title: Characterization of a new class of DNA delivery complexes formed by the local anesthetic bupivacaine.
abstract: Bupivacaine, a local anesthetic and cationic amphiphile, forms stable liposomal-like structures upon direct mixing with plasmid DNA in aqueous solutions. These structures are on the order of 50-70 nm as determined by scanning electron microscopy, and are homogeneous populations as analyzed by density gradient centrifugation. The DNA within these structures is protected from nuclease degradation and UV-induced damage in vitro. Bupivacaine:DNA complexes have a negative zeta potential (surface charge), homogeneous nature, and an ability to rapidly assemble in aqueous solutions. Bupivacaine:DNA complexes, as well as similar complexes of DNA with other local anesthetics, have the potential to be a novel class of DNA delivery agents for gene therapy and DNA vaccines.
authors.affiliation: Wyeth-Lederle Vaccines, 1 Great Valley Parkway, Malvern, PA 19355, USA. cathydsrna@juno.com
authors.forename: C J
authors.initials: CJ
authors.lastname: Pachuk
authors.forename: R B
authors.initials: RB
authors.lastname: Ciccarelli
authors.forename: M
authors.initials: M
authors.lastname: Samuel
authors.forename: M E
authors.initials: ME
authors.lastname: Bayer
authors.forename: R D
authors.initials: RD
authors.lastname: Troutman
authors.forename: D V
authors.initials: DV
authors.lastname: Zurawski
authors.forename: J I
authors.initials: JI
authors.lastname: Schauer
authors.forename: T J
authors.initials: TJ
authors.lastname: Higgins
authors.forename: D B
authors.initials: DB
authors.lastname: Weiner
authors.forename: D M
authors.initials: DM
authors.lastname: Sosnoski
authors.forename: V R
authors.initials: VR
authors.lastname: Zurawski
authors.forename: C
authors.initials: C
authors.lastname: Satishchandran
mesh_terms: D020003:1-Octanol; D000779:Anesthetics, Local / Q000737:chemistry*; D002045:Bupivacaine / Q000737:chemistry*; D002412:Cations; D002499:Centrifugation, Density Gradient; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems; D004587:Electrophoresis, Agar Gel; D015316:Genetic Therapy; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D012996:Solutions; D014162:Transfection; D014466:Ultraviolet Rays; D019444:Vaccines, DNA; D014867:Water
chemical_list: D000779:Anesthetics, Local; D002412:Cations; D008081:Liposomes; D012996:Solutions; D019444:Vaccines, DNA; D014867:Water; D004247:DNA; D020003:1-Octanol; D002045:Bupivacaine