Inhibition of carotid artery neointimal formation with intravenous microbubbles

Because therapeutic gene products such as synthetic antisense oligodeoxynuc leotides (ODN) bind to albumin-coated microbubbles, we sought to determine whether IV perfluorocarbon-exposed sonicated dextrose albumin (PESDA) micro bubbles could target their delivery to the carotid artery following balloon injury. In 5 pigs, the concentration of ODN taken up within the carotid va scular 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. Base d on these results, a chronic model was then developed, in which 21 pigs re ceived either IV ODN-PESDA, ODN alone, or control, following carotid balloo n injury, At 30 days following balloon injury, percent area stenosis was on ly 8 +/- 2% in the ODN-PESDA groups compared to 19 +/- 8% and 28 +/- 3% in the other groups (p < 0.01). IV PESDA mag be a method of noninvasively targ eting the delivery of therapeutic genes. <(c)> 2001 World Federation for Ul trasound in Medicine & Biology.