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一种无聚合物的紫杉醇洗脱冠状动脉支架:溶剂、药物浓度及涂层方法的影响

A polymer-free Paclitaxel eluting coronary stent: effects of solvents, drug concentrations and coating methods.

作者信息

Lamichhane Sujan, Gallo Annemarie, Mani Gopinath

机构信息

Biomedical Engineering Program, The University of South Dakota, 4800 N. Career Ave, Suite 221, Sioux Falls, SD, 57107, USA.

出版信息

Ann Biomed Eng. 2014 Jun;42(6):1170-84. doi: 10.1007/s10439-014-1003-y. Epub 2014 Apr 5.

Abstract

Some polymer coatings used in drug-eluting stents (DES) cause adverse reactions. Hence, the use of self-assembled monolayers (SAMs) as a polymer-free platform to deliver an anti-proliferative drug (paclitaxel-PAT) from 2D metal substrates was previously demonstrated. In this study, we optimized the PAT coating on SAMs coated 3D coronary stents. For the optimization process, we investigated the effects of solvents (ethanol, DMSO, and their mixtures), drug concentrations (2, 3, 4, 8, and 12 mg/mL) in the coating solution, and coating methods (dip and spray) on PAT deposition. A solvent mixture of 75:25 v/v Et-OH:DMSO was determined to be the best for obtaining smooth and homogenous PAT coating. PAT coated stents prepared using 8 mg/mL and 3 mg/mL concentrations of PAT by dip and spray coating methods, respectively, were optimal in terms of carrying adequate drug doses (0.35 µg/mm(2) for dipping and 0.76 µg/mm(2) for spraying) as well as negligible defects observed in the coating. PAT was successfully released from SAMs coated stents in a biphasic manner with an initial burst followed by a sustained release for up to 10 weeks. Thus, this study sheds light on the effects of solvents, drug concentrations, and coating methods on preparing a polymer-free DES.

摘要

一些用于药物洗脱支架(DES)的聚合物涂层会引起不良反应。因此,先前已证明使用自组装单分子层(SAMs)作为无聚合物平台从二维金属基底递送抗增殖药物(紫杉醇-PAT)。在本研究中,我们优化了涂覆在三维冠状动脉支架上的SAMs上的PAT涂层。在优化过程中,我们研究了溶剂(乙醇、二甲基亚砜及其混合物)、涂层溶液中的药物浓度(2、3、4、8和12mg/mL)以及涂覆方法(浸渍和喷涂)对PAT沉积的影响。已确定体积比为75:25的乙醇-二甲基亚砜混合溶剂最适合获得光滑且均匀的PAT涂层。分别通过浸渍和喷涂涂覆方法使用8mg/mL和3mg/mL浓度的PAT制备的PAT涂覆支架,在携带足够药物剂量(浸渍为0.35µg/mm²,喷涂为0.76µg/mm²)以及涂层中观察到的缺陷可忽略不计方面是最佳的。PAT以双相方式从涂覆有SAMs的支架中成功释放,最初有一个突发释放,随后持续释放长达10周。因此,本研究揭示了溶剂、药物浓度和涂覆方法对制备无聚合物DES的影响。

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