Related Experiment Video
Updated: Jul 12, 2025
10:05
The Multi-organ Chip - A Microfluidic Platform for Long-term Multi-tissue Coculture
Published on: April 28, 2015
28.8K
A Novel Milli-fluidic Liver Tissue Chip with Continuous Recirculation for Predictive Pharmacokinetics Applications.
Shiny Amala Priya Rajan1, Jason Sherfey1, Shivam Ohri1
1Javelin Biotech Inc, 299 Washington street, Woburn, Massachusetts, 01801, USA.
The AAPS Journal
|October 27, 2023
Summary
A novel milli-fluidic liver tissue chip (LTC) improves drug development by accurately predicting hepatic clearance. This bioengineered platform offers sustained cultures and reliable in vitro-in vivo correlation for drug pharmacokinetic studies.
Area of Science:
- Drug development and pharmacokinetics
- Bioengineering and microfluidics
- Hepatology and drug metabolism
Background:
- Accurate hepatic clearance estimation is vital for drug development but current in vitro methods lack physiological relevance and long-term stability.
- Limitations include short incubation times, non-physiological conditions, drug-binding materials, and evaporation, hindering reliable pharmacokinetic predictions.
Purpose of the Study:
- To develop and characterize a novel milli-fluidic liver tissue chip (LTC) for improved in vitro hepatic clearance assessment.
- To demonstrate the LTC's ability to accurately predict pharmacokinetic parameters for both low- and high-clearance drugs.
- To establish a physiologically relevant platform for long-term drug metabolism and pharmacokinetic studies.
Main Methods:
- Development of a milli-fluidic liver tissue chip (LTC) using cyclic olefin copolymer (COC) with continuous media recirculation.
- Characterization of the LTC for non-specific binding, evaporation, and drug absorption properties.
- Culturing of human primary hepatocytes within the LTC for sustained metabolic activity and polarization over 15 days.
- Assessment of drug clearance for various compounds over 12 days, evaluating in vitro-in vivo correlation (IVIVC).
Main Results:
- The COC-based LTC demonstrated negligible evaporation and minimal non-specific drug binding.
- Sustained hepatic culture showed functional polarization and metabolic CYP activity for at least 15 days.
- Accurate prediction of pharmacokinetic parameters for low- and high-clearance compounds was achieved with high IVIVC.
- LTC performance was unaffected by rifampicin induction or culture age, showing consistent depletion kinetics.
Conclusions:
- The novel milli-fluidic liver tissue chip (LTC) provides a reproducible and reliable platform for physiologically relevant in vitro hepatic clearance studies.
- This bioengineered solution addresses key technological limitations of current methods, enabling more accurate drug pharmacokinetic predictions.
- The LTC platform supports long-term hepatic cultures, crucial for understanding drug metabolism and improving lead selection in drug development.
