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Merck

In vitro evaluation of cenderitide-eluting stent I -an antirestenosis and proendothelization approach.

Journal of pharmaceutical sciences (2014-09-17)
Xu Wen Ng, Yingying Huang, Kerh Lin Liu, Soon Ghim Lim, Horng Haur Chen, John C Burnett, Yin Chiang Freddy Boey, Subbu S Venkatraman
ABSTRACT

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.

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Sigma-Aldrich
Methoxy poly(ethylene glycol)-block-poly(ε-caprolactone), 2k-2k
Sigma-Aldrich
Methoxy poly(ethylene glycol)-block-poly(ε-caprolactone), 5k-10k
Sigma-Aldrich
Methoxy poly(ethylene glycol)-block-poly(ε-caprolactone), 5k-2k
Sigma-Aldrich
Methoxy poly(ethylene glycol)-block-poly(ε-caprolactone), 2k-5k