Assessment of drug permeability using a small airway microphysiological system

Area of Science:

• Pharmacology
• Biotechnology
• Drug Delivery

Background:

• Accurate prediction of inhaled drug permeability is crucial for new and generic drug development.
• Traditional 2D cell cultures lack the physiological relevance of lung microenvironments.
• A small airway microphysiological system (MPS) offers a more accurate in vitro model.

Purpose of the Study:

• To evaluate a small airway MPS for measuring inhaled drug permeability.
• To assess the system's ability to recapitulate the pulmonary air-liquid interface (ALI).

Main Methods:

• Primary human lung epithelial cells cultured at ALI, followed by endothelial cell co-culture.
• Non-specific binding of drugs to the polydimethylsiloxane (PDMS) material was quantified.
• Drug permeability was measured by quantifying compound passage over time.

Main Results:

• The MPS successfully replicated lung cell types and morphology.
• Albuterol sulfate, formoterol fumarate, and olodaterol HCl showed insignificant non-specific binding.
• Fluticasone furoate exhibited significant non-specific binding and was excluded.
• Apparent permeability (Papp) values were determined for each compound.

Conclusions:

• The small airway MPS provides a physiologically relevant model for inhaled drug permeability.
• Albuterol sulfate and formoterol fumarate are highly permeable; olodaterol HCl is low permeable.
• This MPS can improve the prediction of inhaled drug behavior in vivo.