In vitro development of the nonthrombogenic stent

Abstract

Subacute thrombosis is a significant problem after stent insertion. Use of polymer-coated stents impregnated with drugs could reduce its incidence. We investigated the binding and elution kinetics and antithrombotic efficacy of three agents passively adsorbed onto commercially available polymer-coated stainless steel stents: (1) urokinase (UK), (2) an antirabbit platelt glycoprotein IIb/IIIa receptor antibody (AZ1), and (3) a UK-AZ1 chemical conjugate (C). Stent wire segments were immersed in¹²⁵Iodine-radiolabeled drug (0.1 or 1 g/L). Binding increased with immersion time and drug concentration (Fig. 1). Significantly more AZ1 or C than UK bound at both concentrations (p <0.01). Elution was assessed by perfusing stents with phosphate-saline buffer and 1% serum albumin. Anti-thrombotic efficacy was assessed by perfusing stents with¹¹¹Indium-labeled rabbit platelets. The results are shown in Tables 1 and 2. Significantly more AZ1 or C than UK remained bound to stents at all times (p <0.01). Stents with no bound drugs displayed significantly greater platelet adhesion (441 ± 28×10³) than stents with AZ1 or C (p <0.01). We conclude that platelet-targeted fibrinolytic agents can be passively bound to polymer-coated stents and are well retained even after prolonged continuous perfusion. Such agents retain their efficacy and reduce platelet deposition on stents more effectively than antiplatelet agents or nontargeted fibrinolytics alone. These agents may thus reduce stent-related thrombosis and require further in vivo evaluation.