effects on cytokine-induced monocytic-cells adhesion
in human umbilical vein endothelial cells (HUVECs) in vitro. Results showed that OC had
no direct effect on the monocyte-endothelium adhesion, suggesting that OC may mediate
inflammation by mechanisms other than those suggested by the literature.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/11148
Date30 July 2008
CreatorsKhor, Sara
ContributorsSanterre, J. Paul
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis
Format7842533 bytes, application/pdf

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