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Characterization of Drug–Polymer Adsorption Isotherms in Body-on-a-Chip Systems by Inverse Liquid–Solid Chromatography
ACS Biomaterials Science & Engineering ( IF 5.8 ) Pub Date : 2020-06-11 , DOI: 10.1021/acsbiomaterials.0c00350
Mark T. Schnepper 1 , Jeff Roles 2 , James J. Hickman 1, 2
Affiliation  

Body-on-a-chip and human-on-a-chip systems are currently being used to augment and could eventually replace animal models in drug discovery and basic biological research. However, hydrophobic molecules, especially therapeutic compounds, tend to adsorb to the polymer materials used to create these microfluidic platforms, which may distort the dose–response curves that feed into pharmacokinetic/pharmacodynamic (PK/PD) models, which translate preclinical data into predictions of clinical outcomes. Inverse liquid–solid chromatography paired with a numerical optimization based on the Langmuir model of adsorption was used to characterize the adsorption isotherm parameters of drugs to polydimethylsiloxane (PDMS) and polymethylmethacrylate (PMMA), polymers commonly used in these platforms. The adsorption isotherms were then compared against concentration measurements of drugs recirculated in these platforms. This research further illustrates the point that by quantifying drug or drug candidate interactions before system dosing and including this data in the PK/PD models, then polymers used in these platforms need not be limited to “less-adsorbing” materials.

中文翻译:

液相色谱法表征单芯片系统中药物-聚合物的吸附等温线

片上人体和片上人体系统目前正在被用来增强药物,并最终取代药物发现和基础生物学研究中的动物模型。但是,疏水分子,尤其是治疗性化合物,倾向于吸附到用于创建这些微流体平台的聚合物材料上,这可能会使输入到药代动力学/药效学(PK / PD)模型中的剂量反应曲线扭曲,从而将临床前数据转化为预测临床结果。液相-固相​​色谱结合基于Langmuir吸附模型的数值优化方法,用于表征药物对聚二甲基硅氧烷(PDMS)和聚甲基丙烯酸甲酯(PMMA)的吸附等温线参数,这些平台通常使用聚合物。然后将吸附等温线与在这些平台中循环的药物浓度进行比较。这项研究进一步说明了这一点,即通过在系统加药之前量化药物或候选药物的相互作用并将此数据包括在PK / PD模型中,则这些平台中使用的聚合物不必局限于“吸收较少”的材料。
更新日期:2020-08-10
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