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

Abstract

The use of drug-eluting coronary stents has led to significant reduction in in-stent restenosis (ISR), but led to delayed endothelialization, necessitating the prolonged use of expensive anti-thrombotic drugs with their side-effects. Cenderitide (CD-NP) is a novel anti-proliferative chimeric peptide of semi-endothelial origin. Our previous work in vitro has demonstrated; that the smooth muscle cells (SMCs) were inhibited significantly more than endothelial cells (ECs) which is the desirable feature of an anti-restenosis drug. This work reports the effects of implantation of a centeritide-eluting stent (CES) on in-stent restenosis and endothelialization in an in vivo model. cenderitide-eluting stents were produced by coating bare metallic stents with CD-NP entrapped in biodegradable poly(ε-caprolactone) using an ultrasonic spray coater. A total of 32 stents were successfully implanted into 16 pigs, and all animal survived for 28 days. The plasma levels of CD-NP were significantly higher in the CES group than in the control group (bare metal stents and polymer coated stent) at post-stenting, indicating the successful release of CD-NP into blood stream in vivo. Furthermore, SEM analysis results showed the greater endothelial coverage of the stent struts, as well as between the struts in CES group. Moreover, histological results showed mild inflammation, and low fibrin score at 28 days. However, plasma cGMP (second messenger, cyclic 3′,5′ guanosine monophosphate) does not show a significant difference, and the CES is also unable to show significant difference in terms on neointimal area and stenosis, in comparison to BMS at 28 days.

Lebetin 2, a Snake Venom-Derived Natriuretic Peptide, Attenuates Acute Myocardial Ischemic Injury through the Modulation of Mitochondrial Permeability Transition Pore at the Time of Reperfusion

“…Many of the reptilian peptides possess greater stability and less adverse side effects that give them advantages over their mammalian counterparts for therapeutic use. Recently, the chimeric peptide Cenderitide, designed from the snake venom dendroaspis natriuretic peptide (DNP) [ 71 ], has been found to exert potent cardioprotective action and is being evaluated in a phase II clinical trial for the treatment of cardiac ischemia [ 23 , 24 ]. Furthermore, unlike BNP, L2 presents the advantage to have a potent antiplatelet activity [ 72 ], which makes it a drug of choice for the treatment of acute myocardial infarction.…”

“…Previous preclinical and clinical studies have shown that these venom-derived peptides can act on multiple disease processes that play a role in negative outcomes associated with cardiac ischemia [ 22 ]. Certain clinical results have demonstrated that venom-derived natriuretic peptides may represent a superior treatment solution by offering therapeutic benefits in chronic heart failure [ 23 , 24 ].…”

Translation in cardiovascular stents and occluders: From biostable to fully degradable

“…Following this, a 4‐week pig study was carried out with a total of 32 stents implanted into 16 pigs . The in vivo results demonstrated significantly higher plasma levels of CD‐NP in the CES, and greater endothelial coverage of the stent struts compared with a control group (BMS and polymer‐coated stent) at poststenting, as shown in Figure .…”

Lebetin 2, a Snake Venom-Derived B-Type Natriuretic Peptide, Provides Immediate and Prolonged Protection against Myocardial Ischemia-Reperfusion Injury via Modulation of Post-Ischemic Inflammatory Response

“…Clinical results have shown that snake venom-derived compounds, such as Dendroaspis natriuretic peptide (DNP), may offer superior therapeutic benefits in chronic HF [14]. This is likely due to greater potency and increased stability as compared to human family members [15,16], while displaying similar benefits in cardiac ischemia through natriuretic receptor-mediated signaling [17,18].…”