内体
消炎药
敌手
慢性疼痛
药理学
速激肽受体1
受体拮抗剂
神经病理性疼痛
伤害
材料科学
医学
P物质
麻醉
受体
神经肽
内科学
精神科
呕吐
止吐药
作者
Rocco Latorre,Paulina Ramírez-Garcia,Alan Hégron,James L. Grace,Jeffri S. Retamal,Priyank Shenoy,Mai Tran,Luigi Aurelio,Bernard L. Flynn,Daniel P. Poole,Rafael Klein-Cloud,Dane D. Jensen,Thomas P. Davis,Brian L. Schmidt,John F. Quinn,Michael R. Whittaker,Nicholas A. Veldhuis,Nigel W. Bunnett
出处
期刊:Biomaterials
[Elsevier]
日期:2022-06-01
卷期号:285: 121536-121536
被引量:13
标识
DOI:10.1016/j.biomaterials.2022.121536
摘要
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.
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