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Application of perfluoropolyether elastomers in microfluidic drug metabolism assays
Open accessAbstract
Recently, increasing attention has been paid to liver-on-a-chip models for both pharmacokinetics and toxicity (ADMET) screenings. Although polydimethylsiloxane (PDMS) is the most popular material for the fabrication of microfluidic devices, its extensive sorption of hydrophobic drugs limits its applications. Therefore, we investigated a chemically repellent material, perfluoropolyether (PFPE) elastomer, as an alternative to PDMS. Primary rat hepatocytes cultured in the PFPE microfluidic device were polygonal or cuboidal in shape and had one or two prominent nuclei, as when cultured in 96-well plates. When hepatocytes were cultured in the PFPE microfluidic device and exposed to dynamic flow, the production of albumin and urea increased 3.94- and 1.72-fold, respectively, compared with no dynamic flow. Exposure to dynamic flow did not result in obvious changes in the expression of cytochrome P450, but increased the metabolic activity of hepatocytes compared to under static conditions. PFPE devices did not absorb midazolam, which was extensively absorbed by PDMS devices. However, the sorption of bufuralol could not be avoided even with PFPE devices. Solvent swelling experiments highlighted much better chemical repellency with PFPE than with PDMS. Hansen solubility parameters and sphere radius were estimated from the solvent swelling experiments. The relative energy distance (RED) of bufuralol to PFPE was much smaller than that of other three drugs tested, reasonably explaining the high sorption of bufuralol to PFPE. Although sorption into PFPE cannot be completely avoided, PFPE microfluidic devices may provide a better performance in ADMET evaluation than PDMS.
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Fluoropolymers and perfluoropolyether oils have not been linked to any adverse effects on humans but have rather improved quality of life and well-being.
“These materials have not been linked to any adverse effects on humans but have rather improved quality of life and well-being.”
From The EU’s Per- and Polyfluoroalkyl Substances (PFAS) Ban: A Case of Policy over Science (2023) · cites this paper as [8]
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Metadata
- Authors
- Wang, M., Tsuda, M., Deguchi, S., Higuchi, Y., So, K., Torisawa, Y.-S., Takayama, K., & Yamashita, F.
- Affiliations
- Kyoto University (JP)
- Corresponding author
- Yamashita, Fumiyoshi
- Venue
- International Journal of Pharmaceutics
- Publisher
- Elsevier BV
- Published
- 2022-11
- Volume
- 627
- Pages
- 122253
- ISSN
- 0378-5173 (ISSN-L)
- OpenAlex
- W4297963427
- Cited by
- 10
- References
- 34
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 3
- FWCI
- 0.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 332 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- International Journal of Pharmaceutics (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Agency for Medical Research and Development (jp21be0304202h0005)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Bio-sensing Technologies
- Keywords
- liver-on-a-chip, hepatocyte culture, drug sorption, solvent swelling, Hansen solubility parameters, bufuralol, midazolam, cytochrome P450 expression, ADMET screening
- MeSH terms
- Albumins, Animals, Dimethylpolysiloxanes, Ethers, Fluorocarbons, Midazolam, Solvents, Urea, Elastomers, Microfluidics, Rats
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