Kempin Wiebke, Kaule Sebastian, Reske Thomas, Grabow Niels, Petersen Svea, Nagel Stefan, Schmitz Klaus-Peter, Weitschies Werner, Seidlitz Anne
Institute of Pharmacy, Center of Drug Absorption and Transport, University of Greifswald, 17487 Greifswald, Germany.
Institute for Biomedical Engineering, University of Rostock, 18119 Rostock, Germany.
Eur J Pharm Biopharm. 2015 Oct;96:322-8. doi: 10.1016/j.ejpb.2015.08.010. Epub 2015 Aug 28.
Lately, drug-coated balloons have been introduced in interventional cardiology as an approach to treat occluded blood vessel. They were developed for the rapid transfer of antiproliferative drugs during the angioplasty procedure in stenosed vessels with the intent to reduce the risk of restenosis. In this study five different paclitaxel (PTX) balloon coatings were tested in vitro in order to examine how solvents and additives influence coating stability and drug transfer rates. PTX-coated balloons were advanced through a guiding catheter and a simulated coronary artery pathway under perfusion and were then inflated in a hydrogel acceptor compartment. The fractions transferred to the gel, remaining on the balloon and the PTX lost in the simulated coronary pathway were then analysed. The results obtained suggest that the solvent used for the coating process strongly influences the surface structure and the stability of the coating. Ethanol/water and acetone based PTX coatings showed the lowest drug transfer rates to the simulated vessel wall (both <1%) due to their high drug losses during the prior passage through the coronary artery model (more than 95%). Balloons coated with PTX from ethyl acetate-solutions showed smaller drug loss (83%±9%), but most of the remaining PTX was not transferred (mean balloon residue approximately 15%). Beside the solvent, the use of additives seemed to have a great impact on transfer properties. The balloon pre-treatment with a crosslinked polyvinylpyrrolidone (PVP) film was able to increase the PTX transfer rate from less than 1% (without PVP) to approximately 6%. The best results in this study were obtained for balloon coatings with commercially available SeQuent© Please balloons containing the contrast agent iopromide. For this formulation drug transfer rates of approximately 17% were determined. Fluorescence microscopic imaging could visualize the particulate transfer of labelled PTX from the balloon surface during dilatation. The findings of this study underline the importance of drug adhesion and coating stability for the efficiency of PTX transfer.
最近，药物涂层球囊已被引入介入心脏病学领域，作为治疗血管闭塞的一种方法。它们是为在血管成形术过程中向狭窄血管快速输送抗增殖药物而开发的，目的是降低再狭窄风险。在本研究中，对五种不同的紫杉醇（PTX）球囊涂层进行了体外测试，以研究溶剂和添加剂如何影响涂层稳定性和药物转移率。将PTX涂层球囊通过引导导管并在灌注条件下经过模拟冠状动脉路径，然后在水凝胶接受腔中充气。随后分析转移到凝胶中的部分、残留在球囊上的部分以及在模拟冠状动脉路径中损失的PTX。所得结果表明，用于涂层过程的溶剂对涂层的表面结构和稳定性有很大影响。基于乙醇/水和丙酮的PTX涂层向模拟血管壁的药物转移率最低（均<1%），因为它们在先前通过冠状动脉模型的过程中药物损失很高（超过95%）。用乙酸乙酯溶液涂覆PTX的球囊药物损失较小（83%±9%），但剩余的大部分PTX未转移（球囊平均残留约15%）。除了溶剂外，添加剂的使用似乎对转移性能有很大影响。用交联聚乙烯吡咯烷酮（PVP）膜对球囊进行预处理能够将PTX转移率从小于1%（无PVP）提高到约6%。本研究中效果最佳的是含有造影剂碘普罗胺的市售SeQuent© Please球囊涂层。对于这种配方，测定的药物转移率约为17%。荧光显微镜成像可以观察到扩张过程中标记的PTX从球囊表面的颗粒状转移。本研究结果强调了药物附着力和涂层稳定性对PTX转移效率的重要性。
