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An integrated microfluidic platform for quantifying drug permeation across biomimetic vesicle membranes

By Michael Schaich, Jehangir Cama, Kareem Al Nahas, Diana Sobota, Kevin Jahnke, Siddharth Deshpande, Cees Dekker, Ulrich F. Keyser

Posted 17 Jan 2019
bioRxiv DOI: 10.1101/523431 (published DOI: 10.1021/acs.molpharmaceut.9b00086)

The low membrane permeability of candidate drug molecules is a major challenge in drug development and insufficient permeability is one reason for the failure of antibiotic treatment against bacteria. Quantifying drug transport across specific pathways in living systems is challenging since one typically lacks knowledge of the exact lipidome and proteome of the individual cells under investigation. Here, we quantify drug permeability across biomimetic liposome membranes, with comprehensive control over membrane composition. We integrate the microfluidic octanol-assisted liposome assembly platform with an optofluidic transport assay to create a complete microfluidic total analysis system for quantifying drug permeability. Our system enables us to form liposomes with charged lipids mimicking the negative charge of bacterial membranes at physiological salt and pH levels, which proved difficult with previous liposome formation techniques. Furthermore, the microfluidic technique yields an order of magnitude more liposomes per experiment than previous assays. We demonstrate the feasibility of the assay by determining the permeability coefficient of norfloxacin across biomimetic liposomes.

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