柯佑,黄楠,熊开琴,马青,周楠,吴钰,涂秋芬.具有病灶治愈功能的淫羊藿苷洗脱涂层修饰血管支架[J].表面技术,2024,53(18):219-230.
KE You,HUANG Nan,XIONG Kaiqin,MA Qing,ZHOU Nan,WU Yu,TU Qiufen.Icariin-eluting Coating Modified Vascular Stent with Lesion Healing Function[J].Surface Technology,2024,53(18):219-230 |
| 具有病灶治愈功能的淫羊藿苷洗脱涂层修饰血管支架 |
| Icariin-eluting Coating Modified Vascular Stent with Lesion Healing Function |
| 投稿时间：2023-10-17 修订日期：2023-12-26 |
| DOI：10.16490/j.cnki.issn.1001-3660.2024.18.020 |
| 中文关键词: 淫羊藿苷 药物洗脱涂层 促内皮 抗炎 抗血栓 |
| 英文关键词:icariin drug-eluting coating pro-endothelial anti-inflammatory antithrombosis |
| 基金项目: |
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| Author | Institution |
| KE You | Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu 610031, China;Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China |
| HUANG Nan | Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China |
| XIONG Kaiqin | Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu 610031, China |
| MA Qing | Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China |
| ZHOU Nan | Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu 610031, China;Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China |
| WU Yu | Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China |
| TU Qiufen | Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu 610031, China;Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China |
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| 中文摘要: |
| 目的 开发一种ICA洗脱涂层，以聚乳酸-羟基乙酸共聚物(PLGA)为药物递送载体，实现靶向治疗。方法 利用超声雾化喷涂技术在血管支架表面构建ICA洗脱涂层，利用傅里叶变换红外吸收光谱仪(FTIR)、水接触角(WCA)检测仪和场发射扫描电子显微镜(SEM)等表征手段对涂层的材料学性质进行检测;通过紫外分光光度计(UV-Vis)检测药物释放行为;通过体外溶血率和血小板的黏附与激活实验验证该涂层的血液相容性;通过体外细胞实验进一步评价该涂层的细胞相容性。结果 研究结果显示，涂层构建成功，且ICA的装载并未对PLGA涂层的力学性能产生影响，同时实现了ICA体外至少28 d的持续释放。血液相容性的评价结果显示，该涂层有效减少了血小板的黏附和聚集，且该涂层能够抑制SMCs的异常增殖，促进ECs的黏附、增殖，有效调控巨噬细胞向组织修复型转变。结论 ICA洗脱支架涂层显示出潜在的抗血栓、抗炎、促内皮和抑制平滑肌细胞异常增殖的特性，有望为心血管疾病患者提供一种安全和有效的治疗选择。 |
| 英文摘要: |
| Cardiovascular disease, as the leading cause of global human disease-related deaths, is one of the most prevalent and deadly health threats worldwide. Percutaneous coronary intervention with the implantation of cardiovascular stents is considered one of the most effective treatment methods. Stents act as mechanical support, providing structural support to maintain the normal patency of blood vessels. However, currently used stents still face issues such as intrastent thrombosis and restenosis. Drug-eluting stents (DES) loaded with drugs like paclitaxel and rapamycin have reduced the risk of restenosis to some extent but may induce de novo atherosclerosis and late stent thrombosis. These anti-tumor drugs can inhibit the proliferation of smooth muscle cells but inevitably hinder the repair and healing of vascular endothelial cells. Therefore, the ideal vascular stent should not only inhibit abnormal smooth muscle cell proliferation but also possess anti-inflammatory, anti-thrombotic, and endothelial-promoting functions. Icariin (ICA) is a flavonoid compound extracted from the Epimedium plant, known for its various biological functions, including antioxidant, anti-inflammatory, antimicrobial, and anti-tumor properties. In this study, an icariin drug-eluting coating with lesion healing capabilities was constructed on the surface of vascular stents with the ultrasonic atomization spray technology. With PLGA as a drug delivery system carrier, it not only exhibited good biocompatibility but also preserved the activity of ICA, enabling targeted drug delivery and increasing treatment precision. This coating enhanced the biocompatibility of the material surface without altering the base material. The study involved the preparation of drug-eluting coatings on 316L SS stainless steel specimens (1 cm × 1 cm) and medical-grade 316L SS vascular stents. In a 2 mg/mL PLGA solution (solvent:tetrahydrofuran), different proportions of icariin (0%, 10%, 20%, 30%, 40% by mass) were added. Drug-loaded PLGA coatings were then fabricated onto the substrates by evaporative deposition or ultrasound atomization spraying techniques. The ultrasound atomization system operated at 2 W of ultrasound power, with a solution flow rate of 0.75 cm/sec, and a total of 40 deposition cycles. The chemical composition of the coatings was analyzed by Fourier-transform infrared spectroscopy (FTIR), while the wettability of the samples was determined through a water contact angle (WCA) measurement. The microstructure of the coatings on the vascular stents was observed by scanning electron microscopy (SEM). The drug release behavior of the coatings was assessed by UV-Vis spectrophotometry. In vitro experiments were conducted to evaluate the blood compatibility of the coatings, including hemolysis rate and platelet adhesion and activation. Additionally, in vitro cell experiments were performed to assess the influence of the drug-eluting coatings on endothelial cells, smooth muscle cells, and macrophage proliferation. Immunofluorescence staining was employed to evaluate the effects of icariin-eluting coatings on the adhesion and phenotype of endothelial cells, smooth muscle cells, and macrophages. The results from FTIR, WCA, and SEM confirmed the successful preparation of icariin-eluting coatings. These coatings exhibited sustained drug release in vitro for at least 28 days. Blood compatibility assessments demonstrated that the coatings met the hemolysis rate requirements for biomedical implants and exhibited a significant inhibitory effect on platelet adhesion and aggregation. In vitro cell compatibility results indicated that icariin-eluting coatings promoted the adhesion and proliferation of endothelial cells, suppressed smooth muscle cell proliferation, and effectively regulated macrophage inflammation. Based on the in vitro biocompatibility results, the optimal preparation parameter was determined to be an icariin content of 30%. In summary, the icariin-eluting stent developed in this study achieve long-term and stable icariin release, accompanied by properties such as anti-thrombotic, anti-inflammatory, endothelial promotion, and inhibition of smooth muscle cell abnormal proliferation. This stent hold the potential to offer a safe and effective therapeutic option for patients with cardiovascular diseases. |
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