A novel microfluidic mucus-chip for studying the permeation of compounds over the mucus barrier

Abstract

A major challenge of drug discovery is to overcome the mucus barrier, which is lined the surface of the gastrointestinal tract. The ability to overcome this barrier must be tested in preclinical in vitro models, prior to in vivo studies. Therefore, a microfluidic chip was developed to examine the possibility of compounds to overcome a mucus barrier. Native porcine intestinal mucus was used as a mucus model. The mucus was loaded inside the chip comprising of a microporous membrane and a fluidic compartment. To validate the system, caffeine as a hydrophilic positive compound, fluorescein isothiocyanate–dextran (FITC-dextran) as high molecular negative compound and diclofenac sodium as poorly permeating compound were tested. Test samples were applied on the surface of the mucus and samples were collected every 30 min from the fluidic compartment underneath the membrane. The permeation was measured over 3 h and the permeated compound was detected by high-pressure liquid chromatography (HPLC) and a microplate fluorescence reader. The results show that caffeine and diclofenac sodium are permeating over the mucus layer proportionally to the time. FITC-dextran, chosen as non-permeating compound, displays equivalently no permeation. The validation provides the functionality of the developed mucus-chip system.