Analysis of anticoagulant and antiplatelet capacity of Nitinol-Polypyrrole devices doped with drugs

Abstract

Hemostasis plays an active role in atherosclerotic disease and arterial stenosis. Nitinol (NiTi) is used in several biomedical applications such as stents. Despite its biocompatibility, elasticity and corrosion resistance, some Ni2+ and Ti2+ ions may be released, resulting in local and systemic unwanted effects. The use of polypyrrole (PPy) coating, protects from ion release and, allows doping with drugs designed such as heparin (Hep) and sodium salicylate (NaSa). This work evaluates the effect on blood coagulation and platelet aggregation (PA) of NiTi-PPy devices (slices of 1cm2) doped with Hep (0.2; 0.3; 0.4 g/L), NaSa (0.1 and 0.5 M) or the combination of NaSa plus Hep (0.5M + 0.2 g/L). The slices were incubated 35 min with human plasma, and immediately after aliquots were taken for coagulation tests. Platelet poor plasma (PPP) was used for thrombin time (TT) and fibrinogen (F) measurements, and platelet rich plasma (PRP) for PA assays. TT was prolonged by Hep device. The anticoagulant effect was proportional to Hep concentration (25 - >120 sec; 0.2 to 0.4 g/L). F content was unchanged compared to PPP (316±16.5 vs 322±35.7 mg/dL). The 0.1 M NaSa slice inhibited PA (42% IPA). TT time was enlarged (34.8±9.9 sec.), F content decreased (15% vs PPP) and IAP was higher (90% IAP, p<0.05) using 0.5 M NaSa. Both drugs doping showed an anticoagulant additive effect (TT: 60±20.5 sec.) with significant F diminution (49% vs PPP). Scanning electron microscopy showed that slices that contained 0.5 M NaSa or NaSa plus Hep, exhibited a complex microtubular structure. The anticoagulant effect of NaSa slices could be due to the hiding of F in these three-dimensional structures. Platelet deposition was rule out since platelet counting in the remaining PRP was not changed respect to basal count. The results suggest that, these devices are able to produce an in situ beneficial regulation of hemostasis, and could represent a potential design to prevent restenosis of blood vessels.