Prolongation of nerve block by complexation of local anesthetic with cyclodextrin

背景：神经阻滞广泛用于急慢性疼痛的治疗，但现有的局麻药作用时间较短。将左旋布比卡因与麦芽糖基-β-环糊精复合构成的环糊精给药系统应用于大鼠脊髓和坐骨神经阻滞，以期获得较长的局麻药效应。方法：鞘内注射左旋布比卡因-麦芽糖基-β-环糊精复合体，观察肌张力和甩尾潜伏期的变化。结果：鞘内阻滞后，所有大鼠在注射局麻药后立即停止尾部运动。鞘内注射复合左旋布比卡因可显著延长运动阻滞时间，但不能延长感觉阻滞时间。在坐骨神经阻滞中，所有大鼠在注射左旋布比卡因后都被暂时固定，其复合体明显延长了麻醉效果，通过本体感觉、运动功能和伤害性感觉来评价。结论：左旋布比卡因与麦芽糖基-β-环糊精的络合作用安全地延长了左旋布比卡因在鞘内和坐骨神经阻滞中的麻醉效果。左旋布比卡因与麦芽糖基-β-环糊精的络合对于设计鞘内和坐骨神经阻滞中左旋布比卡因更安全和长效的制剂特别有用。

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.