title: Analysis of the acute cytotoxic potential of bupivacaine and 50% enantiomeric excess bupivacaine (s75-r25) incorporated into microspheres in rat sciatic nerves.
abstract: OBJECTIVE
  The duration of Local Anesthetic (LA) effects can be expanded by its incorporation into systems of sustained release microspheres. However, the possibility that LA sustained release systems are neurotoxic has not received due attention in literature. The objective of this study was to investigate the effects of pure microspheres of poly(lactic-co-glycolic acid), filled with 50% enantiomeric excess bupivacaine or bupivacaine (BP), as well as the effects of 50% enantiomeric excess bupivacaine in the sciatic nerve of Wistar rats.
  
  
  METHODS
  The rats were allocated into four groups according to the evaluation time (two, four, six, and eight days) and nominated according to the injected solution on the sciatic nerve: Microspheres with 50% Enantiomeric excess Bupivacaine (MEB), Microspheres with Bupivacaine (MB), Pure Microspheres (PM), and 50% Enantiomeric excess Bupivacaine (EB).
  
  
  RESULTS
  In semi-fine histologic sections, no regular homogeneous distribution of collagen fibers in the endoneurium or degenerative changes of axons and myelin sheaths were observed. In ultrathin sections, we found myelinated axons and normal Remak fibers with axoplasm showing homogeneous distribution of neurofilaments and microtubules. Histomorphometric analysis of axons revealed no significant difference between the axon diameters of the studied groups.
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, USA. ptanaka@stanford.edu
authors.forename: Pedro Paulo
authors.initials: PP
authors.lastname: Tanaka
authors.forename: Maria Fernanda
authors.initials: MF
authors.lastname: Torres
authors.forename: Sergio Bernardo
authors.initials: SB
authors.lastname: Tenorio
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008863:Microspheres; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects* / Q000473:pathology; D023382:Toxicity Tests, Acute
chemical_list: D000779:Anesthetics, Local; D002045:Bupivacaine