on February 21, 2008
Published online before print February 21, 2008, doi: 10.1161/ATVBAHA.107.156281
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Submitted on March 18, 2007
Accepted on January 31, 2008
Intramural Delivery of Rapamycin With 
v
3-targeted Paramagnetic Nanoparticles Inhibits Stenosis After Balloon Injury
Tillmann Cyrus *;
From the Division of Cardiology (T.C., H.Z., J.S.A., T.A.W., G.H., S.A.W., G.M.L.), Washington University School of Medicine, Saint Louis, Mo; and Philips Medical Systems (S.D.C.), Andover, Mass.
* To whom correspondence should be addressed. E-mail: tcyrus{at}im.wustl.edu.
Background—Drug eluting stents prevent vascular restenosis but can delay endothelial healing. A rabbit femoral artery model of stenosis formation after vascular injury was used to study the effect of intramural delivery of 
v
3-integrin–targeted rapamycin nanoparticles on vascular stenosis and endothelial healing responses.
Methods and Results—Femoral arteries of 48 atherosclerotic rabbits underwent balloon stretch injury and were locally treated with either (1) v3-targeted rapamycin nanoparticles, (2) v3-targeted nanoparticles without rapamycin, (3) nontargeted rapamycin nanoparticles, or (4) saline. Intramural binding of integrin-targeted paramagnetic nanoparticles was confirmed with MR molecular imaging (1.5 T). MR angiograms were indistinguishable between targeted and control arteries at baseline, but 2 weeks later they showed qualitatively less luminal plaque in the targeted rapamycin treated segments compared with contralateral control vessels. In a first cohort of 19 animals (38 vessel segments), microscopic morphometric analysis of the rapamycin-treated segments revealed a 52% decrease in the neointima/media ratio (P<0.05) compared to control. No differences (P>0.05) were observed among balloon injured vessel segments treated with v3-targeted nanoparticles without rapamycin, nontargeted nanoparticles with rapamycin, or saline. In a second cohort of 29 animals, endothelial healing followed a parallel pattern over 4 weeks in the vessels treated with v3-targeted rapamycin nanoparticles and the 3 control groups.
Conclusions—Local intramural delivery of v3-targeted rapamycin nanoparticles inhibited stenosis without delaying endothelial healing after balloon injury.
Key words: nanoparticles • MRI • restenosis • rapamycin • drug delivery
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