# Covalent Naloxone Nanoparticles for Next Generation Fentanyl Countermeasures

> **NIH NIH R21** · ALLEGHENY-SINGER RESEARCH INSTITUTE · 2020 · $210,090

## Abstract

This CounterAct R21 project focuses on early-stage development of a novel nanoparticle-based drug delivery
system for sustained and extended release of the FDA-approved naloxone as a strategy to reduce fatal
overdoses from fentanyl and its analogs. Proposed activities will include optimization of the naloxone-nanoparticle (NLX-NP) formulation and testing its efficacy in pre-clinical models of exposure to fentanyl. The
specter of a fentanyl-based Mass Casualty Incident has been raised in recent years due to the increase
incidence of accidental poisoning due to fentanyl or its analogs. Fentanyl is a potent hydrophobic small
molecule that can cause poisoning upon ingestion of less than 2-3 mg of this compound. The current
countermeasure for a fentanyl poisoning is the administration of multiple doses of a mu opioid receptor
antagonist such as naloxone. Unfortunately, the circulatory half-life of fentanyl is greater than that of the
antidote due to fentanyl’s absorption into adipose tissue, which act as a drug eluting reservoir increasing the
likelihood of re-narcotization. Hence, fentanyl can still act as a poison long after the naloxone has been
metabolized and excreted. To more effectively reverse the lethality of fentanyl and its derivatives, new
antidotes or antidote delivery strategies are required. This R21 project tests the hypothesis that the circulatory
half-life of an antagonist can be increased through the use of a novel drug delivery system consisting of
naloxone covalently bound and incorporated into biodegradable nanoparticles (NLX-NP). The NLX-NP system
allows for the linear sustained release of therapeutic doses of the FDA-approved naloxone. AIM1 will test how
the composition of the nanoparticle-based delivery platform impacts the sustained release of naloxone in rats.
AIM2 will test whether the NLX-NP will reverse or reduce fentanyl-induced pharmacological effects, including
respiratory depression in rats. The NLX-NP will be delivered intramuscularly, which is the route of
administration that best reflects field conditions for delivery of countermeasures to opioids or other chemical
threats.

## Key facts

- **NIH application ID:** 9936632
- **Project number:** 1R21DA050565-01
- **Recipient organization:** ALLEGHENY-SINGER RESEARCH INSTITUTE
- **Principal Investigator:** Saadyah Averick
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $210,090
- **Award type:** 1
- **Project period:** 2020-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9936632

## Citation

> US National Institutes of Health, RePORTER application 9936632, Covalent Naloxone Nanoparticles for Next Generation Fentanyl Countermeasures (1R21DA050565-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9936632. Licensed CC0.

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