title: Multivesicular liposomal bupivacaine at the sciatic nerve.
abstract: 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.
authors.affiliation: 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.
authors.forename: J Brian
authors.initials: JB
authors.lastname: McAlvin
authors.affiliation: Brigham and Women's Hospital, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Padera
authors.affiliation: Amrita Center for Nanosciences and Molecular Medicine, Kochi, Kerala, India.
authors.forename: Sahadev A
authors.initials: SA
authors.lastname: Shankarappa
authors.affiliation: 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.
authors.forename: Gally
authors.initials: G
authors.lastname: Reznor
authors.affiliation: Boston Combined Residency Program in Pediatrics, Boston Children's Hospital, Boston Medical Center, Boston, MA 02115, USA; Brigham and Women's Hospital, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Albert H
authors.initials: AH
authors.lastname: Kwon
authors.affiliation: 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.
authors.forename: Homer H
authors.initials: HH
authors.lastname: Chiang
authors.affiliation: Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Yang
authors.affiliation: 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. Electronic address: daniel.kohane@childrens.harvard.edu.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Kohane
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage*; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage*; D007267:Injections; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects* / Q000648:ultrastructure
chemical_list: D000779:Anesthetics, Local; D008081:Liposomes; D002045:Bupivacaine
keywords: Bupivacaine; DepoFoam; Exparel™; Inflammation; Myotoxicity; Neurotoxicity