Key Laboratory of Advanced Technology for Materials of Education Ministry, School of Materials Science and Engineering , Southwest Jiaotong University , Chengdu , Sichuan 610031 , China.
Max Bergmann Center of Biomaterials , Leibniz Institute of Polymer Research Dresden , Hohe Strasse 6 , 01069 Dresden , Germany.
ACS Appl Mater Interfaces. 2018 Mar 7;10(9):7649-7660. doi: 10.1021/acsami.7b06108. Epub 2017 Aug 28.
Sustained and controllable release characteristics are pivotal factors for novel drug delivery technologies. TiO nanotube arrays prepared by self-ordering electrochemical anodization are attractive for the development of biomedical devices for local drug delivery applications. In this work, several layers of polydopamine (PDA) were deposited to functionalize TiO nanotube arrays. The anticoagulant drug bivalirudin (BVLD) was used as a model drug. PDA extended the release period of BVLD and maintained a sustained release kinetic. Depending on the number of PDA layers, the release characteristics of BVLD improved, as there was a reduced burst release (from 45% to 11%) and extended overall release period from 40 days to more than 300 days in the case of 5 layers. Besides, the BVLD loaded 5-layer PDA coating maintained the high bioactivity of BVLD and effectively reduced the thrombosis formation by inhibition of the adhesion and denaturation of fibrinogen, platelets, and other blood components. Both in vitro and ex vivo blood evaluation results demonstrated that this coating significantly improved the hemocompatibility. These results confirmed the capability of PDA fitted TiO nanotube systems to be applied for local drug delivery over an extended period with well retained bioactivity and predictable release kinetics.
持续可控的释放特性是新型药物输送技术的关键因素。通过自组装电化学阳极氧化制备的 TiO 纳米管阵列对于局部药物输送应用的生物医学设备的发展具有吸引力。在这项工作中,沉积了几层聚多巴胺 (PDA) 以功能化 TiO 纳米管阵列。抗凝血药物比伐卢定 (BVLD) 被用作模型药物。PDA 延长了 BVLD 的释放周期并保持了持续释放动力学。根据 PDA 层的数量,BVLD 的释放特性得到了改善,因为在 5 层的情况下,突释(从 45%降至 11%)减少,总释放周期从 40 天延长至 300 天以上。此外,负载 5 层 PDA 涂层的 BVLD 保持了 BVLD 的高生物活性,并通过抑制纤维蛋白原、血小板和其他血液成分的粘附和变性有效减少了血栓形成。体外和体内血液评估结果表明,这种涂层显著改善了血液相容性。这些结果证实了 PDA 修饰的 TiO 纳米管系统具有延长的局部药物输送能力,同时保持了良好的生物活性和可预测的释放动力学。