Usability of Polydimethylsiloxane-Based Microfluidic Devices in Pharmaceutical Research Using Human Hepatocytes

Area of Science:

• Biotechnology
• Pharmacology
• Microfluidics

Background:

• Liver-on-a-chip (liver-chip) devices utilize microfluidics and liver cells to mimic liver function.
• Polydimethylsiloxane (PDMS) is a common material for these devices, but its hydrophobicity can lead to drug absorption.
• Understanding drug absorption and cellular response in PDMS-based liver-chips is crucial for reliable drug discovery.

Purpose of the Study:

• To evaluate drug absorption rates into PDMS microfluidic devices.
• To investigate the drug responsiveness of human hepatocytes cultured within these PDMS devices (hepatocyte-chips).
• To assess the utility of PDMS-based liver-chips for drug discovery research.

Main Methods:

• Measured the absorption rates of 12 model compounds into PDMS devices.
• Correlated absorption rates with the octanol/water distribution coefficient (log D) of the compounds.
• Utilized hepatocyte-chips to assess cellular responses to known hepatic function-modulating drugs.

Main Results:

• Significant absorption of certain compounds (midazolam, bufuralol, cyclosporine A, verapamil) into PDMS was observed.
• Drug absorption rates strongly correlated with their log D values (R² = 0.76).
• Hepatocyte-chips successfully demonstrated responsiveness to drug treatments, including cytochrome P450 (CYP) inducers and farnesoid X receptor (FXR) ligands.

Conclusions:

• PDMS-based liver-chips exhibit significant drug absorption, particularly for lipophilic compounds.
• Despite absorption, these hepatocyte-chips remain responsive to key drug classes, validating their use.
• Findings support the application of PDMS liver-chips in preclinical drug discovery and development.