Dual Drug-Eluting Stents Coated with Multilayers of Hydrophobic Heparin and Sirolimus

Abstract

Polymer coatings for stents are considered one of the key factors that lead to adverse cardiac events after coronary arterial stenting. This study presents a dual drug-eluting stent (DES) that is coated with multilayers of Duraflo heparin and sirolimus but containing no other organic polymers. The hydrophobic Duraflo heparin coating was used to improve the hemocompatibility of the stent and serve as a drug reservoir for the controlled release of sirolimus, thus avoiding inflammatory reactions induced by the conventional polymers. The Duraflo heparin and sirolimus were coated layer-by-layer onto the stent surface using a homemade spray-coating device. The drug loading amount can be easily controlled by adjusting the numbers of layers applied and the concentration of the drug solution, indicating the developed coating process is reproducible and well-controlled. After balloon expansion, the coating did not crack or peel off, which demonstrates that the sirolimus/Duraflo heparin coating layers tightly adhere to the stent surface. The activated partial thromboplastin time (APTT) assay showed that the Duraflo heparin coating significantly prolonged the APTT from 27.3 ± 0.3 s to 69.7 ± 6.2 s, demonstrating the anticoagulant ability of the coated stents. The dual DES exhibited a nearly linear sustained-release profile of Duraflo heparin and an initial burst release followed by a slow release of sirolimus. Less than 15% of heparin was released from the DES within 14 days, indicating the stent can maintain its antithrombotic surface for a long time. Because of the layer-by-layer structure, the most outer layer of Duraflo heparin coating may act as a diffusion barrier to retard sirolimus release from the stent. These results confirm that the dual DESs enable simultaneous delivery of antithrombotic and antiproliferative drugs and have potential for the treatment of coronary artery disease.