Drug-loading Polylactic Acid Stent And Its Biocompatibility Evaluation

The first angioplasty was performed by doctor Gruentzig in 1977, which is the start of the new epoch of percutaneous transluminal coronary angioplasty(PTCA). After that, this field evolved rapidly and has gone through PTCA, bare metal stent(BMS) and drug-eluting stent(DES) eras. Clinical application indicated that DES is successful in dealing with the acute vascular occlusion after PTCA and the postoperative restenosis of BMS. But DES has its own issues: these permanently existed metal implants in vessels will limit the normal movement of blood vessels and cause inflammatory reaction of vascular wall, which in turn will lead to a sequence of immunological and biochemical reactions as well as arterial wall hyperplasia and in-stent restenosis. Moreover, the anti-proliferative drug coating on the surface of DES suppresses the vascular smooth muscle hyperplasia while delay the renovate of vascular endothelium and result in late in stent thrombosis. In order to overcome these obstacles that conventional DES have faced, totally bioresorbable stents were developed. These types of stents can be completely resorbed in vivo, complete the impossible functions that metal stents can not achieve, such as normal physiological function recovering of the vessel, relieving inflammation of the blood vessel walls, release to the side-branch blood vessel, interventional therapy in the same position, and being compatible with magnetic resonance imaging, etc.A good endothelialization is the premise for the safety degradation in the body of the biodegradable stent, the study found that antiproliferative drug-loading nanoparticles can effectively inhibit the proliferation of vascular smooth muscle cells, and had a little effect on vascular endothelial cell proliferation, this will help to support to complete the good endothelialization finally. In addition, drug-loading nanoparticles can also achieve efficient loading efficiency and drug slow-release effect due to its large specific surface area. So in this paper, we prepared the sirolimus-PDLLA nanoparticles by the method of traditional emulsion solution volatilization, rapamycin and polymer drug carrier(PDLLA) were dissolved in acetone solvent, then mixed the solution with aqueous containing surfactants under the ultrasonic, the sirolimus loading nanoparticles were prepared after organic solvent volatilized which had a diameter range from 200 nm to 500 nm. Tests showed that the drug-loading nanoparticles coating efficiency was at about 90%, and the drug release rate could reach 70% when the NPs were releasing in a eluting buffer for 15 days.Polylactic acid has good biological compatibility and biodegradable properties, but to some extent, its strong hydrophobicity limits its development in the field of biodegradable stents. In this work, Ar low temperature plasma technology was applied to graft hydrophilic polymer polyvinylpyrrolidone(PVP) and polyvinyl acetate(PVAc) on the surface of PDLLA stent. Contact angle test showed that surface contact angle of the plasma grafted stent can fall from 105-110° to 22°, implying a change from strong hydrophobicity to hydrophilicity. In vitro cell adhesion experiments showed that, after plasma treatment, the surface of the material is hydrophilic and the cell adhesion was significantly improved, facilitating the cell growth.The PLLA scaffold treated by low temperature plasma grafting achieved a high hydrophily and obtained the certain adhesion performance which could effectively adsorb the sirolimus-loading nanoparticles. Therefore, the drug-loading nanoparticles coating stent was obstained by dipping the plasma treated PLLA scaffold into the suspension of drug-loading nanoparticles. Cell co-culture experiments show that the nanoparticles coating stent has a good biocompatibility and can effectively inhibit the proliferation of vascular smooth muscle cells, while has a little effects on vascular endothelial cell proliferation, thus it can help complete a better endothelialization and finally reduce the occurrence of in-stent restenosis.