A Peptide-Nanoparticle Delivery System for the Vasculature

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Balloon angioplasty, sometimes using a stent, is used to widen narrowed or obstructed blood vessels that occur in peripheral vascular or coronary stenosis. However, restenosis, the re-narrowing of blood vessels, often occurs in patients following the intervention due to vascular remodeling caused by the growth and migration of smooth muscle cells. This negative event can be mitigated by the gradual release of either of two classes of drugs (Taxane and Limus) from drug-eluting stents and balloons. However, these drugs have general cytotoxicity leading to cell death, endothelial dysfunction and late thrombosis. We have developed a less-toxic chimeric peptide to prevent restenosis following angioplasty. The peptide selectively targets smooth muscle cells and prevents their migration, while leaving the protective endothelial cells unharmed. Additionally, we have developed a nanoparticle polymeric drug delivery system ideal for the gradual release of the chimeric peptide from angioplasty devices (stents and balloons). This allows for delayed and controlled release of the peptide once delivered to the tissue via the devices. We anticipate that this system will be used to treat in-stent restenosis in the coronary artery, and relieve stenosis in peripheral arteries.