Drug permeability assay using microhole-trapped cells in a microfluidic device

Area of Science:

• Biomedical Engineering
• Pharmacology
• Drug Discovery

Background:

• Oral drug absorption necessitates intestinal permeability assessment in early drug discovery.
• Existing methods may not fully replicate the in vivo drug delivery pathway.

Purpose of the Study:

• To develop and validate a microfluidic device for drug permeability assays that mimics the intestinal environment.
• To assess the correlation of this device's results with in vivo human and rat intestinal permeability.

Main Methods:

• Fabrication of a microfluidic device with a poly(dimethylsiloxane) (PDMS) microhole array for cell trapping.
• Optimization of device configuration using mathematical simulations for stable cell trapping.
• Measurement of permeability for 10 drugs and comparison with in vivo data.

Main Results:

• The microfluidic device successfully trapped intestinal epithelial cells without damage.
• Measured drug permeabilities showed high correlation with human (R²=0.9013) and rat (R²=0.8765) in vivo data.
• The device's measurements strongly correlated with the fraction of dose absorbed in humans (R²=0.9641).

Conclusions:

• The developed microfluidic device serves as a valuable tool for drug discovery.
• This system provides a reliable alternative to animal testing for drug permeability evaluation.
• The device accurately predicts in vivo drug absorption characteristics.