title: In vitro evaluation of cenderitide-eluting stent I -an antirestenosis and proendothelization approach.
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.
authors.affiliation: School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore.
authors.forename: Xu Wen
authors.initials: XW
authors.lastname: Ng
authors.affiliation: School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore.
authors.forename: Kerh Lin
authors.initials: KL
authors.lastname: Liu
authors.affiliation: School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore.
authors.forename: Soon Ghim
authors.initials: SG
authors.lastname: Lim
authors.affiliation: Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905.
authors.forename: Horng Haur
authors.initials: HH
authors.lastname: Chen
authors.affiliation: Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905.
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
authors.affiliation: School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore.
authors.forename: Yin Chiang
authors.initials: YC
authors.lastname: Freddy Boey
authors.affiliation: School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore. Electronic address: assubbu@ntu.edu.sg.
authors.forename: Subbu S
authors.initials: SS
authors.lastname: Venkatraman
mesh_terms: D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D023903:Coronary Restenosis / Q000473:pathology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004355:Drug Stability; D054855:Drug-Eluting Stents; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007700:Kinetics; D008422:Materials Testing; D008670:Metals / Q000737:chemistry; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000473:pathology; D045265:Natriuretic Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011474:Prosthesis Design; D012910:Snake Venoms / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility
chemical_list: D002317:Cardiovascular Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008670:Metals; D045265:Natriuretic Peptides; D011091:Polyesters; D012910:Snake Venoms; C016240:polycaprolactone; D011092:Polyethylene Glycols; C575835:cenderitide
keywords: CD-NP; biodegradable polymer; biomaterials; controlled release; excipients; formulation; natriuretic peptide; peptide delivery