title: Extended duration local anesthetic agent in a rat paw model.
abstract: Encapsulated local anesthetics extend postoperative analgesic effect following site-directed nerve injection; potentially reducing postoperative complications. Our study aim was to investigate efficacy of our improved extended duration formulation - 15% bupivacaine in poly(DL-lactic acid co castor oil) 3:7 synthesized by ring opening polymerization. In vitro, around 70% of bupivacaine was released from the p(DLLA-CO) 3:7 after 10 days. A single injection of the optimal formulation of 15% bupivacaine-polymer or plain (0.5%) bupivacaine (control), was injected via a 22G needle beside the sciatic nerve of Sprague-Dawley rats under anesthesia; followed (in some animals) by a 1cm longitudinal incision through the skin and fascia of the paw area. Behavioral tests for sensory and motor block assessment were done using Hargreave's hot plate score, von Frey filaments and rearing count. The 15% bupivacaine formulation significantly prolonged sensory block duration up to at least 48 h. Following surgery, motor block was observed for 48 h following administration of bupivacaine-polymer formulation and rearing was reduced (returning to baseline after 48 h). No significant differences in mechanical nociceptive response were observed. The optimized bupivacaine-polymer formulation prolonged duration of local anesthesia effect in our animal model up to at least 48 h.
authors.affiliation: Institute for drug research, School of Pharmacy - Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem, Jerusalem, Israel.
authors.forename: D E
authors.initials: DE
authors.lastname: Ickowicz
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Hadassah Hebrew University Medical Center, Israel.
authors.forename: L
authors.initials: L
authors.lastname: Golovanevski
authors.affiliation: Institute for drug research, School of Pharmacy - Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem, Jerusalem, Israel.
authors.forename: A J
authors.initials: AJ
authors.lastname: Domb
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Hadassah Hebrew University Medical Center, Israel; Department of Anesthesia, Stanford University School of Medicine, Stanford, California, USA. Electronic address: carolynfweiniger@gmail.com.
authors.forename: C F
authors.initials: CF
authors.lastname: Weiniger
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002045:Bupivacaine / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002368:Castor Oil / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects*; D010149:Postoperative Pain / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D011091:Polyesters / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects* / Q000503:physiopathology / Q000601:surgery; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000779:Anesthetics, Local; D003692:Delayed-Action Preparations; D011091:Polyesters; C539317:poly(lactic acid-co-castor oil); D002368:Castor Oil; D002045:Bupivacaine
keywords: Bupivacaine; Injectable local anesthetics; Polymer; Prolonged release