# Xylazine and opioid overdose mitigation therapy using decoy receptor biomimetic nanoparticles, NarcoBond platform

> **NIH NIH R43** · CIBOTS, INC. · 2024 · $479,731

## Abstract

The number of opioid deaths has exploded in the last two years. This eruption of overdose deaths is being
wrought by a deadly cocktail of fentanyl and xylazine. Xylazine, also known as “Tranq” or “zombie drug”, is a
powerful veterinary sedative that is incredibly dangerous to people on its own. Xylazine extends the high or
euphoria of opioids, affording greater profits for traffickers. Xylazine elicits these effects by agonism of a2A
adrenergic receptor (a2A) in the spinal cord and brain. Since xylazine is not an opioid, its effects are not reversed
by naloxone (Narcan), the only approved opioid overdose rescue treatment. Narcan’s lifesaving effects stem
from reversal of respiratory depression. Xylazine-fentanyl cocktails have a high potential for fatal overdose since
both substances depress respiratory function and this may account for the surge in deaths. As xylazine antidotes,
existing a2A antagonist are inadequate, suffering from a lack of specificity. A major obstacle to developing a2A
antagonist as xylazine antidotes is extensive functional interplay between the 3 adrenergic receptor a2 subtypes,
causing concern over unexpected side effects. As a result, no approved antidote for xylazine exists. Further,
an agent reversing both opioid and xylazine overdose is an unmet clinical need.
Our Solution: NarcoBondα2/µO - a “nanosponge” containing decoy receptors for fentanyl (mu opioid receptor)
and xylazine (α2A-adrenergic receptor -α2A) will safely corral the drugs in the peripheral blood. As a result, the
drugs are trapped away the central nervous system, thus sparing the patient from the high CNS concentrations
that depress respiration and cause death. This mechanism is distinct from that of countermeasures such as
antagonists like naloxone, which displace and release drug from receptors back into circulation. Further,
NarcoBond’s sequestration mechanism does not trigger unwanted pharmacological antagonism, like that of an
α2A antagonist. A beneficial outgrowth of this mechanism is a broad capability to mitigate against all opioids
& all alpha2 agonists (e.g., Xylazine or its future illicit successors). Given the likelihood that other known
alpha2 agonists may soon appear in illicit drug supplies (as has multiple opiates), this principle is critical. We
envision that first responders will administer naloxone, as is current practice. If clinicians at the hospital observe
xylazine toxicity, they will administer NarcoBond (intravenously) to trap opioids and/or xylazine, fully remedying
life-threatening toxicity. We have already laid part of the groundwork for this approach. Previously, we showed
life-saving effects in rodents with NarcoBondµO, a nanosponge that sequestered opioids in the peripheral blood
from where the opioids were safely cleared. In Aim 1 of this Phase I we will focus on a nanosponge with xylazine
decoy receptors (NarcoBondα2). In Aim2, antagonism of the pharmacological effects xylazine in rodents by
intravenous NarcoBondα2 will ...

## Key facts

- **NIH application ID:** 10920983
- **Project number:** 1R43DA060033-01A1
- **Recipient organization:** CIBOTS, INC.
- **Principal Investigator:** Babak Esmaeli-Azad
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $479,731
- **Award type:** 1
- **Project period:** 2024-05-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10920983

## Citation

> US National Institutes of Health, RePORTER application 10920983, Xylazine and opioid overdose mitigation therapy using decoy receptor biomimetic nanoparticles, NarcoBond platform (1R43DA060033-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10920983. Licensed CC0.

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