Open AccessDelivery of local anaesthetics by a self-assembled supramolecular system mimicking their interactions with a sodium channel
Author(s) -
Tianjiao Ji,
Yang Li,
Xiaoran Deng,
Alina Y. Rwei,
Abraham Offen,
Sherwood Hall,
Wei Zhang,
Chao Zhao,
Manisha Mehta,
Daniel S. Kohane
Publication year - 2021
Publication title -
nature biomedical engineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.961
H-Index - 56
ISSN - 2157-846X
DOI - 10.1038/s41551-021-00793-y
Subject(s) - sodium channel , saxitoxin , supramolecular chemistry , chemistry , tetrodotoxin , sodium channel blocker , drug delivery , toxicity , sodium , peptide , pharmacology , biophysics , biochemistry , medicine , molecule , biology , organic chemistry , toxin
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.