Pain management plays an essential role in medical care. Previous studies showed that pain is a dynamic process involving multiple mechanisms, which inspired the concept of multimodal analgesia. Therefore, a drug delivery system loaded with a single analgesic may be insufficient for pain control. In this study, an implantable thermogel/electrospun fiber (Gel/Fiber) system loaded with bupivacaine hydrochloride (BUP-HCl) and acetaminophen (APAP) was synthesized. In the composite, BUP-HCl was preferentially released from the hydrophilic thermogel to relieve nociceptive pain, followed by the release of APAP in a more sustained manner from hydrophobic fibers to reduce the inflammatory reaction. Pain behavioral study and activation assay of spinal glial cells in the chronic constriction injury (CCI) model demonstrated the superior analgesic efficacy and chronic pain prevention property of the Gel/Fiber system. Furthermore, the composite exhibited satisfactory biocompatibility, as shown by histological and pharmacokinetic analysis. These results indicate that the successful sequential BUP-HCl/APAP release by a Gel/Fiber system alleviates chronic pain with good biocompatibility.Our study may pave the way for the future application of extended-delivery systems.

疼痛管理在医疗保健中起着至关重要的作用。以往的研究表明，疼痛是一个涉及多种机制的动态过程，这启发了多模式镇痛的概念。因此，载有单一镇痛剂的药物输送系统可能不足以控制疼痛。在这项研究中，合成了一种载有盐酸布比卡因 (BUP-HCl) 和对乙酰氨基酚 (APAP) 的可植入热凝胶/电纺纤维 (Gel/Fiber) 系统。在复合材料中，BUP-HCl 优先从亲水性热凝胶中释放以减轻伤害性疼痛，随后以更持久的方式从疏水性纤维中释放 APAP 以减少炎症反应。慢性压迫性损伤 (CCI) 模型中脊髓神经胶质细胞的疼痛行为研究和激活测定证明了凝胶/纤维系统的卓越镇痛功效和慢性疼痛预防特性。此外，如组织学和药代动力学分析所示，复合材料表现出令人满意的生物相容性。这些结果表明，凝胶/纤维系统成功地顺序释放 BUP-HCl/APAP 可减轻慢性疼痛，并具有良好的生物相容性。我们的研究可能为延长递送系统的未来应用铺平道路。