# A novel drug loading method to protect neural cells from oxidative stress induced by a hypoxic/ischemic inflammatory environment

> **NIH NIH R21** · UNIVERSITY OF VIRGINIA · 2020 · $195,613

## Abstract

Project Summary
Reactive oxygen species (ROS) are a major factor in the pathogenesis of ischemic stroke and subsequent
inflammation and neurodegeneration. Our long term goal is to develop biomaterial strategies to attenuate
ROS-mediated damage such as inflammation and preserve sensitive cells, such as those within the brain.
Antioxidant delivery is therapeutically relevant in oxidant-stressed systems and has been shown to markedly
restore myelin in rats after hypoxic-ischemic insult. Delivering such molecules with temporal control is a critical
step in rescuing tissue and promoting regeneration after inflammatory processes mediated by ROS.
Poly(lactic-co-glycolic acid) (PLGA) microparticles can provide a localized, controlled release of encapsulated
drugs. However to date, combining features that support a high loading capacity of small molecule
neurotherapeutics and release greater than a few hours with a delivery strategy that allows a minimally
invasive injection has not been achieved. We have previously encapsulated high loads of the small-molecule
antioxidant drug N-acetylcysteine (NAC) within PLGA microparticles and shown ability of these NAC-loaded
microparticles to protect and rescue oligodendrocyte progenitor cells from hydrogen peroxide-mediated
damage. We now aim to: 1) Modify the encapsulation of drug NAC to achieve high loadings and extended
release profiles of at least 7 days, 2) Protect stem/progenitor cells and primary neurons from oxidative stress
using super-loaded antioxidant particles, and 3) Reduce stroke lesion volumes by injecting our drug delivery
system after temporary ischemia. We hypothesize that controlled release of NAC for 1 week after cerebral
ischemic injury will reduce overall lesion volume and spare neural tissue. These microparticles could be an off-
the-shelf product that prevents further ROS-mediated damage after ischemia and reperfusion. This platform
will yield important insights regarding drug delivery design, such as the loading of small molecule antioxidants
during microparticle formulation, and characterize the specific effects on cells in vitro and in vivo.

## Key facts

- **NIH application ID:** 9928423
- **Project number:** 5R21EB026723-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Kyle J. Lampe
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $195,613
- **Award type:** 5
- **Project period:** 2019-06-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928423

## Citation

> US National Institutes of Health, RePORTER application 9928423, A novel drug loading method to protect neural cells from oxidative stress induced by a hypoxic/ischemic inflammatory environment (5R21EB026723-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9928423. Licensed CC0.

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