Curley J, Castillo J, Hotz J, Uezono M, Hernandez S, Lim J O, Tigner J, Chasin M, Langer R, Berde C
Department of Anesthesia, Children's Hospital, Boston, Massachusetts 02115, USA.
Anesthesiology. 1996 Jun;84(6):1401-10. doi: 10.1097/00000542-199606000-00017.
Biodegradable microspheres are a useful method of drug delivery because they are both injectable and biodegradable, eliminating the need for surgical implantation or removal. Previous work has characterized implantable preparations of local anesthetics in polymer pellets for prolonged regional anesthesia. In this article, the authors characterize injectable suspensions of bupivacaine-polymer microspheres and examine whether they can produce prolonged blockade of the sciatic nerve in rats.
Microspheres were prepared using polylactic-co-glycolic acid polymers loaded with 75% w/w bupivacaine by a solvent evaporation method. Bupivacaine release from microspheres was determined in vitro by ultraviolet spectroscopy and scintillation counting. Sensory and motor blockade of the rat sciatic nerve were assessed in vivo after injection of microsphere suspensions.
Depending on the type of microspheres, the dose, and the additive used, mean duration of sciatic nerve block ranged from 10 h to 5.5 days. Incorporation of 0.05% w/w dexamethasone into the microspheres resulted in significant prolongation of block (up to 13-fold), and only preparations that contained dexamethasone produced blocks lasting beyond 1 day. Bupivacaine was released in a controlled manner in vitro. Dexamethasone does not substantially slow bupivacaine release from microspheres in vitro.
Prolonged percutaneous blockade of peripheral nerves is feasible. The recovery from blockade is complete, and plasma bupivacaine levels are far below the range associated with systemic toxicity. The mechanisms underlying the dexamethasone block-prolonging effect are under investigation.
可生物降解微球是一种有用的药物递送方法，因为它们既可以注射又可生物降解，无需手术植入或取出。先前的研究已对聚合物微丸中局部麻醉剂的可植入制剂进行了表征，以实现长时间的区域麻醉。在本文中，作者对布比卡因 - 聚合物微球的可注射悬浮液进行了表征，并研究它们是否能在大鼠中产生坐骨神经的长时间阻滞。
使用聚乳酸 - 乙醇酸共聚物制备微球，通过溶剂蒸发法负载75% 重量/重量的布比卡因。通过紫外光谱法和闪烁计数法在体外测定微球中布比卡因的释放。注射微球悬浮液后，在体内评估大鼠坐骨神经的感觉和运动阻滞。
根据微球的类型、剂量和所用添加剂的不同，坐骨神经阻滞的平均持续时间为10小时至5.5天。在微球中加入0.05% 重量/重量的地塞米松可显著延长阻滞时间（延长至13倍），只有含有地塞米松的制剂才能产生持续超过1天的阻滞。布比卡因在体外以可控方式释放。地塞米松在体外并不会显著减慢布比卡因从微球中的释放。
外周神经的长时间经皮阻滞是可行的。阻滞恢复完全，血浆布比卡因水平远低于与全身毒性相关的范围。地塞米松延长阻滞作用的潜在机制正在研究中。
