McAlvin J Brian, Padera Robert F, Shankarappa Sahadev A, Reznor Gally, Kwon Albert H, Chiang Homer H, Yang Jason, Kohane Daniel S
Department of Medicine, Division of Medicine Critical Care, Harvard Medical School, Boston Children's Hospital, Boston, MA 02115, USA; Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Ave, Building 76-661, Cambridge, MA 02139, USA.
Brigham and Women's Hospital, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Biomaterials. 2014 May;35(15):4557-64. doi: 10.1016/j.biomaterials.2014.02.015. Epub 2014 Mar 6.
Clinical translation of sustained release formulations for local anesthetics has been limited by adverse tissue reaction. Exparel™ (DepoFoam bupivacaine) is a new liposomal local anesthetic formulation whose biocompatibility near nerve tissue is not well characterized. Exparel™ injection caused sciatic nerve blockade in rats lasting 240 min compared to 120 min for 0.5% (w/v) bupivacaine HCl and 210 min for 1.31% (w/v) bupivacaine HCl (same bupivacaine content as Exparel™). On histologic sections four days after injection, median inflammation scores in the Exparel™ group (2.5 of 4) were slightly higher than in groups treated with bupivacaine solutions (score 2). Myotoxicity scores in the Exparel™ group (2.5 of 6) were similar to in the 0.5% (w/v) bupivacaine HCl group (3), but significantly less than in the 1.31% (w/v) bupivacaine HCl group (5). After two weeks, inflammation from Exparel™ (score 2 of 6) was greater than from 0.5% (w/v) bupivacaine HCl (1) and similar to that from 1.31% (w/v) bupivacaine HCl (1). Myotoxicity in all three groups was not statistically significantly different. No neurotoxicity was detected in any group. Tissue reaction to Exparel™ was similar to that of 0.5% (w/v) bupivacaine HCl. Surveillance for local tissue injury will be important during future clinical evaluation.
局部麻醉药缓释制剂的临床应用一直受到不良组织反应的限制。Exparel™（注射用布比卡因脂质体）是一种新型脂质体局部麻醉制剂，其在神经组织附近的生物相容性尚未得到充分表征。与0.5%（w/v）盐酸布比卡因作用120分钟和1.31%（w/v）盐酸布比卡因作用210分钟（与Exparel™布比卡因含量相同）相比，Exparel™注射导致大鼠坐骨神经阻滞持续240分钟。注射后四天的组织学切片显示，Exparel™组的炎症中位数评分（4分中的2.5分）略高于布比卡因溶液治疗组（评分为2分）。Exparel™组的肌毒性评分（6分中的2.5分）与0.5%（w/v）盐酸布比卡因组（3分）相似，但显著低于1.31%（w/v）盐酸布比卡因组（5分）。两周后，Exparel™引起的炎症（6分中的2分）大于0.5%（w/v）盐酸布比卡因（1分），与1.31%（w/v）盐酸布比卡因（1分）相似。三组的肌毒性在统计学上无显著差异。任何组均未检测到神经毒性。Exparel™的组织反应与0.5%（w/v）盐酸布比卡因相似。在未来的临床评估中，监测局部组织损伤将很重要。
