# Enzyme-loaded nanoparticles for neonatal neuroprotection

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2020 · $183,558

## 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:** 9871310
- **Project number:** 1R21HD100639-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Elizabeth A Nance
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $183,558
- **Award type:** 1
- **Project period:** 2020-06-16 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9871310

## Citation

> US National Institutes of Health, RePORTER application 9871310, Enzyme-loaded nanoparticles for neonatal neuroprotection (1R21HD100639-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9871310. Licensed CC0.

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