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To address those issues, we developed liposomal formulations of saxitoxin (STX), a compound with ultrapotent local anesthetic properties but little or no cytotoxicity. In vitro, the release of bupivacaine and STX from liposomes depended on the lipid composition and on whether dexamethasone was incorporated. In cell culture, bupivacaine, but not STX, was myotoxic (to C2C12 cells) and neurotoxic (to PC12 cells) in a concentration- and time-dependent manner. Liposomal formulations containing combinations of the above compounds produced sciatic nerve blockade lasting up to 7.5 days (with STX + dexamethasone liposomes) in male Sprague\u2013Dawley rats. Systemic toxicity only occurred where high loadings of dexamethasone increased the release of liposomal STX. Mild myotoxicity was only seen in formulations containing bupivacaine. There was no nerve injury on Epon-embedded sections, and these liposomes did not up-regulate the expression of 4 genes associated with nerve injury in the dorsal root ganglia. These results suggest that controlled release of STX and similar compounds can provide very prolonged nerve blocks with minimal systemic and local toxicity.<\/jats:p>","DOI":"10.1073\/pnas.0900598106","type":"journal-article","created":{"date-parts":[[2009,4,13]],"date-time":"2009-04-13T20:45:48Z","timestamp":1239655548000},"page":"7125-7130","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":134,"title":["Prolonged duration local anesthesia with minimal toxicity"],"prefix":"10.1073","volume":"106","author":[{"given":"Hila","family":"Epstein-Barash","sequence":"first","affiliation":[{"name":"Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115;"},{"name":"Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Shichor","sequence":"additional","affiliation":[{"name":"Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115;"},{"name":"Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert H.","family":"Kwon","sequence":"additional","affiliation":[{"name":"Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherwood","family":"Hall","sequence":"additional","affiliation":[{"name":"Chemical Contaminants Branch HFS-716, Division of Bioanalytical Chemistry Office of Regulatory Science, U.S. Food and Drug Administration Center for Food Safety and Applied Nutrition, 5100 Paint Branch Parkway, College Park, MD 20740; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Lawlor","sequence":"additional","affiliation":[{"name":"Program in Genomics, Department of Medicine, Children's Hospital Boston, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Langer","sequence":"additional","affiliation":[{"name":"Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S.","family":"Kohane","sequence":"additional","affiliation":[{"name":"Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,4,28]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199810000-00022"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(03)00049-6"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e31816c8a48"},{"key":"e_1_3_4_4_2","first-page":"304","article-title":"Local myotoxicity of bupivacaine in rabbits after continuous supraclavicular brachial plexus block","volume":"18","author":"Pere P","year":"1993","unstructured":"P Pere, H Watanabe, M Pitkanen, T Wahlstrom, PH Rosenberg, Local myotoxicity of bupivacaine in rabbits after continuous supraclavicular brachial plexus block. 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