Characterization of a new class of DNA delivery complexes formed by the local anesthetic bupivacaine.
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.
Pachuk
C J
CJ
Wyeth-Lederle Vaccines, 1 Great Valley Parkway, Malvern, PA 19355, USA. cathydsrna@juno.com
Ciccarelli
R B
RB
Samuel
M
M
Bayer
M E
ME
Troutman
R D
RD
Zurawski
D V
DV
Schauer
J I
JI
Higgins
T J
TJ
Weiner
D B
DB
Sosnoski
D M
DM
Zurawski
V R
VR
Satishchandran
C
C
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
D000779:Anesthetics, Local; D002412:Cations; D008081:Liposomes; D012996:Solutions; D019444:Vaccines, DNA; D014867:Water; D004247:DNA; D020003:1-Octanol; D002045:Bupivacaine