Small molecule absorption by PDMS in the context of drug response bioassays.
Small molecule absorption by PDMS in the context of drug response bioassays.
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DOI：
10.1016/j.bbrc.2016.11.062
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发表时间：
2017-01-08
影响因子：
3.1
通讯作者：
Mummery CL
中科院分区：
文献类型：
--
作者：
van Meer BJ;de Vries H;Firth KSA;van Weerd J;Tertoolen LGJ;Karperien HBJ;Jonkheijm P;Denning C;IJzerman AP;Mummery CL
聚合物聚二甲基硅氧烷（PDMS）被广泛用于构建与细胞培养相容的微流体装置。虽然制造方便，但PDMS的缺点是它可以吸收小分子，如药物。在像“芯片器官”这样的微流体设备中，旨在检查细胞行为并测试药物的效果，这可能会影响药物的生物利用度。在这里，我们开发了一种测定方法，通过高压液相色谱法（HPLC）测量残留的未吸收化合物，比较PDMS对一组测试的四种心脏药物的吸收。我们发现，吸收是可变的和时间依赖性的，而不是如前所述的疏水性决定的。我们证明了两种市售的亲脂性涂层和细胞的存在影响吸收。亲脂性涂层的使用可用于防止小分子被PDMS吸收。不同化合物与PDMS的结合变化很大。不能重复先前报道的吸收和LogP值的相关性。拓扑极性表面积可能与化合物吸收有关。基于脂质的涂层部分地避免了化合物吸收。培养细胞的存在影响游离药物浓度，但小于底物。
The polymer polydimethylsiloxane (PDMS) is widely used to build microfluidic devices compatible with cell culture. Whilst convenient in manufacture, PDMS has the disadvantage that it can absorb small molecules such as drugs. In microfluidic devices like “Organs-on-Chip”, designed to examine cell behavior and test the effects of drugs, this might impact drug bioavailability. Here we developed an assay to compare the absorption of a test set of four cardiac drugs by PDMS based on measuring the residual non-absorbed compound by High Pressure Liquid Chromatography (HPLC). We showed that absorption was variable and time dependent and not determined exclusively by hydrophobicity as claimed previously. We demonstrated that two commercially available lipophilic coatings and the presence of cells affected absorption. The use of lipophilic coatings may be useful in preventing small molecule absorption by PDMS. Binding of different compounds to PDMS varies greatly. Previous reported correlations of absorption and LogP values could not be repeated. Topological polar surface area possibly related to compound absorption. A lipid based coating partially obviates compound absorption. Presence of cultured cells affects free drug concentration, but less than substrate.