摘要
背景:冠状动脉镁合金支架腐蚀速率及药物释放的双重调控是目前镁合金支架需要解决的重要课题。可降解载药聚合物涂层作为一种有前途的改性策略引发了广泛关注。目的:研究可降解载药聚合物涂层修饰对镁合金降解的影响,以及镁合金降解对可降解载药聚合物涂层药物释放的影响。方法:制备不同的药物聚合物溶液,溶液S1:西罗莫司0.01 g、聚三亚甲基碳酸酯0.005 g、二氯甲烷1 mL;溶液S2:西罗莫司0.01 g、聚三亚甲基碳酸酯0.01 g、二氯甲烷1 mL;S3:西罗莫司0.01 g、聚三亚甲基碳酸酯0.02 g、二氯甲烷1 mL;S2-1:西罗莫司0.01 g、聚三亚甲基碳酸酯0.01 g、0.001 g聚乙二醇400、二氯甲烷1 mL;S2-2:西罗莫司0.01 g、聚三亚甲基碳酸酯0.01 g、0.002 g聚乙二醇400、二氯甲烷1 mL。将5种药物聚合物溶液涂覆在AZ31镁合金表面制备涂层,对比涂层在镁合金基底上的药物释放行为差异,以及各涂层对镁合金腐蚀能力的影响;探索基底对西罗莫司-聚三亚甲基碳酸酯涂层的影响;考察各修饰镁合金的体外细胞相容性与血液相容性。结果与结论:①西罗莫司-聚三亚甲基碳酸酯涂层的修饰可以大幅增强镁合金的耐腐蚀能力,随着载药涂层的药物释放,涂层中形成微观水通道,涂层的腐蚀防护能力逐渐下降;浸泡后期金属降解产生的碱性微环境对药物释放起到一定的加速作用;涂层中药物占比的升高或聚乙二醇的加入会加快药物释放速率,但也加快了金属腐蚀速率;以上结果说明镁合金降解和药物涂层降解之间具有一定的双向促进效应,即镁合金的降解促进药物涂层的降解,而药物涂层的降解造成的孔隙也反过来进一步加快镁合金的降解。②5种药物涂层可有效抑制人血管内皮细胞与人血管平滑肌细胞的增殖与贴附,既不会引发溶血反应,也不影响内外源凝血机制(不同涂层参数的影响效果有小幅度的差异)。
BACKGROUND:The control of degradation and drug release of magnesium alloy stents is an urgent issue.Biodegradable drug-polymer coatings as promising modification strategies have aroused wide attraction.OBJECTIVE:To investigate the effect of drug-loaded biodegradable polymer coating on magnesium alloy degradation and the effect of magnesium alloy degradation on drug release of the drug-loaded biodegradable polymer coating.METHODS:Different drug-polymer solutions,solution S1,were prepared:sirolimus 0.01 g,poly(trimethylene carbonate)0.005 g,dichloromethane 1 mL;solution S2:sirolimus 0.01 g,poly(trimethylene carbonate)0.01 g,dichloromethane 1 mL;S3:sirolimus 0.01 g,poly(trimethylene carbonate)0.02 g,dichloromethane 1 mL;S2-1:sirolimus 0.01 g,poly(trimethylene carbonate)0.01 g,0.001 g polyethylene glycol 400,dichloromethane 1 mL;S2-2:sirolimus 0.01 g,poly(trimethylene carbonate)0.01 g,0.002 g polyethylene glycol 400,dichloromethane 1 mL.The coating was prepared by coating the surface of AZ31 magnesium alloy with five kinds of drug-polymer solutions.The difference in drug release behavior of the coating on the magnesium alloy substrate and the influence of each coating on the corrosion ability of magnesium alloy were compared.The influence of the substrate on sirolimus-poly(trimethylene carbonate)coating and in vitro cytocompatibility and hemocompatibility of the modified magnesium alloys were investigated.RESULTS AND CONCLUSION:(1)The modification of the sirolimus-poly(trimethylene carbonate)coatings could significantly enhance the corrosion resistance of the magnesium alloy.With the release of the drug,the anti-corrosion ability of the coatings gradually decreased due to the water channel formation of the coatings.The alkaline microenvironment caused by the magnesium alloy degradation slightly accelerated the release of sirolimus in the later immersion.The increased proportion of sirolimus in the coating or the increased proportion of polyethylene glycol in the coating increased the drug release rate,but decreased the anti-corrosion ability.The above results indicate that there is a two-way promotion effect between the degradation of magnesium alloy and the degradation of drug coating.That is,the degradation of magnesium alloy promotes the degradation of drug coating,and the pores caused by the degradation of drug coating in turn further accelerate the degradation of magnesium alloy.(2)The five kinds of drug coatings can effectively inhibit the proliferation and adhesion of human vascular endothelial cells and human vascular smooth muscle cells,neither causing the hemolytic reaction,nor affecting the endogenous and exogenous coagulation mechanism(the effect of different coating parameters has a small difference).
作者
赵铮
丁文飞
邵淑馨
王锦艳
蹇锡高
Zhao Zheng;Ding Wenfei;Shao Shuxin;Wang Jinyan;Jian Xigao(Department of Polymer Science,Dalian University of Technology,Dalian 116024,Liaoning Province,China;School of Medicine,Shanghai Jiao Tong University,Shanghai 200001,China)
出处
《中国组织工程研究》
CAS
北大核心
2023年第30期4836-4843,共8页
Chinese Journal of Tissue Engineering Research
基金
大连市科技基金重点项目(2018J11CY007),项目负责人:王锦艳。
关键词
镁合金支架
可降解
聚合物涂层
腐蚀速率调控
药物释放调控
聚三亚甲基碳酸酯
西罗莫司
体外生物相容性
magnesium alloy stent
biodegradable
polymer coating
corrosion rate regulation
drug release regulation
poly(trimethylene carbonate)
sirolimus
in vitro biocompatibility
