# Enzyme-loaded nanoparticles for neonatal neuroprotection

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2021 · $31,129

## Abstract

PROJECT SUMMARY/ABSTRACT
Perinatal asphyxia (PA), where newborn infants suffer from a lack of oxygen and blood flow to the brain, is a
leading cause of morbidity and mortality around the time of birth. PA in term infants, and the resulting
neurodevelopmental sequelae such as intellectual disability, cerebral palsy, epilepsy, and hearing or vision
impairment, result in a huge burden to society. Current therapies such as therapeutic hypothermia have a limited
effect (15% reduction ins death or disability), and are not curative. We propose to develop an effective
neuroprotective treatment using enzyme-loaded nanoparticles in a neonatal model of hypoxia-ischemic (HI) brain
injury. Cellular oxidative stress often begins with the production of superoxide, for example, within the electron
transport chain of dysfunctional mitochondria after HI brain injury. Superoxide is primarily scavenged by
superoxide dismutase (SOD), catalyzing its dismutation anion to hydrogen peroxide,43 which is then converted
to water and oxygen by catalase. The cooperative action of these multiple enzymes is crucial to the successful
clearance of reactive oxygen species. For instance, while SOD overexpression is neuroprotective in a rodent
model of adult stroke, it may exacerbate injury in the neonatal brain due to a relative under-expression of
catalase, resulting in accumulation of hydrogen peroxide. Therefore, precisely-targeted and controlled co-
delivery of cooperative antioxidant enzymes has significant potential for ameliorating oxidative stress in the
setting of neonatal HI brain injury. Therefore, we will investigate the neuroprotective capability of combined
catalase-loaded and SOD-loaded nanoparticles in a neonatal rodent model of term HI brain injury. The first aim
focuses on determining the biodistribution and effective dose of SOD-loaded and catalase-loaded poly(lactic-co-
glycolic)-poly(ethylene glycol) (PLGA-PEG) nanoparticles. The second aim will evaluate the efficacy of a
combined delivery of SOD-loaded and catalase-loaded PLGA-PEG nanoparticles to determine the
neuroprotective effects in newborn rats with HI in comparison to free drug and saline treated controls. This study
is significant because it explores the potential of nanomedicine-based therapy for neuroprotection in a clinically-
relevant model of neonatal HI, with implications for other perinatal brain injuries that share pathological
hallmarks.

## Key facts

- **NIH application ID:** 10391787
- **Project number:** 3R21HD100639-02S1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Elizabeth A Nance
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $31,129
- **Award type:** 3
- **Project period:** 2021-08-03 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10391787

## Citation

> US National Institutes of Health, RePORTER application 10391787, Enzyme-loaded nanoparticles for neonatal neuroprotection (3R21HD100639-02S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10391787. Licensed CC0.

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