Abstract
Antiretroviral drug therapy (ART) has significantly reduced HIV-1 morbidity and improved life expectancy. However, drug expenses, treatment failures, dosing complexities, and limited global access has prevented the full utility of ART. Previous work has shown that nanoparticles (NPs) coated with a single antiretroviral drug promote sustained local drug release and deliver drug concentrations exceeding what is reported to be necessary to inhibit HIV-1 strain replication. This project is designed to investigate the ability of nanoparticle drug carrier systems to deliver a combination of three clinically relevant ART drugs to immune cells targeted by HIV-1. Initial experiments involve the development of cellular assays to test uninfected immune cell viability and function following ART-NP loading. MTT assays and cell counts are used to assess cell viability, HPLC was to assess the amount of drug in cells and media over time, and immunocytochemistry to observe cellular structure and ART-NP localization. Pharmacodynamics of ART-NPs will be investigated using a hollow-fiber drug dosing system. The hollow-fiber drug dosing system is a culture model system comprised of hollow fiber bioreactors that simulate a central and peripheral compartment of the central nervous system. Using this hollow-fiber drug dosing system, the ability of ART-NP to diffuse across a membrane and be phagocytosed by immune cells will be assessed. Future work will utilize the bioreactor data to determine the effectiveness ART-NP to induce rapid and sustained attenuation of viral replication in HIV-1 infected immune cells. Information gathered from this project will help to determine whether nanoparticle drug carrier systems will help to overcome pharmacokinetic obstacles of ART and provide successful universal therapy for HIV-1 infected individuals world wide.