Prolongation of nerve block by complexation of local anesthetic with cyclodextrin

背景：神经阻滞广泛用于急性和慢性疼痛的治疗，然而现有的局麻药作用时间短。将左布比卡因与麦芽糖基-β-环糊精复配的环糊精给药系统用于大鼠脊髓和坐骨神经阻滞，观察其持久的局部麻醉效果。方法：观察大鼠鞘内注射左布比卡因与麦芽糖基-β-环糊精复合物后肌肉张力和甩尾潜伏期的变化。此外，我们还观察了在坐骨神经周围皮下给药复合物后本体感觉、运动功能和伤害感觉的变化时间过程。结果：在鞘内阻滞的情况下，所有大鼠在注射局麻药后立即停止尾巴运动。鞘内注射复合左布比卡因显著延长运动阻滞，但不延长感觉阻滞。在坐骨神经阻滞中，所有大鼠在注射左旋布比卡因后均被暂时固定，其复合形式明显延长了麻醉效果，通过本体感觉、运动功能和伤害感觉来评价。此外，左布比卡因制剂测试后，神经阻滞后未观察到组织学和神经学症状。结论：左旋布比卡因与麦芽糖基-β-环糊精络合可安全延长左旋布比卡因对大鼠鞘内阻滞和坐骨神经阻滞的麻醉作用。左旋布比卡因与麦芽糖基-β-环糊精的络合对于设计更安全、长效的左旋布比卡因鞘内和坐骨神经阻滞制剂特别有用。

Background : Neural blockade is widely used for acute and chronic pain management, however existing local anesthetics have a short duration of action. The cyclodextrin-based drug delivery system, consisting of levobupivacaine complexed with maltosyl-β-cyclodextrin, was used in spinal and sciatic nerve blocks in rats, anticipating the prolonged local anesthetic effect.Methods : Muscle tone and tail flick latency were studied over time following intrathecal administration of the complex of levobupivacaine with maltosyl-β-cyclodextrin in rats. In addition, the time course of changes in proprioception, motor function, and nociception following circumferential subcutaneous administration of the complex to the sciatic nerve were also examined.Results : With the intrathecal block, all rats stopped tail movement immediately after injection of the local anesthetics. Intrathecal injection of the complexed levobupivacaine significantly prolonged motor blockade, but not sensory blockade. In sciatic nerve block, all rats were temporarily immobilized after injection of levobupivacaine, its complexed form significantly prolonging the anesthetic effects, as evaluated by proprioception, motor function, and nociception. Furthermore, neither histological nor neurological signs were observed following the nerve blocks with the levobupivacaine preparations tested.Conclusions : The complexation of levobupivacaine with maltosyl-β-cyclodextrin safely prolonged the anesthetic effect of levobupivacaine in both intrathecal and sciatic nerve blocks in rats. The complexation of levobupivacaine with maltosyl-β-cyclodextrin is particularly useful for designing safer and long-acting formulations for levobupivacaine in both intrathecal and sciatic nerve blocks.