Inhibition of carotid artery neointimal formation with intravenous microbubbles.
Because therapeutic gene products such as synthetic antisense oligodeoxynucleotides (ODN) bind to albumin-coated microbubbles, we sought to determine whether IV perfluorocarbon-exposed sonicated dextrose albumin (PESDA) microbubbles could target their delivery to the carotid artery following balloon injury. In 5 pigs, the concentration of ODN taken up within the carotid vascular wall was found to be significantly increased when the IV antisense (ODN) was administered bound to PESDA (ODN-PESDA), and while transcutaneous low-frequency (20 kHz) ultrasound was applied over the carotid artery. Based on these results, a chronic model was then developed, in which 21 pigs received either IV ODN-PESDA, ODN alone, or control, following carotid balloon injury. At 30 days following balloon injury, percent area stenosis was only 8 +/- 2% in the ODN-PESDA groups compared to 19 +/- 8% and 28 +/- 3% in the other groups (p < 0.01). IV PESDA may be a method of noninvasively targeting the delivery of therapeutic genes.
Porter
T R
TR
Internal Medicine Department, Section of Cardiology, University of Nebraska Medical Center, 981165 Nebraska Medical Center, Omaha, NE 68198-1165, USA. trporter@unmc.edu
Hiser
W L
WL
Kricsfeld
D
D
Deligonul
U
U
Xie
F
F
Iversen
P
P
Radio
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S
D000818:Animals; D002339:Carotid Arteries / Q000000981:diagnostic imaging*; D016893:Carotid Stenosis / Q000000981:diagnostic imaging / Q000517:prevention & control*; D002404:Catheterization / Q000009:adverse effects; D005466:Fluorocarbons / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D012709:Serum Albumin / Q000494:pharmacology; D013552:Swine; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000473:pathology; D014463:Ultrasonography / Q000379:methods
D005466:Fluorocarbons; D016376:Oligonucleotides, Antisense; D012709:Serum Albumin