Intramural delivery of rapamycin with alphavbeta3-targeted paramagnetic nanoparticles inhibits stenosis after balloon injury.

Abstract

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 alpha(v)beta(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) alpha(v)beta(3)-targeted rapamycin nanoparticles, (2) alpha(v)beta(3)-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 alpha(v)beta(3)-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 alpha(v)beta(3)-targeted rapamycin nanoparticles and the 3 control groups.

CONCLUSIONS:

Local intramural delivery of alpha(v)beta(3)-targeted rapamycin nanoparticles inhibited stenosis without delaying endothelial healing after balloon injury.

• Authors: Tillmann Cyrus, Huiying Zhang, John S Allen, Todd A Williams, Grace Hu, Shelton D Caruthers, Samuel A Wickline, Gregory M Lanza
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 28 Issue 5 Pg. 820-6 (May 2008) ISSN: 1524-4636 [Electronic] United States
• PMID: 18292395 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Integrin alphaVbeta3
• Sirolimus

Topics

• Angioplasty, Balloon (adverse effects)
• Animals
• Anti-Bacterial Agents (administration & dosage, pharmacology)
• Constriction, Pathologic (drug therapy, pathology, prevention & control)
• Drug-Eluting Stents
• Endothelium, Vascular (drug effects, pathology)
• Femoral Artery (drug effects, pathology)
• Integrin alphaVbeta3 (administration & dosage)
• Magnetic Resonance Imaging
• Male
• Nanomedicine (methods)
• Nanoparticles (administration & dosage, therapeutic use)
• Rabbits
• Sirolimus (administration & dosage, pharmacology)