Current vascular
drug-eluting stents based on immuno-proliferative drugs would reduce the rate of in-
stent restenosis (ISR) but may be associated with a higher risk of acute
stent thrombosis due to non-selective activity. In this paper, we aimed to develop a
polydopamine (PDA) coated chromium‑cobalt (CoCr)
stent functionalised with
EP224283 (Endotis Pharma SA), which combines both a GPIIbIIIa antagonist (
tirofiban moiety) and
a factor Xa inhibitor (
idraparinux moiety) to reduce acute
stent thrombosis. PDA-coated chromium‑cobalt (CoCr) samples were first immersed in a
polyethylenimine (PEI, pH 8.5)
solution to increase
amine function density (36.0 ± 0.1 nmol/cm2) on the CoCr surface. In a second step,
avidin was grafted onto CoCr-PDA-PEI through the
biotin linkage (strategy 1) or directly by coupling reactions (strategy 2). The
HABA titration proved the fixation of
biotin onto CoCr-PDA-PEI surface with a density of 0.74 nmol/cm2. The fixation of
avidin was demonstrated by water contact angle (WCA) and surface plasmon resonance (SPR). SEM micrograph shows the flexibility of the thin layer coated onto the
stent after balloon inflation. Independently of the strategy, a qualitative SEM analysis showed a reduction in platelet activation when the molecule
EP224283 was immobilised on
avidin. In parallel, the measurement of
anticoagulant activity (anti-Xa) revealed a higher anti-
factor Xa activity (2.24 IU/mL vs. 0.09 IU/mL in control) when
EP224283 was immobilised on
avidin. Interestingly, after seven days of degradation, the
anticoagulant activity was persistent in both strategies and looked more important with the strategy 2 than in strategy 1. Throughout this work, we developed an innovative vascular
stent through the immobilisation of
EP224283 onto CoCr-PDA-PEI-(
avidin) system, which provides a promising
solution to reduce ISR and
thrombosis after
stent implantation.