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Issue 11, 2020
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A bespoke microfluidic pharmacokinetic compartment model for drug absorption using artificial cell membranes

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Abstract

Early prediction of the rate and extent of intestinal absorption is vital for the efficient development of orally administered drugs. Here we show a new type of pharmacokinetic compartment model that shows a threefold improvement in the prediction of molecular absorption in the jejunum than the current state-of-the-art in vitro technique, parallel artificial membrane permeability assays (PAMPA). Our three-stage pharmacokinetic compartment model uses microfluidic droplets and bespoke, biomimetic artificial cells to model the path of a drug proxy from the intestinal space into the blood via an enterocyte. Each droplet models the buffer and salt composition of each pharmacokinetic compartment. The artificial cell membranes are made from the major components of human intestinal cell membranes (L-α-phosphatidylcholine, PC and L-α-phosphatidylethanolamine, PE) and sizes are comparable to human cells (∼0.5 nL). We demonstrate the use of the microfluidic platform to quantify common pharmacokinetic parameters such as half-life, flux and the apparent permeability coefficient (Papp). Our determined Papp more closely resembles that of actual intestinal tissue than PAMPA, which overestimates it by a factor of 20.

Graphical abstract: A bespoke microfluidic pharmacokinetic compartment model for drug absorption using artificial cell membranes

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Supplementary files

Article information


Submitted
13 Mar 2020
Accepted
04 Apr 2020
First published
07 Apr 2020

Lab Chip, 2020,20, 1898-1906
Article type
Paper

A bespoke microfluidic pharmacokinetic compartment model for drug absorption using artificial cell membranes

J. L. Korner, E. B. Stephenson and K. S. Elvira, Lab Chip, 2020, 20, 1898
DOI: 10.1039/D0LC00263A

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