Dextran sulfate as a drug delivery platform for drug-coated balloons: Preparation, characterization, in vitro drug elution, and smooth muscle cell response

Dextran sulfate as a drug delivery platform for drug-coated balloons: Preparation, characterization, in vitro drug elution, and smooth muscle cell response
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DOI:
10.1002/jbm.b.33494
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发表时间:
2016-10-01
影响因子:
3.4
通讯作者:
Mani, Gopinath
Mani, Gopinath
中科院分区:
工程技术3区
文献类型:
--
作者:
Lamichhane, Sujan;Anderson, Jordan;Mani, Gopinath

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药物涂层球囊(DCB)现已成为治疗外周动脉疾病的一种有前途的方法。然而,在球囊跟踪期间,来自球囊表面的大量药物损失,并且导致在患病部位处仅递送亚治疗剂量的药物。因此,在本研究中,研究了使用硫酸葡聚糖(DS)聚合物作为控制球囊药物释放的平台。将抗增殖药物紫杉醇(PAT)掺入DS膜(PAT-DS)中。SEM、FT-IR、DSC等表征表明,所制备的膜光滑均匀,PAT以无定形形式分散在DS基体中。平滑肌细胞(SMC)与对照DS和PAT-DS膜的相互作用的研究表明,两种膜均抑制SMC生长,PAT-DS膜的抑制作用上级。然后在球囊导管上制备PAT-DS涂层。当球囊回缩或充盈时,涂层的完整性保持良好。在这项研究中,使用DS平台将高达2.2 μ g/mm(2)的PAT加载到球囊上。药物洗脱研究表明,在球囊跟踪的典型时间段(1 min)内,仅10 - 20%的总PAT负载从PAT-DS涂层球囊释放,然后在球囊充盈和处理的典型时间段(1 min-4 min)内,约80%的总PAT负载释放。因此,本研究证明了使用DS作为控制球囊药物递送的平台。(c)2015年作者生物医学材料研究杂志B部分:应用生物材料出版的威利期刊,公司。J Biomed Mater Res Part B:Appl Biomater,104 B:1416-1430,2016。
Drug-coated balloons (DCBs) have now emerged as a promising approach to treat peripheral artery disease. However, a significant amount of drug from the balloon surface is lost during balloon tracking and results in delivering only a subtherapeutic dose of drug at the diseased site. Hence, in this study, the use of dextran sulfate (DS) polymer was investigated as a platform to control the drug release from balloons. An antiproliferative drug, paclitaxel (PAT), was incorporated into DS films (PAT-DS). The characterizations using SEM, FT-IR, and DSC showed that the films prepared were smooth and homogenous with PAT molecularly dispersed in the bulk of DS matrix in amorphous form. An investigation on the interaction of smooth muscle cells (SMCs) with control-DS and PAT-DS films showed that both films inhibited SMC growth, with a superior inhibitory effect observed for PAT-DS films. PAT-DS coatings were then produced on balloon catheters. The integrity of coatings was well-maintained when the balloons were either deflated or inflated. In this study, up to 2.2 mu g/mm(2) of PAT was loaded on the balloons using the DS platform. Drug elution studies showed that only 10 to 20% of the total PAT loaded was released from the PAT-DS coated balloons during the typical time period of balloon tracking (1 min) and then approximate to 80% of the total PAT loaded was released during the typical time period of balloon inflation and treatment (from 1 min to 4 min). Thus, this study demonstrated the use of DS as a platform to control drug delivery from balloons. (c) 2015 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1416-1430, 2016.