Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Gut-on-a-Chip Research for Drug Development: Implications of Chip Design on Preclinical Oral Bioavailability or Intestinal Disease Studies

Version 1 : Received: 1 May 2023 / Approved: 2 May 2023 / Online: 2 May 2023 (01:15:08 CEST)

A peer-reviewed article of this Preprint also exists.

Donkers, J.M.; van der Vaart, J.I.; van de Steeg, E. Gut-on-a-Chip Research for Drug Development: Implications of Chip Design on Preclinical Oral Bioavailability or Intestinal Disease Studies. Biomimetics 2023, 8, 226. Donkers, J.M.; van der Vaart, J.I.; van de Steeg, E. Gut-on-a-Chip Research for Drug Development: Implications of Chip Design on Preclinical Oral Bioavailability or Intestinal Disease Studies. Biomimetics 2023, 8, 226.

Abstract

The gut plays a key role in drug absorption and metabolism of orally ingested drugs. Additionally, characterization of intestinal disease processes are increasingly gaining more attention as gut health is an important contributor to our overall health. The most recent innovation to study intestinal processes in vitro is the development of gut-on-a-chip (GOC) systems. Compared to conventional in vitro models they offer more translational value, and many different GOC models have been presented over the past years. Here, we reflect on the almost unlimited choices in designing and selecting a GOC for preclinical drug (or food) development research. Four components that largely influence the GOC design are highlighted, namely 1) the biological research questions, 2) chip fabrication and materials, 3) tissue engineering, and 4) the environmental and biochemical cues to add or measure in the GOC. Examples are presented of GOC studies in the two major areas of preclinical intestinal research: 1) intestinal absorption and metabolism to study the oral bioavailability of compounds, and 2) treatment-orientated research for intestinal diseases. The last section of this review presents an outlook on the limitations to overcome in order to accelerate preclinical GOC research.

Keywords

organ-on-a-chip; gut-on-a-chip; intestine; in vitro; ex vivo; ADME; oral bioavailability; drug development; microbiome; IBD

Subject

Biology and Life Sciences, Cell and Developmental Biology

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