title: Long acting local anesthetic-polymer formulation to prolong the effect of analgesia.
abstract: Prolonged postoperative analgesia cannot be achieved using single injections of local anesthetic solutions. The study objective was to evaluate the efficacy and toxicity of a new formulation of bupivacaine loaded in an injectable fatty acid based biodegradable polymer poly(sebacic-co-ricinoleic acid) for producing motor and sensory block when injected near the sciatic nerve. Bupivacaine was dissolved in poly(fatty ester-anhydride) paste and tested for drug release in vitro and in vivo after injection in mice. The efficacy and toxicity of the polymer-drug combination was determined by injecting the polymer formulation near the sciatic nerve of mice and measure the sensory and motor nerve blockade for 48 h, while monitoring the animal general health and the injection site. Seventy percent of the incorporated drug was released during 1 week in vitro. Single injection of 10% bupivacaine in the polymer caused motor and sensory block that lasted 30 h. Microscopic examination of the injection sites revealed only mild infiltration in three of eight examined tissues with no pathological findings for internal organs were found. In conclusion the polymer poly(sebacic-co-ricinoleic acid) is a safe carrier for prolonged activity of bupivacaine.
authors.affiliation: School of Pharmacy, Hadassah Hebrew University Medical Schools, Ein Kerem, Jerusalem, POB 12000, Israel.
authors.forename: Ariella
authors.initials: A
authors.lastname: Shikanov
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Domb
authors.forename: Carolyn F
authors.initials: CF
authors.lastname: Weiniger
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage* / Q000494:pharmacology* / Q000633:toxicity; D002626:Chemistry, Pharmaceutical; D003652:Decanoic Acids; D003692:Delayed-Action Preparations; D005079:Excipients; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D011108:Polymers; D051381:Rats; D015203:Reproducibility of Results; D012277:Ricinoleic Acids; D012584:Sciatic Nerve / Q000473:pathology
chemical_list: D000779:Anesthetics, Local; D003652:Decanoic Acids; D003692:Delayed-Action Preparations; D005079:Excipients; C493322:Poly(sebacic acid-co-ricinoleic acid); D011108:Polymers; D012277:Ricinoleic Acids; D002045:Bupivacaine