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Passive Membrane Transport Analysis of Drug Mixtures
Robert Strutt1, Simon F Berlanda1, Petra S Dittrich1
1Department of Biosystems Science and Engineering, ETH Zürich, Schanzenstrasse 44, 4056 Basel, Switzerland.
Analytical Chemistry
|August 5, 2025
Summary
This study introduces a new HPLC-MS method using droplet interface bilayers (DIBs) to analyze drug mixtures and their membrane transport. The findings reveal correlations between drug properties and permeability, aiding pharmaceutical design.
Area of Science:
- Biochemistry
- Pharmacology
- Materials Science
Background:
- Membrane transport is crucial for cells and drug development.
- Existing in vitro methods often use non-biomimetic interfaces and analyze single compounds.
- Biomimetic membranes offer advanced strategies for studying cellular processes.
Purpose of the Study:
- To develop and validate an in vitro, label-free method for analyzing drug mixtures and their membrane transport mechanisms.
- To classify the permeability of diverse FDA-approved drugs using a novel approach.
- To investigate the influence of physiological variables on drug transport across biomimetic membranes.
Main Methods:
- Development of a droplet interface bilayer (DIB) method coupled with High-Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS).
- Analysis of drug mixtures to assess simultaneous membrane transport.
- Classification of drug permeability based on in vitro transport data.
Main Results:
- Established a novel HPLC-MS, DIB method for drug mixture analysis and transport mechanism delineation.
- Correlated drug permeability classifiers with properties like hydrophobicity, hydrogen bonding, lipophilicity, and predicted gut absorption.
- Quantified passive transport under physiological conditions (pH, temperature, lipid composition) and identified coexisting facilitated and simple diffusion in the presence of proteins.
Conclusions:
- Droplet interface bilayers (DIBs) provide physiologically relevant interfaces for drug transport studies.
- The developed method is effective for classifying drug permeability and understanding transport mechanisms.
- This approach has significant implications for artificial cell systems and high-throughput drug screening.
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