Injectable Electrospun Fiber-Hydrogel Composite Delivery System for Prolonged and Nociceptive-Selective Analgesia  

作　　者：Sufang Chen Weifeng Yao Zhendong Ding Jingyi Du Tienan Wang Xue Xiao Linan Zhang Jing Yang Yu Guan Chaojin Chen Yu Tao Mingqiang Li Haixia Wang Ziqing Hei 

机构地区：[1]Department of Anesthesiology and Center for Nanomedicine,The Third Affiliated Hospital,Sun Yat-Sen University,Guangzhou 510630,China [2]Laboratory of Biomaterials and Translational Medicine,The Third Affiliated Hospital,Sun Yat-Sen University,Guangzhou 510630,China [3]Guangdong Provincial Key Laboratory of Liver Disease Research,Guangzhou 510630,China

出　　处：《Advanced Fiber Materials》2024年第5期1428-1445,共18页先进纤维材料（英文）

基　　金：supported by the Joint Funds of National Natural Science Foundation of China(U22A20276);the“Five and five”Project of the Third Affiliated Hospital of Sun Yat-Sen University(2023WW501);the Guangdong Provincial Science and Technology Program(202201020429);the Science and Technology Planning Project of Guangdong Province-Regional Innovation Capacity and Support System Construction(2023B110006);the National Key Research and Development Program of China(2019YFA0111300);the National Natural Science Foundation of China(52373166,22277155,32001012);the Science and Technology Program of Guangzhou(2024A04J6572,202102010217,202102010190);the Guangdong Provincial Pearl River Talents Program(2019QN01Y131);the Science and Technology Planning Project of Guangdong Province of China(2020A0505100035);the Guangdong Basic and Applied Basic Research Foundation(2019A1515011852,2021A1515012318);the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(GZC20233217);the Natural Science Foundation of Guangdong Province for Distinguished Young Scholar(2024B1515020025),and the China Primary Health Care Foundation(2022-003).

摘　　要：Nociceptive-selective analgesia is often preferred over traditional methods,providing effective pain relief with minimum systemic side effects.The quaternary lidocaine derivative QX-314,is a promising local anesthetic for achieving selective analgesia.However,due to its inability to penetrate the cell membrane,its efficacy is limited to intracellular administration.In this study,we aimed to develop an injectable electrospun fiber-hydrogel composite comprising QX-314-loaded poly(ε-caprolactone)electrospun fiber and capsaicin(Cap)-loaded F127 hydrogel(Fiber-QX314/Gel-Cap composite)for long-term and nociceptive-selective analgesia.The sequential and sustained release mechanism of Cap and QX-314 helped remarkably extend the sensory blockade duration up to 44.0 h,and prevent motor blockade.Specifically,our findings indicated that QX-314 can traverse the cell membrane through the transient receptor potential vanilloid 1 channel activated by Cap,thus targeting the intracellular Na+channel receptor to achieve selective analgesia.Moreover,the composite effectively allevi-ated incision pain by suppressing c-Fos expression in the dorsal root ganglion and reducing the activation of glial cells in the dorsal horn of the spinal cord.Consequently,the Fiber-QX314/Gel-Cap composite,designed for exceptional biosafety and sustained selective analgesia,holds great promise as a non-opioid analgesic.

关 键 词：Nociceptive selective analgesia QX-314 TRPV1 Electrospunfiber Injectable hydrogel 

分 类 号：TB383[一般工业技术—材料科学与工程]