Author ORCID Identifier

http://orcid.org/0000-0003-4093-8979

Year of Publication

2017

Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation

College

Engineering

Department

Chemical and Materials Engineering

First Advisor

Dr. Thomas D. Dziubla

Second Advisor

Dr. Douglass S. Kalika

Abstract

Oxidative stress, which reflects an imbalance between oxidants and endogenous antioxidants, is known to be a cause as well as an effect of health conditions such as cancer, diabetes, Alzheimer’s disease, Parkinson’s disease and ischemia-reperfusion injury. Antioxidants have shown promising results in vitro in controlling oxidative stress. However, years of in vitro studies have failed to translate into effective clinical interventions for controlling oxidative stress in the disease conditions. This has been due to low bioavailability and lower stability of antioxidants. Poly(antioxidant β-amino esters) (PABAE) are a recently-developed class of biodegradable polymeric hydrogels that have shown promise in their ability to control cellular response and reduce oxidative stress while simultaneously enhancing material biocompatibility. In this dissertation, poly(curcumin β-amino ester) (PCBAE) hydrogels were synthesized and tuned using process parameters for the controlled release of curcumin, an antioxidant.

Curcumin was functionalized with acrylate groups to form curcumin multiacrylate (CMA) so that it could be covalently incorporated into a polymer network. Liquid chromatography-mass spectrometry (LCMS) and nuclear magnetic resonance (NMR) were used to identify individual acrylate species present in the resulting multiacrylate mixture. A series of hydrogel networks were formed by polymerization of a commercial diacrylate, polyethylene glycol diacrylate (PEG400DA), and a primary diamine, 4,7,10-trioxa-1,13-tridecanediamine (TTD), in combination with CMA. Aqueous degradation and curcumin release were evaluated, along with the thermomechanical properties of the networks using dynamic mechanical analysis and broadband dielectric spectroscopy. The network properties and curcumin release characteristics were tuned through systematic variations in curcumin composition, amine crosslinker, PEG diacrylate, and ratio of total acrylate to amine. The degradation and resulting antioxidant properties of these biomaterials are closely related to the composition and architecture of the networks established during polymerization. The PCBAEs developed in this study had degradation times ranging from 5 hours to up to 58 hours. Based on these results, one PCBAE variant was selected for the development of tablet formulations for colon specific delivery, and these tablets exhibited a sustained release for 20 hours. Overall, the PCBAE series shows a wide range of degradation and thermomechanical characteristics with potential use in drug delivery, tissue engineering and biomedical applications.

Digital Object Identifier (DOI)

https://doi.org/10.13023/ETD.2017.023

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