# Extracellular vesicles-based drug delivery of antiretroviral regimen to target CNS HIV reservoirs

> **NIH NIH R21** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2021 · $231,000

## Abstract

We propose to design and develop pharmacologically relevant and clinically significant drug delivery strategies
using novel nanocarrier and drug regimens that target CNS HIV reservoirs. Due to the inability of antiretroviral
drugs (ARVs) to cross the blood-brain-barrier (BBB) and ARV-induced neurotoxicity, the current ARV regimens
are incapable of treating HIV-associated CNS dysfunction, including HIV-associated neurocognitive disorders
(HAND). Our drug delivery strategies are designed for enhanced BBB permeability, facilitating drug passage
across the BBB and effectively suppressing the virus in CNS reservoirs, especially in macrophages and
microglia, with minimal/tolerable neurotoxicity. We seek to develop a novel “biological nanoparticle” delivery
system using “extracellular vesicles (EVs)”, which are known to cross the BBB and largely accumulate in
microglia. For drug loading, we will use elvitegravir (EVG), an integrase inhibitor, along with its
pharmacoenhancer, cobicistat (COBI), which are a member of the least toxic class of ARVs and used as first
line of therapy. We will combine EVG with a chemodietary agent, which has been proven to be effective in
treating many CNS diseases and in reducing inflammation and oxidative stress, the hallmark of HIV
pathogenesis. Our central hypothesis is that dual loading of EVG-COBI and chemodietary agent within EVs, will
bypass efflux transporters, cross the BBB, target macrophages and microglia, and deliver EVG and
chemodietary agent to these cells, leading to HIV suppression. We will test the hypothesis by: Aim 1: Developing
EV-drug formulations and determining their efficacy in macrophages and microglia using an in vitro BBB model,
and Aim 2: Determining pharmacokinetic, tissue distribution, and safety profile of EV-drug formulations in an
animal model. We expect to achieve novel nano-formulations of EVG-COBI and chemodietary agent in EVs that
cross the BBB and target macrophages and microglia. Through our future studies, these regimens are eventually
expected to improve HIV treatment outcomes in the CNS and reduce prevalence of HAND and other neurological
disorders.

## Key facts

- **NIH application ID:** 10252514
- **Project number:** 1R21MH125670-01A1
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Santosh Kumar
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $231,000
- **Award type:** 1
- **Project period:** 2021-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10252514

## Citation

> US National Institutes of Health, RePORTER application 10252514, Extracellular vesicles-based drug delivery of antiretroviral regimen to target CNS HIV reservoirs (1R21MH125670-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10252514. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*