Honors Theses

Date of Award

5-6-2022

Document Type

Undergraduate Thesis

Department

Chemistry and Biochemistry

First Advisor

Eden Tanner

Second Advisor

Nathan Hammer

Third Advisor

Randy Wadkins

Relational Format

Dissertation/Thesis

Abstract

Disorders and diseases of the immune system have become more prevalent in recent decades and can have life-threatening effects on those afflicted. Granulocyte disorders disproportionately affect infants and children, while chronic lymphocytic leukemia is the most common type of leukemia in adults. Unfortunately, current treatments have many drawbacks such as everyday injection, short-lived efficacy, and unknown levels of safety and effectiveness. It is imperative to find more effective treatment options that could allow for easier drug delivery to specific populations of white blood cells (WBCs). Nanoscale medicine shows promising application, but complications remain in reaching the desired target site and potential toxicity to cells. This project aims to identify specific choline-based ionic liquids (ILs) to coat nanoparticles (NPs) in a way that enhances affinity for WBC subpopulations. This will be achieved by synthesizing ILs with varying carboxylic-acid derivative anions and choline bicarbonate in different molar ratios to be assessed for nanoparticle capping ability. The ionic liquid-coated nanoparticles will be mixed ex-vivo with whole mouse blood and screened for monocyte, granulocyte, and lymphocyte affinity via fluorescence activated cell sorting (FACS). The end goal of this project is to identify ILs that show increased affinity for one WBC subpopulation with minimal affinity for remaining blood components, including red blood cells and platelets.

During this project, ILs were correctly synthesized, PLGA NPs were synthesized and capped with said IL, and evaluated for WBC affinity using ex-vivo BAL/C mouse blood work. Over multiple rounds of testing, three ionic liquids were identified to have increased affinity for a specific WBC component and evaluated for potential cytotoxic effects. It was observed that IL-coated PLGA NPs show low toxicity and could serve as a viable option for pharmaceutical development. Future investigation should focus on human blood testing and encapsulating a particular drug within the NP while maintaining the outside IL coating.

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