Electronic Theses and Dissertations

Date of Award

5-1-2026

Document Type

Dissertation

Degree Name

Ph.D. in Chemistry

First Advisor

Eden E.L. Tanner

Second Advisor

Eden E.L. Tanner

Third Advisor

Kensha Clark

School

University of Mississippi

Relational Format

dissertation/thesis

Abstract

Treatment of central nervous systems (CNS) disorders remains a critical challenge in drug delivery. The blood brain barrier (BBB) is an obstacle preventing targeted delivery. Small and large drug molecules are unable to cross the BBB, highly limiting drug therapies. Only invasive techniques and symptom care are currently employed for neurological diseases.

This demands an innovative drug delivery approach to improve efficiency of targeted delivery to the brain, hence polymeric nanoparticles (NPs) being a promising solution. With their advantageous tunability, they can encapsulate various biomolecules and perform specific targeting. Ionic liquids (ILs) have become a novel surface modification of NPs for enhanced targeted delivery due to their tunability, biocompatibility, and biodegradability. This research explores the interactions between the components of the IL NPs themselves and red blood cells.

The influence of IL and polymer in the assembly and degradation of IL NPs is demonstrated using linear dendritic block copolymers, diblock copolymer (DBCP), and copolymers with the IL choline 2-hexenoic acid 1:1. By exposing these polymeric NPs to high salt concentration and acid during the incorporation of IL, it was suggested that both hydrogen bonding and electrostatics are important for “coating” the NPs. However, the polymer system determines the degree in which hydrogen bonding and electrostatics play a role.

Moreover, the thermodynamic and kinetics studies were performed on IL NP systems using 2 DBCPs and 9 different ILs to further elucidate the effect of the polymer and IL in the IL-NP assembly and degradation profile. In addition, it was discovered that even the simple incorporation of glycolic acid into the DBCP changes the stability and the breakdown of the IL NPs.

To enhance targeted delivery to the brain for CNS disorder treatment, this research investigated 3 different ion ratios of one IL as the surface modifiers of PEG-PLGA NPs. In generally, the ratio between cation to anion effects the affinity towards red blood cells with 1:3 showing the better “hitchhiking” and lower toxicity to them. Overall, these findings contribute to the knowledge of IL assembly on polymer-based NPs, further helping develop targeted delivery systems for therapeutic treatment of CNS disorders.

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