Immobilisation of an anti-platelet adhesion and anti-thrombotic drug (EP224283) on polydopamine coated vascular stent promoting anti-thrombogenic properties

• Published in: Materials Science & Engineering C 2020-08, Vol.113, p.110967-110967, Article 110967
• Main Authors: Bricout, Nicolas, Chai, Feng, Sobocinski, Jonathan, Hertault, Adrien, Laure, William, Ung, Alexandre, Woisel, Patrice, Lyskawa, Joel, Blanchemain, Nicolas
• Format: Article
• Language: English
• Subjects: Anticoagulants; Avidin; Avidin - chemistry; Balloon treatment; Biocompatible Materials - chemistry; Biocompatible Materials - pharmacology; Biotin; Biotin - analogs & derivatives; Biotin - chemistry; Biotin - pharmacology; Cell Survival - drug effects; Chemical and Process Engineering; Chemical reactions; Chemical Sciences; Chromium; Chromium - chemistry; Coating; Coatings; Cobalt; Cobalt - chemistry; Contact angle; Density; Drug delivery; Drug-Eluting Stents; Engineering Sciences; EP224283; Factor Xa - chemistry; Factor Xa - metabolism; Fixation; Human Umbilical Vein Endothelial Cells; Humans; Immobilization; Implantation; Implants; Indoles - chemistry; Material chemistry; Materials; Materials science; Oligosaccharides - chemistry; Oligosaccharides - metabolism; Oligosaccharides - pharmacology; Pharmaceuticals; Photomicrographs; Platelet Activation - drug effects; Platelet adhesion; Platelet Adhesiveness - drug effects; Platelets; Polydopamine; Polyethyleneimine; Polyethyleneimine - chemistry; Polymers; Polymers - chemistry; Qualitative analysis; Restenosis; Stent; Stents; Strategy; Surface functionalisation; Surface plasmon resonance; Surface Properties; Surgical implants; Thromboembolism; Thrombosis; Titration
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2020.110967

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. •Avidin was grafted onto CoCr-PDA-PEI through the biotin linkage or directly by coupling reactions.•The molecule EP224283 was successfully immobilised onto functionalized CoCr-PDA-stent.•The anticoagulant activity of the immobilised EP224283 molecule was preserved.•The second anti platelet adhesion activity of the molecule EP224283 was verified.•The biological activity was maintained for 7 days in in vitro conditions.