As most medicines are given orally, it is important to study what happens to new drugs upon ingestion. A better, more representative and more efficient model of the human gastrointestinal (GI) tract is required for these studies than used today. This thesis describes novel methods to test the behavior of drugs in the human GI tract based on continuously flowing microsystems. In order to reach the desired site of action, drug molecules must first survive the harsh conditions in the GI tract. Samples containing drugs or foods were exposed to artificial versions of digestive juices in micromixers to study the effects of digestion on the samples. The digested samples then reached a gut-on-a-chip – a miniaturized model of the human intestinal barrier – to study the absorption of drugs across a layer of living intestinal cells into the body compartment. This uptake process was studied using state-of-the-art analytical-chemical techniques such as mass spectrometry. Two different model drugs were studied in this system, with one drug clearly broken down by the preceding digestion. The second part of this thesis describes different novel methods and equipment for use in such gut-on-a-chip systems, including a control system to deliver liquids to organs-on-chips for longer experiments (days), new microfabrication strategies to produce very thin, porous membranes to serve as support for the gut-on-a-chip barriers, and 3D-printed components for use in microfluidic digestive systems. It is envisioned that the work described in this thesis may contribute to faster and more efficient studies of novel drugs and foods.
|Kwalificatie||Doctor of Philosophy|
|Datum van toekenning||19-nov.-2021|
|Plaats van publicatie||[Groningen]|
|Status||Published - 2021|