Ng Xu Wen, Huang Yingying, Liu Kerh Lin, Lim Soon Ghim, Chen Horng Haur, Burnett John C, Freddy Boey Yin Chiang, Venkatraman Subbu S
School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore.
Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905.
J Pharm Sci. 2014 Nov;103(11):3631-3640. doi: 10.1002/jps.24165. Epub 2014 Sep 15.
Despite the success that drug-eluting stents (DESs) have achieved for minimizing in-stent restenosis (ISR), the antirestenotic agents used in DES have been implicated in delayed endothelial healing and impairment of endothelial functions. Cenderitide (CD-NP) is a novel antiproliferation chimeric peptide of semiendothelial origin; thus, this paper aims to demonstrate the selectivity aspect of this new peptide via in vitro evaluation on key players in ISR-smooth muscle cells (SMCs) and endothelial cells. The microbicinchoninic acid protein assay was used to investigate the CD-NP release from films and stents. Cenderitide-containing films blended with poly(ethylene glycol) and its copolymer exhibited higher release kinetics compared with neat poly(ε-caprolactone) (PCL) formulation. Cenderitide-eluting stents (CES) was produced by coating bare metallic stents with CD-NP entrapped PCL using an ultrasonic spray coater. The investigation of CD-NP on in vitro cells revealed that CD-NP inhibits human coronary smooth muscle cells (HCaSMCs) proliferation but exhibits no effects on human umbilical vein endothelial cells (HUVECs) proliferation. Moreover, CD-NP released up to 7 days displayed inhibitory effects on SMCs proliferation. The CES produced in this work shows that the released CD-NP inhibits HCaSMCs proliferation but did not hamper HUVECs proliferation in vitro, suggesting that it has potential to reduce ISR without retarding the endothelialization healing in vivo.
尽管药物洗脱支架(DESs)在使支架内再狭窄(ISR)最小化方面取得了成功,但DES中使用的抗再狭窄药物与内皮愈合延迟和内皮功能受损有关。Cenderitide(CD-NP)是一种新型的半内皮来源的抗增殖嵌合肽;因此,本文旨在通过对ISR关键参与者——平滑肌细胞(SMCs)和内皮细胞进行体外评估,来证明这种新肽的选择性。采用微生物辛可宁酸蛋白测定法研究CD-NP从薄膜和支架中的释放情况。与纯聚(ε-己内酯)(PCL)制剂相比,与聚乙二醇及其共聚物共混的含Cenderitide的薄膜表现出更高的释放动力学。通过使用超声喷涂机用包裹有CD-NP的PCL涂覆裸金属支架来制备Cenderitide洗脱支架(CES)。对CD-NP在体外细胞上的研究表明,CD-NP抑制人冠状动脉平滑肌细胞(HCaSMCs)的增殖,但对人脐静脉内皮细胞(HUVECs)的增殖没有影响。此外,长达7天释放的CD-NP对SMCs增殖具有抑制作用。在这项工作中生产的CES表明,释放的CD-NP在体外抑制HCaSMCs的增殖,但不阻碍HUVECs的增殖,这表明它有潜力在不延迟体内内皮化愈合的情况下减少ISR。