Thiruppathi Eagappanath, Mani Gopinath
Biomedical Engineering Program, The University of South Dakota , 4800 North Career Avenue, Sioux Falls, South Dakota 57107, United States.
Langmuir. 2014 Jun 3;30(21):6237-49. doi: 10.1021/la501448h. Epub 2014 May 21.
Antiproliferative drugs such as paclitaxel and sirolimus are delivered from stents to inhibit the growth of smooth muscle cells (SMCs) for preventing neointimal hyperplasia. However, these drugs delay the growth of endothelial cells (ECs) as well and cause late stent thrombosis. We recently demonstrated the use of Vitamin-C (l-ascorbic acid, l-AA) over paclitaxel and sirolimus for inhibiting SMCs growth and promoting EC growth simultaneously. In this study, we have investigated the delivery of l-AA from CoCr alloy surfaces for potential use in stents. A polymer-free phosphoric acid (PA) platform and a polymer-based poly(lactic-co-glycolic acid) (PLGA) platform were used for coating l-AA onto CoCr surfaces. For the PA platform, FTIR confirmed that the PA was coated on CoCr, while the AFM showed that the PA coating on the CoCr surface was homogeneous. The successful deposition of l-AA on PA-coated CoCr was also confirmed by FTIR. The uniform distribution of l-AA crystals on PA-coated CoCr was shown by SEM, optical profilometer, and AFM. The drug release studies showed that l-AA (276 μg/cm(2)) was burst released from the PA platform by 1 h. For the PLGA platform, SEM showed that the l-AA incorporated polymer films were smoothly and uniformly coated on CoCr. FTIR showed that l-AA was incorporated into the bulk of the PLGA film. DSC showed that the l-AA was present in an amorphous form and formed an intermolecular bonding interaction with PLGA. The drug release studies showed that l-AA was sustained released from the PLGA coated CoCr for up to 24 h. The SEM, FTIR, and DSC characterizations of samples collected post drug release shed light on the mechanism of l-AA release from PLGA coated CoCr. Thus, this study demonstrated the delivery of l-AA from biomaterial surfaces for potential applications in stents and other implantable medical devices.
抗增殖药物如紫杉醇和西罗莫司从支架释放，以抑制平滑肌细胞（SMC）生长，预防新生内膜增生。然而，这些药物也会延缓内皮细胞（EC）生长，并导致晚期支架血栓形成。我们最近证明，与紫杉醇和西罗莫司相比，维生素C（L-抗坏血酸，L-AA）可同时抑制SMC生长并促进EC生长。在本研究中，我们研究了L-AA从钴铬合金表面的释放情况，以探讨其在支架中的潜在应用。使用无聚合物的磷酸（PA）平台和基于聚合物的聚乳酸-乙醇酸共聚物（PLGA）平台将L-AA涂覆在钴铬表面。对于PA平台，傅里叶变换红外光谱（FTIR）证实PA已涂覆在钴铬上，而原子力显微镜（AFM）显示钴铬表面的PA涂层均匀。FTIR也证实了L-AA成功沉积在PA涂覆的钴铬上。扫描电子显微镜（SEM）、光学轮廓仪和AFM显示L-AA晶体在PA涂覆的钴铬上均匀分布。药物释放研究表明，L-AA（276μg/cm²）在1小时内从PA平台突发释放。对于PLGA平台，SEM显示掺入L-AA的聚合物膜在钴铬上平滑且均匀地涂覆。FTIR表明L-AA掺入到PLGA膜的主体中。差示扫描量热法（DSC）表明L-AA以无定形形式存在，并与PLGA形成分子间键合相互作用。药物释放研究表明，L-AA从PLGA涂覆的钴铬上持续释放长达24小时。药物释放后收集的样品的SEM、FTIR和DSC表征揭示了L-AA从PLGA涂覆的钴铬上释放的机制。因此，本研究证明了L-AA从生物材料表面的释放，其在支架和其他可植入医疗设备中具有潜在应用。
