Design and testing of hydrophobic core/hydrophilic shell nano/micro particles for drug-eluting stent coating

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. A cardiovascular stent that releases drugs to prevent artery blockage has been developed by researchers in China, the United Kingdom and Italy. A common treatment for cardiovascular disease, coronary stents ensure blood flow by keeping arteries open. Many of these stents also release drugs to repair the damage that these devices can do to surrounding tissue. Such damage includes the proliferation of smooth muscle cells that build up as scar tissue on the inside of the artery. Guixue Wang and Tieying Yin from the Bioengineering College of Chongqing University, China, and co-workers sprayed stainless-steel stents with particles consisting of a shell of the anti-proliferative drug docetaxel and an antibody core which prevents the formation of blood clots. Tests of their device using a pig coronary artery showed that smooth muscle cell proliferation was inhibited. Hydrophobic core/hydrophilic shell platelet glycoprotein IIb/IIIa receptor monoclonal antibody (SZ-21)/docetaxel (DTX) dual-drug loaded stents exhibiting a uniform coating of nano/micro particles using coaxial electrospray were prepared. Experimental data combined with a biphasic mathematical model indicated the release of the two drugs conformed to a diffusion-controlled release system. The core/shell SZ-21/DTX dual-drug loaded stents showed good blood and cell compatibility, promoted re-endothelialization in vivo and reduced in-stent restenosis in porcine coronary arteries. The coaxial electrospray technique is a one-step and effective technique for stent coating with multiple drugs and has great potential for helping to create the enhanced implants of the future.