Delivery of Local Anaesthetics by a Self-assembled Supramolecular System Mimicking Their Interactions with a Sodium Channel

Overview

Journal Nat Biomed Eng

Publisher Springer Nature

Specialty Biomedical Engineering

Date 2021 Sep 14

PMID 34518656

Citations 22

Authors

Tianjiao Ji

Yang Li

Xiaoran Deng

Alina Y Rwei

Abraham Offen

Sherwood Hall

Wei Zhang

Chao Zhao

Manisha Mehta

Daniel S Kohane

Affiliations

Soon will be listed here.

Abstract

Site-1 sodium channel blockers (S1SCBs) act as potent local anaesthetics, but they can cause severe systemic toxicity. Delivery systems can be used to reduce the toxicity, but the hydrophilicity of S1SCBs makes their encapsulation challenging. Here, we report a self-assembling delivery system for S1SCBs whose design is inspired by the specific interactions of S1SCBs with two peptide sequences on the sodium channel. Specifically, the peptides were modified with hydrophobic domains so that they could assemble into nanofibres that facilitated specific binding with the S1SCBs tetrodotoxin, saxitoxin and dicarbamoyl saxitoxin. Injection of S1SCB-carrying nanofibres at the sciatic nerves of rats led to prolonged nerve blockade and to reduced systemic toxicity, with benign local-tissue reaction. The strategy of mimicking a molecular binding site via supramolecular interactions may be applicable more broadly to the design of drug delivery systems for receptor-mediated drugs.

Citing Articles

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