title: Extended release local anesthetic agents in a postoperative arthritic pain model.
abstract: Local anesthetics play an important role in postoperative pain management in orthopedic joint procedures. The aim of this study was to determine the effect of an intraoperative extra-articular injection of poly(DL-lactic acid co castor oil 3:7), p(DLLA:CO) 3:7 loaded with 15% bupivacaine, for postoperative analgesia following knee arthroplasty. Prolonged release local anesthetic formulation was synthesized by mixing p(DLLA:CO) 3:7 with bupivacaine base. Under anesthesia, the knee joint of Sprague-Dawley rats was exposed, a hole drilled in the femoral trochlea. 0.2 mL of either 15% polymer-bupivacaine formulation or plain bupivacaine (control) was injected locally and compared with a nonsurgery control group. Mechanical hyperalgesia was determined by counting the vocalizations and leg withdrawal after joint squeezing. Behavioral assessments over a day postoperative period revealed a reduction in rearing and ambulation in an open-field apparatus in animals of both experimental groups compared with the nonsurgery control. The vocalizations during the hyperalgesia test increased compared with the control at 24 h. At 48 h, 3.667 ± 0.5138, p = 0.0076 vocalizations were recorded for the plain bupivacaine group versus 1.417 ± 0.5138, p < 0.0001 in the 15% polymer-bupivacaine formulation. Bupivacaine encapsulated in p(DLLA:CO) 3:7 extended the duration of the analgesia compared with plain drug in rats and could represent effective postoperative analgesic in orthopedic joint procedures.
authors.affiliation: Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem, Jerusalem, Israel.
authors.forename: Diana E
authors.initials: DE
authors.lastname: Ickowicz
authors.forename: Ludmila
authors.initials: L
authors.lastname: Golovanevski
authors.forename: Amir
authors.initials: A
authors.lastname: Haze
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Domb
authors.forename: Carolyn F
authors.initials: CF
authors.lastname: Weiniger
mesh_terms: D000777:Anesthetics / Q000737:chemistry* / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000737:chemistry / Q000494:pharmacology; D002368:Castor Oil / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000494:pharmacology*; D004195:Disease Models, Animal; D007719:Knee Joint / Q000187:drug effects; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D010147:Pain Measurement / Q000379:methods; D010149:Postoperative Pain / Q000188:drug therapy*; D011091:Polyesters; D011108:Polymers / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000777:Anesthetics; D000779:Anesthetics, Local; D003692:Delayed-Action Preparations; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D002368:Castor Oil; D002045:Bupivacaine
keywords: biocompatibility; biodegradable polymers; bupivacaine; controlled release; injectables; local anesthetics; polymeric drug carrier