<br>用于延长局部麻醉的高载药量注射水凝胶输送系统,Advanced Science

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用于延长局部麻醉的高载药量注射水凝胶输送系统
Advanced Science ( IF 14.3 ) Pub Date : 2024-03-13 , DOI: 10.1002/advs.202309482
Yongchun Li ₁ , You Chen ₂ , Yifan Xue ₂ , Jinlong Jin ₂ , Yixin Xu ₁ , Weian Zeng ₁ , Jie Liu ₂ , Jingdun Xie ₁

Affiliation

周围神经阻滞可通过减少阿片类药物的消耗来精确控制疼痛并减少手术后的副作用。生物安全性高、含水量高的可注射水凝胶递送系统在局麻药递送方面具有良好的临床应用前景。然而，如何实现水溶性麻醉药物的高载药量和长期控释仍然是一个很大的挑战。在本研究中，异质微球和可注射凝胶基质复合药物递送系统分两步设计。首先，使用微流控芯片和原位碱化制备负载罗哌卡因的异质水凝胶微球（HMS-ROP）。然后用改性羧甲基纤维素 (CMC-ADH) 和氧化透明质酸 (OHA) 制备可注射的自愈水凝胶基质 (Gel)。将HMS-ROP与Gel/DEX相结合，制备出具有体内长期滞留和药物释放功能的局麻药递送系统Gel/HMS-ROP/右美托咪定（DEX）。 HMS-ROP的载药量达到41.1%，体外药物释放时间超过160小时，体内感觉和运动阻滞时间分别为48和36小时。总之，使用核壳微球、DEX和注射凝胶实现了两种麻醉剂的顺序释放和协同镇痛作用，为长效术后疼痛管理提供了一种有前途的策略。

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Injectable Hydrogel Delivery System with High Drug Loading for Prolonging Local Anesthesia

Peripheral nerve block is performed for precise pain control and lesser side effects after surgery by reducing opioid consumption. Injectable hydrogel delivery systems with high biosafety and moisture content have good clinical application prospects for local anesthetic delivery. However, how to achieve high drug loading and long-term controlled release of water-soluble narcotic drugs remains a big challenge. In this study, heterogeneous microspheres and an injectable gel-matrix composite drug delivery system are designed in two steps. First, heterogeneous hydrogel microspheres loaded with ropivacaine (HMS-ROP) are prepared using a microfluidic chip and in situ alkalization. An injectable self-healing hydrogel matrix (Gel) is then prepared from modified carboxymethylcellulose (CMC-ADH) and oxidized hyaluronic acid (OHA). A local anesthetic delivery system, Gel/HMS-ROP/dexmedetomidine (DEX), with long-term retention and drug release in vivo is prepared by combining HMS-ROP and Gel/DEX. The drug loading of HMS-ROP reached 41.1%, with a drug release time of over 160 h in vitro, and sensory and motor blockade times in vivo of 48 and 36 h, respectively. In summary, the sequential release and synergistic analgesic effects of the two anesthetics are realized using core-shell microspheres, DEX, and an injectable gel, providing a promising strategy for long-acting postoperative pain management.

更新日期：2024-03-13

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