# Polymer-tetrodotoxin conjugates for prolonged duration local anesthesia

> **NIH NIH R15** · UNIVERSITY OF ALABAMA IN TUSCALOOSA · 2020 · $429,515

## Abstract

It has been a long-standing goal to develop local anesthetic formulations producing prolonged duration local
anesthesia (PDLA) with minimal side effects. Tetrodotoxin (TTX), a site 1 sodium-channel blocker, which blocks
the sodium channel at site 1 on the cell surface, is a naturally occurring compound with extremely potent local
anesthetic properties. Besides, TTX does not cause myo- or neurotoxicity. However, the principal reason that
TTX has not achieved clinical use despite its great potency is concern over its associated systemic toxicity. The
TTX overdose causes neural blockade and muscular weakness resulting in diaphragmatic paralysis leading to
respiratory arrest and death. The primary objective of this research is to use the drug controlled release
technology to address the limitations imposed by the toxicity of TTX and to provide PDLA lasting 2-4 weeks from
a single injection. To achieve this goal, we propose to 1) covalently conjugate TTX onto polymer backbones
through ester bonds, hydrolysis of which can achieve the slow release of TTX; 2) make the polymer backbone
to be liquid, viscous and hydrophobic, where the enhanced local material retention can be accomplished. Once
we fabricated the formulation, the duration of nerve blockade and systemic toxicity will be assessed using the
rat sciatic nerve block model and neurobehavioral testing. Pharmacokinetics (PK)-pharmacodynamics (PD)
models of the sustained-release TTX and the tissue toxicity following the PDLA will also be investigated. If
successful, this research could have a substantial clinical impact. Sustained-release formulations of TTX would
increase the safety margin of TTX, improve patient compliance due to less frequent anesthetic administration,
reduce and possibly eliminate the need for opioids in pain treatment to avoid complications and to lessen the
risk of addiction.

## Key facts

- **NIH application ID:** 10046799
- **Project number:** 1R15GM139193-01
- **Recipient organization:** UNIVERSITY OF ALABAMA IN TUSCALOOSA
- **Principal Investigator:** Chao Zhao
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $429,515
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10046799

## Citation

> US National Institutes of Health, RePORTER application 10046799, Polymer-tetrodotoxin conjugates for prolonged duration local anesthesia (1R15GM139193-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10046799. Licensed CC0.

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