Intestinal explant barrier chip: long-term intestinal absorption screening in a novel microphysiological system using...

Area of Science:

• Pharmacology
• Biotechnology
• Drug Discovery

Background:

• Current in vitro intestinal models lack complexity, hindering accurate drug absorption prediction.
• Tissue explants offer biological relevance but suffer from limited viability in static cultures.

Purpose of the Study:

• To develop a microphysiological system, the Intestinal Explant Barrier Chip (IEBC), for enhanced intestinal tissue viability and drug absorption screening.
• To assess the functionality, integrity, and viability of human and porcine colon tissue explants within the IEBC over 24 hours.

Main Methods:

• Incorporation of human and porcine colon tissue explants into a microfluidic chip using a snap-fit mechanism.
• Dynamic microenvironment creation within the IEBC to sustain tissue viability.
• Assessment of transcellular vs. paracellular transport, FITC-dextran leakage, and intracellular lactate dehydrogenase levels.
• Drug permeability ranking using a panel of drugs with varying permeability.

Main Results:

• The IEBC successfully maintained tissue functionality, integrity, and viability for 24 hours.
• A transcellular to paracellular transport ratio greater than 2 indicated good tissue functionality.
• Low FITC-dextran leakage and preserved intracellular lactate dehydrogenase confirmed tissue integrity and viability.
• 6 out of 7 drugs were accurately ranked by their fraction absorbed, demonstrating predictive potential.

Conclusions:

• The Intestinal Explant Barrier Chip (IEBC) is a novel, medium-throughput screening platform.
• The IEBC leverages the complexity of tissue explants and the benefits of microfluidic flow.
• This system offers improved prediction of intestinal drug absorption compared to traditional in vitro models.