Characterization of Drug-Polymer Adsorption Isotherms in Body-on-a-Chip Systems by Inverse Liquid-Solid Chromatography.

Abstract

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.