# Dual cavity baskets as nano antidotes for overdose with fentanyl and its derivatives

> **NIH NIH R21** · OHIO STATE UNIVERSITY · 2021 · $231,855

## Abstract

PROJECT SUMMARY/ABSTRACT
The illicit use of synthetic opioids is on the rise, with Ohio being second in the nation per number of overdose
deaths. In this regard, fentanyl is an easily accessible and potent analgesic that has been used in the clinic since
the 1960s. With facile production and derivatization, this class of drugs has been a subject of abuse in which
they are mixed with heroin to lead to overdose. Moreover, carfentanil was in the form of aerosol used in the
terrorist attack in Moscow (2002) resulting in fatalities. With a variety of fentanyl derivatives produced in
clandestine labs (mostly in China) and distributed for illicit use or available to terrorists, there is an immediate
need for developing effective an easily accessible antidote with (a) no or minimal side effects, (b) easy
implementation (injection), (c) rapid onset of action and (d) longer protection. Indeed, naloxone acts as an
effective antagonist to reverse the effect of overdose but due to its rapid clearance it only provides a short-term
protection. As the excess of lipophilic fentanyl distributes in tissues, its slow release into the bloodstream causes
renarcotization. To address the issue as well as side effects, we hereby propose investigating the recognition of
fentanyl and its derivatives using dual-cavity baskets assembled into nanoparticles (i.e., nano-antidotes). Dual-
cavity baskets were developed in our labs to consist of two conjoined and cup-shaped frameworks sharing the
same “floor” with each cup having three amino acids or PEG acids at its terminus. Importantly, polyvalent baskets
trapped two molecules of anticancer anthracyclines in the positive allosteric fashion with ternary complexes
assembling into circa 100 nm nanoparticles. These organic nanoparticles were nontoxic to HeLa cells and
thermodynamically stable in PBS at physiological pH. With baskets being easily accessible and prone to rapid
diversification, we hereby propose a strategy to functionalize them with biocompatible groups (amino acids,
peptides and PEG acids) so that they, in the form of nanoparticles, trap fentanyl and its congeners in the positive
allosteric manner. By forming stable nanoparticle/drug assemblies, the concentration of the drug in the
bloodstream should drop causing a negative gradient in the concentration and therefore its removal from CNS
and tissues. The circulation time of nanoparticles will, via chemical modifications, be tuned to be >24 h to permit
the proposed pharmacokinetic mode of action. To identify basket hosts capable of strongly and allosterically
complexing fentanyl, we will use tools of computational chemistry for selecting candidates for experimental study.
From SARs, we will develop basic rules pertaining the effective recognition of fentanyls in PBS, serum and blood.
Developing a fundamental understanding of the effective recognition of fentanyl and its derivatives with a
modular abiotic host in competitive media will set the stage for studying cooper...

## Key facts

- **NIH application ID:** 10104206
- **Project number:** 1R21DA052444-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Jovica Badjic
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $231,855
- **Award type:** 1
- **Project period:** 2021-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10104206

## Citation

> US National Institutes of Health, RePORTER application 10104206, Dual cavity baskets as nano antidotes for overdose with fentanyl and its derivatives (1R21DA052444-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10104206. Licensed CC0.

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