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 were inhibited significantly more than endothelial cells which is the desirable feature of an anti-restenosis drug. This work reports the effects of implantation of a centeritide-eluting stent (CES) on ISR and endothelialization in an in vivo model. CESs 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 from the stent 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.