Your browser doesn't support javascript.
loading
Sustained endosomal release of a neurokinin-1 receptor antagonist from nanostars provides long-lasting relief of chronic pain.
Latorre, Rocco; Ramírez-Garcia, Paulina D; Hegron, Alan; Grace, James L; Retamal, Jeffri S; Shenoy, Priyank; Tran, Mai; Aurelio, Luigi; Flynn, Bernard; Poole, Daniel P; Klein-Cloud, Rafael; Jensen, Dane D; Davis, Thomas P; Schmidt, Brian L; Quinn, John F; Whittaker, Michael R; Veldhuis, Nicholas A; Bunnett, Nigel W.
Afiliação
  • Latorre R; Department of Molecular Pathobiology, New York University, New York, 10010, USA; Department of Neuroscience and Physiology, Neuroscience Institute, New York University, New York, 10010, USA.
  • Ramírez-Garcia PD; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
  • Hegron A; Department of Molecular Pathobiology, New York University, New York, 10010, USA; Department of Neuroscience and Physiology, Neuroscience Institute, New York University, New York, 10010, USA.
  • Grace JL; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
  • Retamal JS; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
  • Shenoy P; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
  • Tran M; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
  • Aurelio L; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
  • Flynn B; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
  • Poole DP; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
  • Klein-Cloud R; Department of Molecular Pathobiology, New York University, New York, 10010, USA; Department of Neuroscience and Physiology, Neuroscience Institute, New York University, New York, 10010, USA.
  • Jensen DD; Department of Molecular Pathobiology, New York University, New York, 10010, USA; Bluestone Center for Clinical Research, New York University College of Dentistry, New York, 10010, USA.
  • Davis TP; Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, 4072, Australia.
  • Schmidt BL; Department of Molecular Pathobiology, New York University, New York, 10010, USA; Department of Neuroscience and Physiology, Neuroscience Institute, New York University, New York, 10010, USA; Bluestone Center for Clinical Research, New York University College of Dentistry, New York, 10010, USA.
  • Quinn JF; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
  • Whittaker MR; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia. Electronic address: michael.whittaker@monash.edu.
  • Veldhuis NA; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia. Electronic address: nicholas.veldhuis@monash.edu.
  • Bunnett NW; Department of Molecular Pathobiology, New York University, New York, 10010, USA; Department of Neuroscience and Physiology, Neuroscience Institute, New York University, New York, 10010, USA. Electronic address: nwb2@nyu.edu.
Biomaterials ; 285: 121536, 2022 06.
Article em En | MEDLINE | ID: mdl-35533442
ABSTRACT
Soft polymer nanoparticles designed to disassemble and release an antagonist of the neurokinin 1 receptor (NK1R) in endosomes provide efficacious yet transient relief from chronic pain. These micellar nanoparticles are unstable and rapidly release cargo, which may limit the duration of analgesia. We examined the efficacy of stable star polymer nanostars containing the NK1R antagonist aprepitant-amine for the treatment of chronic pain in mice. Nanostars continually released cargo for 24 h, trafficked through the endosomal system, and disrupted NK1R endosomal signaling. After intrathecal injection, nanostars accumulated in endosomes of spinal neurons. Nanostar-aprepitant reversed mechanical, thermal and cold allodynia and normalized nociceptive behavior more efficaciously than free aprepitant in preclinical models of neuropathic and inflammatory pain. Analgesia was maintained for >10 h. The sustained endosomal delivery of antagonists from slow-release nanostars provides effective and long-lasting reversal of chronic pain.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Dor Crônica / Antagonistas dos Receptores de Neurocinina-1 Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Dor Crônica / Antagonistas dos Receptores de Neurocinina-1 Idioma: En Ano de publicação: 2022 Tipo de documento: Article