Delivery of local anaesthetics by a self-assembled supramolecular system mimicking their interactions with a sodium channel
| Autor: | Wei Zhang, Tianjiao Ji, Abraham Offen, Manisha Mehta, Sherwood Hall, Daniel S. Kohane, Alina Y. Rwei, Chao Zhao, Xiaoran Deng, Yang Li |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
chemistry.chemical_classification
Saxitoxin Sodium channel Biomedical Engineering Supramolecular chemistry Molecular binding Medicine (miscellaneous) Nerve Block Bioengineering Peptide Tetrodotoxin Article Sodium Channels Rats Computer Science Applications Rats Sprague-Dawley chemistry.chemical_compound Sodium channel blocker chemistry Drug delivery Biophysics Animals Anesthetics Local Biotechnology |
| Zdroj: | Nat Biomed Eng |
| ISSN: | 2157-846X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink