Huang Li-Ying, Yang Ming-Chien
Department of Polymer Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan 106, ROC.
J Nanosci Nanotechnol. 2006 Sep-Oct;6(9-10):3163-70. doi: 10.1166/jnn.2006.430.
In order to develop drug-eluting cardiovascular stents, stainless steel (SUS316L) sheets were coated with hyaluronic acid (HA) and heparin (HEP), and their in vitro characteristics and drug release pattern were investigated. The surface of stainless steel (SS) was treated with nitric acid and followed by anchoring aminotrimethoxysilane (ATMS), then a nanolayer of HA was covalently immobilized onto the surface. Heparin was then covalently bonded to the HA-immobilized SS substrate. After repeating 1 to 5 cycles, 1 to 5 layers polyelectrolyte complex (PEC) nanobrush of HA/HEP were resulted with the thickness ranging from 280 to 630 nm (measured with ellipsometry). A model drug (sirolimus) was loaded in the HA/HEP layers at a density ranging from 1.02 to 3.12 microg/cm2. The SS-ATMS-HA-HEP substrates were evidenced by X-ray photoelectron spectroscope (XPS), contact angle, and AFM measurement. The effect of this surface modification on the coagulation time of the resulting SS substrates was investigated. The results show that the multilayer HA/HEP stainless steel would exhibit higher anticoagulant activity than pure SS substrates. In addition, the results of the in vitro drug delivery study showed that release of sirolimus from the 5-layer-HA-HEP stainless steel was able to maintain more than 30 days. Thus layer-by-layer HA/HEP PEC can improve the hemocompatibility of SS surface and control the drug released rate by multiple layers of HA/HEP PEC. These results indicate that the multi-layer HA/HEP PEC coated stainless steel would be suitable for drug eluting stents.
为了研发药物洗脱心血管支架，在不锈钢（SUS316L）片材上涂覆透明质酸（HA）和肝素（HEP），并研究其体外特性和药物释放模式。不锈钢（SS）表面先用硝酸处理，然后锚定氨基三甲氧基硅烷（ATMS），接着将HA纳米层共价固定在表面。随后将肝素共价键合到固定有HA的SS基底上。重复1至5个循环后，形成了1至5层的HA/HEP聚电解质复合物（PEC）纳米刷，厚度范围为280至630纳米（用椭偏仪测量）。将模型药物（西罗莫司）以1.02至3.12微克/平方厘米的密度加载到HA/HEP层中。通过X射线光电子能谱仪（XPS）、接触角和原子力显微镜测量对SS-ATMS-HA-HEP基底进行了表征。研究了这种表面改性对所得SS基底凝血时间的影响。结果表明，多层HA/HEP不锈钢比纯SS基底表现出更高的抗凝血活性。此外，体外药物递送研究结果表明，西罗莫司从5层HA-HEP不锈钢中的释放能够维持30多天。因此，逐层的HA/HEP PEC可以改善SS表面的血液相容性，并通过多层HA/HEP PEC控制药物释放速率。这些结果表明，多层HA/HEP PEC涂层不锈钢适用于药物洗脱支架。
