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Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Chemistry

Year Degree Awarded

2019

Month Degree Awarded

February

First Advisor

Vincent M. Rotello

Second Advisor

Richard W. Vachet

Third Advisor

Dhandapani Venkataraman

Fourth Advisor

Gregory N. Tew

Subject Categories

Alternative and Complementary Medicine | Bacterial Infections and Mycoses | Biochemistry | Food Chemistry | Medicinal Chemistry and Pharmaceutics | Nanomedicine | Other Immunology and Infectious Disease | Pathogenic Microbiology | Skin and Connective Tissue Diseases | Therapeutics

Abstract

Multidrug-resistant (MDR) bacteria contribute to more than 700,000 annual deaths world-wide. Millions more suffer from limb amputations or face high healthcare treatment costs where prolonged and costly therapeutic regimens are used to counter MDR infections. While there is an international push to develop novel and more powerful antimicrobials to address the impending threat, one particularly interesting approach that has re-emerged are essential oils, phytochemical extracts derived from plant sources. While their antimicrobial activity demonstrates a promising avenue, their stability in aqueous media, limits their practical use in or on mammals. Inspired by the versatility of polymer nanotechnology and the sustainability of traditional medicine, I employed a hybridization approach to improve the stability and subsequently the antimicrobial activity of phytochemical extracts. This approach was accomplished through a crosslinked Nano-emulsification templating strategy, generating a highly robust and reproducible library of potent oil-in-water Nano-assemblies. These assemblies, stabilized using synthetic or natural polymers, demonstrated long-term shelf life, high stability in serum-containing aqueous environments, and most notably, were demonstrated to penetrate highly refractory biofilm infections, eliminating a broad-spectrum of pathogenic bacteria where accumulated resistance towards these materials were not observed during the course of laboratory experiments. Taken together, the technology presented herein, offers key insight into addressing MDR-associated infections with hopes that future platforms can be built from to tackle the rising dangers of MDR infections.

Available for download on Saturday, February 01, 2020

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