An Open-Access Dialysis Membrane-Integrated Microfluidic Device for Generating Drug Exposure Profiles Through...

Area of Science:

• Biomedical Engineering
• Pharmacology
• Cell Biology

Background:

• Conventional in vitro assays and microphysiological systems face challenges in creating time-dependent drug exposure profiles.
• Simultaneous medium replacement in these systems often removes or reintroduces drugs, complicating controlled exposure.

Purpose of the Study:

• To develop an Open-access Dialysis Membrane-integrated Microfluidic Device (O-DMiMD) for precise control over drug exposure timing.
• To decouple nutrient supply from drug exposure control using molecular weight-dependent transport.

Main Methods:

• Designed a microfluidic device with a cell culture compartment (CCC) and a donor compartment (DC) separated by a dialysis membrane.
• Evaluated transport of Lucifer Yellow, FITC-dextran, and glucose across the membrane.
• Conducted drug-response studies using SN-38 and T-DM1 in co-culture models under varied medium change conditions.

Main Results:

• Lucifer Yellow and glucose permeated the dialysis membrane; FITC-dextran was retained.
• The O-DMiMD maintained co-culture proliferation and enabled time-dependent drug exposure profiles for SN-38.
• Different SK-BR-3 responses were observed for T-DM1 based on exposure conditions, indicating molecular weight-dependent effects.

Conclusions:

• The O-DMiMD offers an open-access platform for in vitro drug response evaluation.
• This device allows drug response assessment under exposure profiles influenced by molecular weight, protein binding, and cellular metabolism.
• The O-DMiMD facilitates studies on time-dependent drug effects and complex pharmacokinetic/pharmacodynamic relationships.