# Equipment Supplement - Cold triggered Local Anesthesia for Pain Management

> **NIH NIH R01** · UNIVERSITY OF ALABAMA IN TUSCALOOSA · 2024 · $166,649

## Abstract

PROJECT SUMMARY
There is clinical and scientific interest in developing on-demand local anesthesia, in which local anesthetics can
only be released by an external trigger when and where needed after the first administration. In the past few
years, injectable local anesthetic formulations have been developed that can generate on-demand local
anesthesia triggered by light and ultrasound. However, their clinical application is hindered by shortcomings,
such as basal drug release when the trigger is not applied, a small number of repetitive trigger events for one
injection (usually 4 to 6 times), the trigger event only occurs within a few hours after the injection, potential local
tissue toxicity caused by the external triggers, and expensive preparation procedures. In this research, in order
to overcome these shortcomings, we aim to explore cold triggered local anesthesia. The formulation design
consists of three components: tetrodotoxin (TTX), cold therapy, and thermo-responsive polymersomes/hydrogels.
We hypothesize that TTX is an extremely potent local anesthetic, a small amount can successfully produce local
anesthesia, thereby improving the efficacy of each trigger and increasing the number of trigger events; cold
treatment is a common use of hypothermia in medical therapy, which has the characteristics of low cost, easy
operation, and non-invasiveness; thermo-responsive polymersomes/hydrogels can efficiently encapsulate TTX
at body temperature, but release TTX due to the deconstruction of the polymersomes/hydrogels under cold
treatment. In addition, the polymersomes/hydrogels can stay at the injection site for a long time, acting as a drug
reservoir to achieve long-term effects. Specifically, a large library of polymersomes/hydrogels with various
structures (size and porosity) and properties (structurally stability and shell stiffness) will be fabricated. Such
a library will be a collection of candidates. Iterative screening will be conducted to identify the
polymersomes/hydrogels with the desired in vitro cold triggerable TTX release, enhanced local retention in
tissues, and excellent biocompatibility (cytotoxicity, inflammation, myotoxicity, organ toxicity). Then, the rat
footpad anesthesia model and rat paw incision wound infiltration model will be used to evaluate the in vivo
efficacy and safety of the selected polymersomes/hydrogels in cold triggered local anesthesia.

## Key facts

- **NIH application ID:** 11096165
- **Project number:** 3R01GM144388-03S1
- **Recipient organization:** UNIVERSITY OF ALABAMA IN TUSCALOOSA
- **Principal Investigator:** Chao Zhao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $166,649
- **Award type:** 3
- **Project period:** 2022-09-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11096165

## Citation

> US National Institutes of Health, RePORTER application 11096165, Equipment Supplement - Cold triggered Local Anesthesia for Pain Management (3R01GM144388-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11096165. Licensed CC0.

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