Abstract
In this study, we designed a novel drug-eluting coating for vascular implants consisting of a core coating of the anti-proliferative drug docetaxel (DTX) and a shell coating of the platelet glycoprotein IIb/IIIa receptor monoclonal antibody SZ-21. The core/shell structure was sprayed onto the surface of 316L stainless steel stents using a coaxial electrospray process with the aim of creating a coating that exhibited a differential release of the two drugs. The prepared stents displayed a uniform coating consisting of nano/micro particles. In vitro drug release experiments were performed, and we demonstrated that a biphasic mathematical model was capable of capturing the data, indicating that the release of the two drugs conformed to a diffusion-controlled release system. We demonstrated that our coating was capable of inhibiting the adhesion and activation of platelets, as well as the proliferation and migration of smooth muscle cells (SMCs), indicating its good biocompatibility and anti-proliferation qualities. In an in vivo porcine coronary artery model, the SZ-21/DTX drug-loaded hydrophobic core/hydrophilic shell particle coating stents were observed to promote re-endothelialization and inhibit neointimal hyperplasia. This core/shell particle-coated stent may serve as part of a new strategy for the differential release of different functional drugs to sequentially target thrombosis and in-stent restenosis during the vascular repair process and ensure rapid re-endothelialization in the field of cardiovascular disease.
Highlights
Cardiovascular diseases are among the most common diseases that give rise to disability and mortality
We reported the detection of sequential drug release of polymer-controlled core/shell nanoparticles prepared by coaxial electrospraying[31]
We described a novel drugeluting stents (DESs) coating consisting of particles with a core of the anti-proliferative drug DTX and a shell of SZ-21 deposited by coaxial electrospraying, which provides the biphasic diffusion-controlled release of each drug to effectively reduce in-stent restenosis and thrombosis
Summary
Cardiovascular diseases are among the most common diseases that give rise to disability and mortality. The use of coronary stents is commonplace in the treatment of such diseases[1]. Extensive data from experimental and clinical studies confirm that drugeluting stents (DESs) reduce the rate of restenosis compared with bare-metal stents (BMSs), there remains an increased risk of late stent thrombosis with DESs2–6. Percutaneous coronary intervention (PCI), especially involving stents, usually results in injury to the endothelium, inducing the activation and gathering of blood platelets to form thrombosis, and the stent may become a site for the adhesion of platelets before they are completely covered by neointima[4,7]. Other long-term clinical studies have reported that DESs loaded with antiproliferative agents suppressed the growth of neointima, delayed the re-endothelialization of stents, lengthened the time for activation of platelets, and increased the risk of late thrombosis[8]. The design of DESs in the future must consider these critical issues
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