Electronic Theses and Dissertations

Date of Award

1-1-2025

Document Type

Dissertation

Degree Name

Ph.D. in Chemistry

First Advisor

Eden E. L. Tanner

Second Advisor

Susan D. Pedigo

Third Advisor

Nathan I. Hammer

School

University of Mississippi

Relational Format

dissertation/thesis

Abstract

Septicemia is the worldwide leading cause of death, surpassing even cancer and cardiovascular disease, with a mortality rate of 30-50%. Bloodborne infections are commonly caused by a mixture of opportunistic gram-positive and gram-negative bacteria entering the bloodstream, which leads to a cascading immune response and deterioration of tissues and organs. The effectiveness of current sepsis treatments with broad-spectrum antibiotics is dwindling with microbes ever-evolving towards greater multi-drug resistance. Therefore, development of replacement therapies is a priority. Ionic liquids (ILs) possess beneficial properties including being extremely tunable, which means their chemical structures can be altered to manipulate interactions with biomaterials or bacteria. Ammonium carboxylic acid ILs, in particular, appear to be opportune bactericidal agents by attaching their lipophilic anion layer to the bacterial membrane, causing disruption, while causing minimal damage to human cells. Although the ILs are performing the heavy lifting in terms of antibacterial activity, they require a vehicle to be delivered to specific targets within the body. Coating ILs onto the surface of poly(lactic-co-glycolic acid) (PLGA) polymeric nanoparticles (NPs) allows for specialized activation of the innate immune response by tuning serum protein adsorption and thus potentially “cloaking” nanomaterials to elongate circulation times upon intravenous injection. The utilization of IL-NPs to selectively target and capture bacterial cells in whole blood could alleviate infection without the need for pathogen identification or risk of tissue damage and organ failure caused by endotoxin release with in vivo bactericide. Reliance on regulation of the inflammatory response is essential for removal of captured microbes and thus blood purification.

Available for download on Friday, July 30, 2027

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