Grindulis Karlis, Matusevica Nikola Gabriela, Kozlova Vendija, Rimsa Roberts, Klavins Kristaps, Mozolevskis Gatis
Cellbox Labs, Riga, 1063, Latvia.
Institute of Solid State Physics, University of Latvia, Riga, 1063, Latvia.
Sci Rep. 2025 Apr 23;15(1):14012. doi: 10.1038/s41598-025-97111-2.
Accurate risk assessment in drug development is crucial, as conventional in vitro and in vivo models often fail to predict human-specific responses. Organs on chips offer a promising alternative, but widespread use of polydimethylsiloxane introduces challenges due to its sorption of small lipophilic molecules, distorting pharmacokinetic and pharmacodynamic data. Cyclic olefin copolymer, a chemically stable alternative with minimal sorption, has emerged as a potential solution. This study investigates the sorption behavior of seven pharmaceutically active compounds in microfluidic devices and washout of these compounds, using high-performance liquid chromatography-mass spectrometry to evaluate recovery of compounds. Lipophilic molecules exhibited substantial sorption in polydimethylsiloxane and lower retention in cyclic olefin copolymer. Imipramine (logP = 4.80) decreased from 100 µM to 0.0384 µM for polydimethylsiloxane and 31.5 µM for cyclic olefin copolymer after 24 h incubation. Sorption was governed by multiple factors - lipophilicity and rotatable bond count were critical for both materials, hydrogen bond acceptors and molecular weight played a larger role in cyclic olefin copolymer, whereas topological polar surface area was critical for polydimethylsiloxane. Washout studies revealed that polydimethylsiloxane retains lipophilic compounds through bulk absorption, causing slow release, while cyclic olefin copolymer facilitated easier desorption. The cumulative sum of the first 5 h washout of loperamide (logP = 5.13) is 37.8% for polydimethylsiloxane and 71.5% for cyclic olefin copolymer. These findings highlight the importance of material selection and molecular properties in minimizing sorption and ensuring reliable experimental outcomes especially in microfluidic systems with distinctly different surface to volume ratios to other models.
在药物研发中进行准确的风险评估至关重要，因为传统的体外和体内模型常常无法预测人类特有的反应。芯片上的器官提供了一种有前景的替代方案，但聚二甲基硅氧烷的广泛使用带来了挑战，因为它会吸附小分子亲脂性分子，从而扭曲药代动力学和药效学数据。环烯烃共聚物作为一种化学性质稳定、吸附极小的替代材料，已成为一种潜在的解决方案。本研究使用高效液相色谱 - 质谱法评估化合物的回收率，研究了七种药物活性化合物在微流控装置中的吸附行为以及这些化合物的洗脱情况。亲脂性分子在聚二甲基硅氧烷中表现出大量吸附，而在环烯烃共聚物中的保留率较低。在孵育24小时后，聚二甲基硅氧烷中的丙咪嗪（logP = 4.80）从100μM降至0.0384μM，环烯烃共聚物中的丙咪嗪降至31.5μM。吸附受多种因素影响——亲脂性和可旋转键数对两种材料都至关重要，氢键受体和分子量在环烯烃共聚物中起更大作用，而拓扑极性表面积对聚二甲基硅氧烷至关重要。洗脱研究表明，聚二甲基硅氧烷通过整体吸收保留亲脂性化合物，导致缓慢释放，而环烯烃共聚物则更容易解吸。对于洛哌丁胺（logP = 5.13），聚二甲基硅氧烷在最初5小时洗脱的累积总和为37.8%，环烯烃共聚物为71.5%。这些发现凸显了材料选择和分子性质在最小化吸附以及确保可靠实验结果方面的重要性，尤其是在与其他模型具有明显不同表面积与体积比的微流控系统中。
