A Peptide-Nanoparticle Delivery System for the Vasculature

球囊血管成形术，有时使用支架，用于扩大周围血管或冠状动脉狭窄的狭窄或阻塞的血管。然而，由于平滑肌细胞的生长和迁移导致血管重塑，患者在干预后经常发生血管再狭窄，即血管再狭窄。这一负面事件可以通过从药物洗脱支架和气囊中逐渐释放两类药物（紫杉烷和Limus）中的任何一类来减轻。然而，这些药物具有普遍的细胞毒性，导致细胞死亡、内皮功能障碍和晚期血栓形成。我们开发了一种毒性较低的嵌合肽来防止血管成形术后的再狭窄。该肽选择性地靶向平滑肌细胞并阻止其迁移，同时使保护性内皮细胞不受伤害。此外，我们还开发了一种纳米颗粒聚合物药物输送系统，用于从血管成形术设备（支架和气球）中逐渐释放嵌合肽。这允许延迟和控制肽的释放，一旦通过设备输送到组织。我们预计该系统将用于治疗支架内冠状动脉再狭窄，并缓解外周动脉狭窄。

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.