A bespoke microfluidic pharmacokinetic compartment model for drug absorption using artificial cell membranes
| dc.contributor.author | Korner, Jaime L. | |
| dc.contributor.author | Stephenson, Elanna B. | |
| dc.contributor.author | Elvira, Katherine S. | |
| dc.date.accessioned | 2020-12-16T21:47:43Z | |
| dc.date.available | 2020-12-16T21:47:43Z | |
| dc.date.copyright | 2020 | en_US |
| dc.date.issued | 2020 | |
| dc.description.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. | en_US |
| dc.description.reviewstatus | Reviewed | en_US |
| dc.description.scholarlevel | Faculty | en_US |
| dc.description.sponsorship | This research was funded through the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant program. Dr. Elvira's position is funded through the Canada Research Chair program and her laboratory was equipped using funding from the Canada Foundation for Innovation John R. Evans Leaders Fund (CFI-JELF), the British Columbia Knowledge Development Fund (BCKDF) and the NSERC Research Tools and Instruments program. We also acknowledge Alberto Escobar Mingo for building the heating platform used in this work, and for writing the ESI† section detailing its performance. | en_US |
| dc.identifier.citation | Korner, J. L., Stephenson, E. B., & Elvira, K. S. (2020). Correction: A bespoke microfluidic pharmacokinetic compartment model for drug absorption using artificial cell membranes. Lab on a Chip, 20(11). https://doi.org/10.1039/d0lc00263a | en_US |
| dc.identifier.uri | https://doi.org/10.1039/d0lc90071k | |
| dc.identifier.uri | http://hdl.handle.net/1828/12454 | |
| dc.language.iso | en | en_US |
| dc.publisher | Lab on a Chip | en_US |
| dc.subject.department | Department of Chemistry | |
| dc.title | A bespoke microfluidic pharmacokinetic compartment model for drug absorption using artificial cell membranes | en_US |
| dc.type | Article | en_US |