Multiple Drug Delivery from Mesoporous Coating Realizing Combination Therapy for Bare Metal Stents

The simultaneous loading of multifunctional drugs has been regarded as one of the major challenges in the drug delivery system. Herein, a mesoporous silica coating was constructed on a bare metal stent surface by an evaporation-induced self-assembly method, in which both hydrophilic and hydrophobic drugs (heparin and rapamycin) were encapsulated by a one-pot method for the first time, and the release behaviors of these drugs were studied. The releasing mechanisms of these drugs were investigated in detail. Rapid release of heparin can achieve anticoagulation and endothelialization, whereas slow release of rapamycin can realize antiproliferative therapy for long term. In vitro hemocompatibility and promotion for proliferation of vein endothelial cells and the inhibition of smooth muscle cells were conducted. In vivo stent implantation results verify that the mesoporous silica coating with both heparin and rapamycin can successfully accelerate the endothelialization process and realize the antiproliferative therapy for as long as 3 months. These results indicate that this multifunctional mesoporous coating containing both hydrophilic and hydrophobic drugs might be a promising stent coating in the future.