Preparation, characterization, in vitro drug release, and cellular interactions of tailored paclitaxel releasing polyethylene oxide films for drug-coated balloons
Preparation, characterization, in vitro drug release, and cellular interactions of tailored paclitaxel releasing polyethylene oxide films for drug-coated balloons
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DOI：
10.1016/j.actbio.2015.09.036
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发表时间：
2016-01-01
影响因子：
9.7
通讯作者：
Mani, Gopinath
中科院分区：
文献类型：
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作者：
Anderson, Jordan A.;Lamichhane, Sujan;Mani, Gopinath
药物涂层球囊(DCB)用于治疗各种心血管疾病。目前可用的DCB单独或使用不同的载体在球囊表面携带药物。几项研究表明，在气囊追踪过程中，血流中会丢失大量药物，以便在治疗地点仅提供亚治疗水平的药物。本研究致力于开发紫杉醇(PAT)聚氧化乙烯(PEO)薄膜(PAT-PEO)作为DCB的受控给药载体。在这项研究中开发了一系列PAT-PEO薄膜，仅在特定的时间间隔提供90%的药物的量身定制释放，这是进行球囊治疗所需的时间框架。用扫描电子显微镜、傅里叶变换红外光谱和差示扫描量热仪对PAT-PEO薄膜进行了表征，结果表明所制备的PAT-PEO薄膜均一，PAT分子分散在PEO基质中。力学测试表明，所制备的PAT-PEO薄膜具有柔韧性，加入PAT后，其屈服强度和拉伸强度不受影响。研究了与对照PEO和PAT-PEO膜相互作用的平滑肌细胞(SMC)的存活率、增殖、形态和表型。所有对照-PEO和PAT-PEO薄膜对SMC的生长都有明显的抑制作用，抑制程度强烈地依赖于所用聚合物的w/v%。在气球上生产了PAT-PEO涂层。PAT-PEO涂层的完整性得到了很好的维护，在气囊充气或放气过程中没有出现任何机械缺陷。药物释放研究表明，在最初的1分钟(典型的球囊追踪时间)内，只有15%的加载PAT从球囊中释放，而80%的PAT在1分钟到4分钟(典型的球囊治疗时间)之间释放。因此，这项研究证明了PEO作为气球的替代药物输送系统的使用。意义陈述动脉粥样硬化是每年数百万患者心血管疾病(CVD)的主要原因。药物涂层球囊(DCB)通常用于治疗各种心血管疾病。然而，在目前使用的几种DCB中，在气囊追踪过程中，相当数量的药物在血流中丢失，以便在治疗部位仅提供亚治疗水平的药物。在这项研究中，含有紫杉醇的聚氧化乙烯(PEO)薄膜具有独特的优势，包括专为球囊治疗量身定做的药物释放轮廓，具有分子分散药物的均质薄膜，柔性和延展性薄膜，并显示出显著的抑制平滑肌细胞生长的作用。因此，本研究证明了PEO作为DCBs的替代给药平台来提高其疗效。(C)2015年Acta Materialia Inc.由爱思唯尔有限公司出版。这是CC BY-NC-ND许可证(http://creativecommons.org/licenses/by-nc-nd/4.0/).下的一篇开放获取文章
Drug-coated balloons (DCBs) are used to treat various cardiovascular diseases. Currently available DCBs carry drug on the balloon surface either solely or using different carriers. Several studies have shown that a significant amount of drug is lost in the blood stream during balloon tracking to deliver only a sub-therapeutic level of drug at the treatment site. This research is focused on developing paclitaxel (PAT) loaded polyethylene oxide (PEO) films (PAT-PEO) as a controlled drug delivery carrier for DCBs. An array of PAT-PEO films were developed in this study to provide tailored release of >90% of drug only at specific time intervals, which is the time frame required for carrying out balloon-based therapy. The characterizations of PAT-PEO films using SEM, FTIR, and DSC showed that the films developed were homogenous and the PAT was molecularly dispersed in the PEO matrix. Mechanical tests showed that most PAT-PEO films developed were flexible and ductile, with yield and tensile strengths not affected after PAT incorporation. The viability, proliferation, morphology, and phenotype of smooth muscle cells (SMCs) interacted with control-PEO and PAT-PEO films were investigated. All control-PEO and PAT-PEO films showed a significant inhibitory effect on the growth of SMCs, with the degree of inhibition strongly dependent on the w/v% of the polymer used. The PAT-PEO coating was produced on the balloons. The integrity of PAT-PEO coating was well maintained without any mechanical defects occurring during balloon inflation or deflation. The drug release studies showed that only 15% of the total PAT loaded was released from the balloons within the initial 1 min (typical balloon tracking time), whereas 80% of the PAT was released between 1 min and 4 min (typical balloon treatment time). Thus, this study demonstrated the use of PEO as an alternate drug delivery system for the balloons.Statement of SignificanceAtherosclerosis is primarily responsible for cardiovascular diseases (CVDs) in millions of patients every year. Drug-coated balloons (DCBs) are commonly used to treat various CVDs. However, in several currently used DCBs, a significant amount of drug is lost in the blood stream during balloon tracking to deliver only a sub-therapeutic level of drug at the treatment site. In this study, paclitaxel containing polyethylene oxide (PEO) films were developed to provide unique advantages including drug release profiles specifically tailored for balloon-based therapy, homogeneous films with molecularly dispersed drug, flexible and ductile films, and exhibits significant inhibitory effect on smooth muscle cell growth. Thus, this study demonstrated the use of PEO as an alternate drug delivery platform for DCBs to improve its efficacy. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).