Livnat Maya, Beyar Rafael, Seliktar Dror
The Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel.
J Biomed Mater Res A. 2005 Dec 1;75(3):710-22. doi: 10.1002/jbm.a.30474.
Drug-eluting stents signify a major achievement in reducing the incidence of coronary restenosis after percutaneous transluminal coronary angioplasty. However, where drug-eluting stents have been unsuccessful, endoluminal gel-paving strategies offer renewed optimism, mainly in a variety of vascular procedures requiring catheter-based sustained, localized delivery of therapeutic drugs, and biological factors. Despite promising results in animals, endoluminal paving has met with very limited clinical success because of the technical difficulties and stringent safety demands. The current study presents an alternative to gel paving using 40-mum-thick biodegradable polymeric films for deployment onto the artery wall during balloon angioplasty and stenting. The films are made from a durable yet compliant network of alginate and polyethylene glycol (PEG), and are securely held affixed to the vessel wall by the expanded stent struts. The alginate-based films are characterized by measuring their strength, elasticity, degree of swelling, degradability in water and saline, and drug release properties. The combination of alginate and PEG afforded the films sufficient strength and compliance for endoluminal deployment using an in vitro organ culture system. In characterizing the film degradability, it was discovered that the ionic concentration of the buffered saline was the main determinant in regulating the degradation kinetics and the release kinetics of the drug molecule Paclitaxel. These results suggest that the use of alginate-based, PEG-containing polymeric films for endoluminal coverage offers an alternative solution to conventional drug-eluting stents, with the added advantage of uniform endoluminal coverage of the treated segment and homogeneous endoluminal application of the active substance.
药物洗脱支架是经皮腔内冠状动脉成形术后降低冠状动脉再狭窄发生率的一项重大成就。然而，在药物洗脱支架效果不佳的情况下，腔内凝胶铺涂策略带来了新的希望，主要适用于各种需要通过导管进行治疗药物和生物因子持续、局部递送的血管手术。尽管在动物实验中取得了令人鼓舞的结果，但由于技术困难和严格的安全要求，腔内铺涂在临床上取得的成功非常有限。本研究提出了一种替代凝胶铺涂的方法，使用厚度为40微米的可生物降解聚合物薄膜，在球囊血管成形术和支架置入过程中部署在动脉壁上。这些薄膜由藻酸盐和聚乙二醇（PEG）组成的耐用且柔顺的网络制成，并通过扩张的支架支柱牢固地固定在血管壁上。通过测量藻酸盐基薄膜的强度、弹性、溶胀度、在水和盐水中的降解性以及药物释放特性来对其进行表征。藻酸盐和PEG的组合为薄膜提供了足够的强度和柔顺性，以便在体外器官培养系统中进行腔内部署。在表征薄膜降解性时发现，缓冲盐水的离子浓度是调节药物分子紫杉醇降解动力学和释放动力学的主要决定因素。这些结果表明，使用基于藻酸盐的含PEG聚合物薄膜进行腔内覆盖为传统药物洗脱支架提供了一种替代解决方案，其额外的优势在于对治疗段进行均匀的腔内覆盖以及对活性物质进行均匀的腔内应用。
