In Vitro Evaluation of Cenderitide‐Eluting Stent I —An Antirestenosis and Proendothelization Approach

Abstract

Despite the success that drug eluting stents (DES) have achieved for minimizing in-stent restenosis (ISR), the anti-restenotic agents used in DES have been implicated in delayed endothelial healing and impairment of endothelial functions. Cenderitide (CD-NP) is a novel anti-proliferation chimeric peptide of semi-endothelial 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 (ECs). The micro-bicinchoninic acid (BCA) protein assay was used to investigate the CD-NP release from films and stents. Cenderitide-contained films blended with poly(ethylene glycol) and its copolymer exhibited higher release kinetics compared to neat PCL formulation. Cenderitide-eluting stents (CES) was produced by coating bare metallic stents with CD-NP entrapped poly(ε-caprolactone) using an ultrasonic spray coater. The investigation of CD-NP on in vitro cells revealed that CD-NP inhibits HCaSMCs proliferation but exhibits no effects on 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 endothelialisation healing in vivo.

In vivo Evaluation of Cenderitide-Eluting Stent (CES) II

“…We postulate that its semi-endothelial nature is not likely to inhibit ECs. Our in vitro cell studies 30 showed that CD-NP did not inhibit the growth of ECs, suggesting that CD-NP displayed cell-type discrimination inhibition. Our current in vivo study showed that CES has almost 100% endothelial coverage above struts, and between struts at 28 days.…”

“…Furthermore, the PEG-co-PCL copolymer excipient also helps by making the release less sensitive to emulsification condition 29 . Base on the in vitro cell studies 30 , the last group (10% 1k PEG-10k PCL) with 10% CD-NP loading was selected for further in vivo study, as it gave measurable subsequent release following an initial burst of ~27%.…”

“…Our previous work also showed that while the released cenderitide from cenderitide-eluting stent (CES) inhibits HCaSMCs proliferation it did not hamper HUVECs proliferation in vitro 30 . In this work, we report on the in vivo performance of cenderitide eluting stent in a pig model over 28 days.…”

New promising biodegradable polyesters derived from poly((R,S)-3,3-dimethylmalic acid) for cardiovascular applications

“…[21,103,104] are not perfect solutions. They have a limited diversity of their structures and adverse reactions can be caused by these polymers [105]. It is necessary that the biomaterial used to cover the stent should have good mechanical properties, appropriate surface properties, excellent hemocompatibility, good biocompatibility, and drug delivery capability.…”

Novel Biological Therapies Targeting Heart Failure

“…Cendiritide (CD- NP) is a recombinant engineered natriuretic peptide that combines elements of naturally occurring C- and D-type NP which optimizes its agonist action on both GC-A and B 65 , and may have unique anti-fibrotic activity. Combined with bio-engineered scaffolds and other drug delivery methods this novel peptide holds particular promise for vascular as well as myocardial disease 66,67 .…”