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Delivery of local anaesthetics by a self-assembled supramolecular system mimicking their interactions with a sodium channel.
Ji, Tianjiao; Li, Yang; Deng, Xiaoran; Rwei, Alina Y; Offen, Abraham; Hall, Sherwood; Zhang, Wei; Zhao, Chao; Mehta, Manisha; Kohane, Daniel S.
Afiliación
  • Ji T; Laboratory for Biomaterials and Drug Delivery, Department of Anaesthesiology, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
  • Li Y; CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, China.
  • Deng X; Laboratory for Biomaterials and Drug Delivery, Department of Anaesthesiology, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
  • Rwei AY; Laboratory for Biomaterials and Drug Delivery, Department of Anaesthesiology, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
  • Offen A; Laboratory for Biomaterials and Drug Delivery, Department of Anaesthesiology, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
  • Hall S; Laboratory for Biomaterials and Drug Delivery, Department of Anaesthesiology, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
  • Zhang W; US Food and Drug Administration, College Park, MD, USA.
  • Zhao C; Laboratory for Biomaterials and Drug Delivery, Department of Anaesthesiology, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
  • Mehta M; Laboratory for Biomaterials and Drug Delivery, Department of Anaesthesiology, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
  • Kohane DS; Laboratory for Biomaterials and Drug Delivery, Department of Anaesthesiology, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
Nat Biomed Eng ; 5(9): 1099-1109, 2021 09.
Article en En | MEDLINE | ID: mdl-34518656
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anestésicos Locales / Bloqueo Nervioso Límite: Animals Idioma: En Revista: Nat Biomed Eng Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anestésicos Locales / Bloqueo Nervioso Límite: Animals Idioma: En Revista: Nat Biomed Eng Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido