Year of Publication

2013

Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation

College

Engineering

Department

Chemical and Materials Engineering

First Advisor

Dr. Thomas Dziubla

Abstract

There is an undeniable link between oxidative stress, inflammation, and disease. Currently, approaches using antioxidant therapies have been largely unsuccessful due to poor delivery and bioavailability. Responding to these limitations, we have developed classes of polymer and delivery systems that can overcome the challenges of antioxidant and anti-inflammatory therapy. In our initial studies, nanoparticles of poly(trolox), a polymeric form of trolox, were surface-modified with antibodies. This modification allows for specific targeting to endothelial cells, affording controllable and localized protection against oxidative stress. We have shown these targeted nanoparticles bind, internalize, and provide protection against oxidative stress generation and cytotoxicity from iron oxide nanoparticles. In a similar fashion, we have tested the ability of poly(trolox) to prevent rheumatoid arthritis in vivo. Poly(trolox) nanoparticles were encapsulated in a PEGylated polymer to enhance circulation and biocompatibility. These particles were shown to accumulate in inflamed joint tissue, recover natural antioxidant function, suppress protein oxidation, and inhibit inflammatory markers. Lastly, we developed a class of polyphenolic compounds utilizing a non-free radical based reaction chemistry of poly(β-amino esters). The polyphenol apigenin was investigated for its anti-inflammatory properties to inhibit inflammation-mediated tumor cell metastasis. PEGylated nanoparticles that incorporated apigenin poly(β-amino ester) were developed and found to retain their anti-inflammatory efficacy while providing a long term release profile. These inhibited the ability of tumor cells to adhere to inflamed vascular cells. We also have shown that these polymers can suppress markers of inflammation responsible in enhancing tumor cell adhesion.

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