Synthesis and Safety Evaluation of Nanoparticles Used for Blood Cell Hitchhiking for HIV Antiviral Drug Delivery

Author

Jordan A. GillFollow

Date of Award

Spring 5-1-2025

Document Type

Undergraduate Thesis

Department

Biology

First Advisor

Eden Tanner

Second Advisor

Susan Pedigo

Third Advisor

Saumen Chakraborty

Relational Format

Disertation/Thesis

Abstract

Due the challenge of passing the blood brain barrier (BBB) in drug delivery efficiency among combination antiretroviral therapies for HIV-1, Red Blood Cell (RBC) Hitchhiking using Ionic Liquid (IL) coated Nanoparticles (NPs) has emerged as a promising strategy to enhance targeted delivery and therapeutic outcomes. Choline-based ILs are proposed to not only improve the stability and attachment of nanoparticles to RBC membranes but also to mitigate the shear forces nanoparticle encounter in circulation. To evaluate the biocompatibility and stability of this system, RBCs were subjected to osmotic, mechanical, and oxidative stress assays. Osmotic stress was assessed by exposing RBCs to varying concentrations of sodium chloride (NaCl), with hemolysis (percent lysis) measured as the output. Mechanical stress was tested by applying shear forces and turbulence, simulating circulatory strain, followed by analysis of RBC lysis. Oxidative stress was induced by exposing RBCs to different levels of reactive oxygen species (ROS), evaluating both oxygen-carrying capacity and overall cell health. These assays help confirm the robustness of RBCs under stress conditions, ensuring their viability as drug delivery vehicles while establishing b baseline metrics for the success of IL-coated NP loading. In this study, three antiretroviral drugs- Lamivudine, Abacavir, and Dolutegravir- were proposed for loading onto IL-capped, NP- coated RBCs. Dolutegravir (DOL) functions as an integrase strand transfer inhibitor (INSTI) while Abacavir (ABC) and Lamivudine (LAM) are both nucleoside reverse transcriptase inhibitors (NRTIs), working through similar mechanisms to block viral replication. These drugs are known for their synergistic effects in combination therapy, minimal drug-drug interactions, and suitability for simplified dosing regimens. To quantify drug loading and confirm successful encapsulation, High Performance Liquid Chromatography (HPLC) was used to generate calibration curves for each drug. This allowed for accurate measurement of drug concentration on the nanoparticles and could be used in further studies to find encapsulation of each specific drug at different concentrations. Dynamic Light Scattering (DLS) was used to characterize the nanoparticles, confirming appropriate size distribution and zeta potential values to validate successful synthesis, IL capping, and possible drug encapsulation.

The goal of this study is to develop and evaluate the Red Blood Cell (RBC) hitchhiking drug delivery system using choline-based ionic liquid (IL)-coated nanoparticles for the targeted delivery of combination antiretroviral therapies using Lamivudine, Abacavir, and Dolutegravir, and to assess the stability, safety, and drug loading efficiency of the system under osmotic, mechanical and oxidative stress conditions.

Recommended Citation

Gill, Jordan A., "Synthesis and Safety Evaluation of Nanoparticles Used for Blood Cell Hitchhiking for HIV Antiviral Drug Delivery" (2025). Honors Theses. 3358.
https://egrove.olemiss.edu/hon_thesis/3358