Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Chemical and Biochemical Engineering

Supervisor

Dr. Elizabeth Gillies

Abstract

The objective of this research was to develop new polymeric nanomaterials for biomedical applications. It was envisioned that through careful design and synthesis, as well as the study of structure-property relationships, the development of materials with new properties and functions could be achieved. As a starting point, several poly(ester amide)s (PEAs) composed of α-amino acids, diols, and diacids, with varying chemical structures, molecular weights, and polydispersity indices were prepared and their thermal, rheological and mechanical properties were studied. The resulting data will aid in the design and selection of PEAs with optimal properties for targeted applications. Subsequently, a novel PEA-paclitaxel (PTX)-poly(ethylene oxide) conjugate was prepared and assembled into micelles to achieve controlled release of PTX via the hydrolysis of ester linkages. This system was compared with an analogous micellar system into which PTX was physically encapsulated and it was shown that the release of PTX from the covalent system was slower and more sustained. To provide an alternative release mechanism, a functionalized PEA with a photodegradable backbone covalently conjugated to both PTX and PEO was designed and prepared. Upon UV irradiation, micelles, formed from this graft copolymer through self-assembly, disintegrate. This feature accelerates the release of PTX compared with non-irradiated micelles, likely due to the increased exposure and hydrolysis of the ester linkages conjugating the drug to the support, upon micelle disruption. Finally, cross-linked polymer nanoparticles (nanogels) functionalized with Gd(III) chelates were designed, synthesized and characterized as enhanced contrast agents for magnetic resonance imaging (MRI). These nanogels exhibited a T1 relaxivity nearly 6-fold higher than the clinical contrast agent MagnevistÔ. This result is rationalized by the decrease in tumbling and rotational rates as a result of rigidity introduced by the cross-linking. A preliminary in vivo evaluation of this new agent was performed and the agent exhibited good contrast and enhanced circulation in the vasculature relative to MagnevistÔ.


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