A Peptide-Nanoparticle Delivery System for the Vasculature

球囊血管成形术，有时使用支架，用于扩大发生在外周血管或冠状动脉狭窄处的狭窄或阻塞的血管。然而，血管再狭窄，即血管的再狭窄，往往发生在介入治疗后的患者身上，原因是血管内皮细胞的生长和迁移导致血管重塑。通过从药物洗脱支架和球囊中逐渐释放两种药物(紫杉烷和利莫司)中的任何一种，可以减轻这一负面事件。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。我们已经开发出一种毒性较低的嵌合肽来预防血管成形术后的再狭窄。这种多肽选择性地针对平滑肌细胞并阻止它们的迁移，同时保护内皮细胞不受损害。此外，我们还开发了一种纳米粒子聚合药物输送系统，非常适合从血管成形术设备(支架和球囊)中逐渐释放嵌合肽。这使得一旦通过该装置将多肽输送到组织中，就可以延迟和受控地释放多肽。我们预计，该系统将用于治疗支架内冠状动脉再狭窄，并缓解外周动脉的狭窄。

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.