Boehler Christian, Asplund Maria
Freiburg Institute for Advanced Studies (FRIAS), Albert-Ludwigs-Universität, Freiburg, Germany; Department of Microsystems Engineering (IMTEK), Albert-Ludwigs-Universität Freiburg, Georges-Koehler-Allee 102, 79110, Freiburg, Germany.
J Biomed Mater Res A. 2015 Mar;103(3):1200-7. doi: 10.1002/jbm.a.35252. Epub 2014 Jul 28.
The possibility to release drugs from conducting polymers, like polypyrrole or poly(3,4-ethylenedioxythiophene) (PEDOT), has been described and investigated for a variety of different substances during the last years, showing a wide interest in these release systems. A point that has not been looked at so far however is the possibility of other substances, next to the intended ones, leaving the polymer film under the high voltage excursions during redox sweeping. In this study we target this weakness of commonly used detection methods by implementing a high precision analytical method (high-performance liquid chromatography) that allows a separation and subsequently a detailed quantification of all possible release products. We could identify a significantly more complex release behavior for a PEDOT:Dex system than has been assumed so far, revealing the active release of the monomer upon redox activation. The released EDOT could thereby be shown to result from the bulk material, causing a considerable loss of polymer (>10% during six release events) that could partly account for the observed degradation or delamination effects of drug-eluting coatings. The monomer leakage was found to be substantially higher for a PEDOT:Dex film compared to a PEDOT:PSS sample. This finding indicates an overestimation of drug release if side products are mistaken for the actual drug mass. Moreover the full picture of released substances implements the need for further studies to reduce the monomer leakage and identify possible adverse effects, especially in the perspective of releasing an anti-inflammatory substance for attenuation of the foreign body reaction toward implanted electrodes.
在过去几年中，已经对从导电聚合物（如聚吡咯或聚（3,4 - 乙烯二氧噻吩）（PEDOT））中释放药物的可能性进行了描述和研究，涉及多种不同物质，这表明人们对这些释放系统有着广泛的兴趣。然而，到目前为止尚未研究的一个问题是，除了预期释放的物质外，其他物质在氧化还原扫描过程中的高电压波动下离开聚合物薄膜的可能性。在本研究中，我们针对常用检测方法的这一弱点，采用了一种高精度分析方法（高效液相色谱法），该方法能够分离并随后详细定量所有可能的释放产物。我们发现PEDOT：右旋糖酐系统的释放行为比迄今为止所设想的要复杂得多，揭示了氧化还原激活后单体的活性释放。由此表明，释放出的3,4 - 乙烯二氧噻吩来自本体材料，导致聚合物大量损失（在六次释放过程中>10%），这可能部分解释了观察到的药物洗脱涂层的降解或分层效应。与PEDOT：聚苯乙烯磺酸盐样品相比，发现PEDOT：右旋糖酐薄膜的单体泄漏量要高得多。这一发现表明，如果将副产物误认为是实际药物质量，会高估药物释放量。此外，释放物质的全貌表明需要进一步研究以减少单体泄漏并确定可能的不良反应，特别是从释放抗炎物质以减轻对植入电极的异物反应的角度来看。
