Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China; Department of Anesthesia, China-Japan Union Hospital of Jilin University, Changchun, 130033, PR China.
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China.
Biomaterials. 2018 Oct;181:378-391. doi: 10.1016/j.biomaterials.2018.07.051. Epub 2018 Jul 27.
Local anesthetics are a class of drugs, which have wide applications in the treatment of acute and chronic pain. However, their analgesic effects only last for a few hours because of their short half-life, which is insufficient for clinical application, especially for long-term surgery or postoperative analgesia. Herein, an injectable hydrogel/microsphere (GEL/MS) composite co-encapsulating bupivacaine (BUP) and dexmedetomidine (DEX) was developed for effective sustained analgesia. The GEL/MS composite appeared as a three-dimensional porous network microstructure and displayed sustained sequential release of DEX and BUP over several days in vitro, without obvious burst release. In this composite, DEX was released from the GEL matrix preferentially, exhibited long-term vasoconstriction effect and improved the local anesthetic concentration at injection site by preventing BUP from diffusing into the blood circulation. BUP was released subsequently from the MS for blockage of the Na channel on nerve cell membranes and provided long-term analgesia. In vivo analgesic effect demonstrated that DEX significantly prolonged the effect of analgesia when synergistically administered with BUP in the GEL/MS composite. Moreover, the GEL/MS composite exhibited good biodegradability and biocompatibility in histological analyses. Taken together, the administration of BUP and DEX in the GEL/MS composite achieved a synergistic effect in prolonging analgesia without causing toxicity, and thus represented a potential strategy for long-acting analgesia therapy.
局部麻醉剂是一类药物，在治疗急性和慢性疼痛方面有广泛的应用。然而，由于其半衰期短，其镇痛效果仅持续几个小时，这对于临床应用来说是不够的，特别是对于长期手术或术后镇痛。在此，开发了一种可注射的水凝胶/微球（GEL/MS）复合材料，共同包埋布比卡因（BUP）和右美托咪定（DEX），以实现有效的持续镇痛。GEL/MS 复合材料呈现出三维多孔网络微结构，并在体外持续数天内显示出 DEX 和 BUP 的顺序释放，没有明显的爆发释放。在这种复合材料中，DEX 优先从 GEL 基质中释放出来，通过阻止 BUP 扩散到血液循环中，表现出长期的血管收缩作用，并提高了注射部位的局部麻醉剂浓度。随后 BUP 从 MS 中释放出来，阻断神经细胞膜上的 Na 通道，提供长期的镇痛效果。体内镇痛效果表明，DEX 与 GEL/MS 复合材料中的 BUP 联合使用时，显著延长了镇痛效果。此外，GEL/MS 复合材料在组织学分析中表现出良好的生物降解性和生物相容性。综上所述，BUP 和 DEX 在 GEL/MS 复合材料中的联合应用在延长镇痛效果方面具有协同作用，而不会引起毒性，因此代表了一种长效镇痛治疗的潜在策略。
