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A Gut/Liver microphysiological system for profiling human oral bioavailability
Explore how the innovative Gut/Liver microphysiological system (MPS) enhances in vitro ADME profiling by linking primary human intestinal and liver cells to predict human drug bioavailability more accurately. This webinar demonstrates improved predictive capacity for complex drug behaviors, advancing drug discovery and safety assessment.
ADME studies are a key part of drug discovery, as the evaluation of pharmacological properties determines the efficacy and safety of a given compound. Efforts to improve the in vitro to in vivo translation of drug efficacy and safety data has led to the emergence of more complex microphysiological systems (MPS) that consist of multiple organs that are fluidically linked.
During our webinar, we will introduce a Gut/Liver MPS (also known as a Gut/Liver-on-a-chip) and demonstrate that intestinal barrier integrity (RepliGut® – Planar Jejunum) and hepatic metabolic functionality (primary human hepatocyte) are maintained when cultured under perfusion using the PhysioMimix® Multi-organ System.
We will highlight the use of this dual-organ MPS in our PhysioMimix Bioavailability assay. The assay enables the simulation of IV and oral dosing routes to assess the individual and combined effects of human jejunum and liver models for human bioavailability profiling.
To demonstrate the assay’s improved predictive capacity, we investigated two drugs where current models fail to predict human ADME behaviour: Temocapril, which is a prodrug and is designed to be resistant to intestinal hydrolysis and Midazolam, which is known to undergo intestinal clearance.
Using these well-studied compounds, we show that the primary Gut/Liver MPS more precisely recapitulates the human process of intestinal absorption, intestinal metabolism, and hepatic clearance compared to traditional approaches operating in isolation.
Learning Objectives:
- Learn how to model the Gut/Liver axis for ADME studies with the PhysioMimix Gut/Liver MPS
- Learn how RepliGut® – Planar Jejunum recapitulates the human small intestine
- Use of the assay to profile human oral bioavailability
- Understand the predictive potential of the assay for drug ADME and bioavailability studies
About the Presenters
Yassen
Dr. Yassen Abbas is a Lead Scientist at CN Bio. He completed an MEng in chemical engineering at The University of Edinburgh and joined the European Space Agency as a graduate engineer. He later received a PhD from the University of Cambridge and completed a postdoc fellowship, also at Cambridge on the development of a tissue engineered model of the human endometrium. He has experience with real-time sensor technology, organoids and development of in vitro tissue models using human primary cells. Dr Abbas has published five peer-reviewed scientific articles, four as first author.
Liz
Dr. Elizabeth (Liz) Boazak is the Associate Director of R&D at Altis Biosystems. She completed a PhD in biomedical engineering at The City College of New York (CCNY) and a postdoc at the Georgia Institute of Technology, with a focus on biomechanics and biomaterials for tissue engineering and in vitro model systems development. Dr. Boazak worked at KBI Biopharma in cell line development prior to joining Altis where she oversees development of advanced in vitro models of the human intestinal epithelium.