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A Peptide-Nanoparticle Delivery System for the Vasculature

用于脉管系统的肽纳米颗粒输送系统

基本信息

批准号：
570980-2022
负责人：
Bendeck, Michelle
金额：
$ 1.09万
依托单位：
University of Toronto
依托单位国家：
加拿大
项目类别：
Idea to Innovation
财政年份：
2021
资助国家：
加拿大
起止时间：
2021-01-01 至 2022-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=728733
关键词：
Peptide Nanoparticle Delivery System Vasculature

项目摘要

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.

球囊血管成形术，有时使用支架，用于加宽发生在外周血管或冠状动脉狭窄中的狭窄或阻塞的血管。然而，由于平滑肌细胞的生长和迁移引起的血管重塑，再狭窄，即血管的再狭窄，经常发生在介入治疗后的患者中。这种负面事件可以通过从药物洗脱支架和球囊中逐渐释放两类药物（Taxane和Limus）中的任何一种来减轻。然而，这些药物具有导致细胞死亡、内皮功能障碍和晚期血栓形成的一般细胞毒性。我们已经开发了一种毒性较小的嵌合肽，以防止血管成形术后再狭窄。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，我们已经开发了一种纳米颗粒聚合物药物递送系统，其对于从血管成形术装置（支架和球囊）逐渐释放嵌合肽是理想的。这允许一旦经由装置递送至组织，肽的延迟和受控释放。我们预期该系统将用于治疗冠状动脉支架内再狭窄，并缓解外周动脉狭窄。