Leakiness and Size Exclusion of Paracellular Channels in Cultured Epithelial Cell Monolayers-Interlaboratory Comparison
Purpose To determine and compare the paracellular characteristics of permeability (Papp) of Caco-2, MDCK, and 2/4/A1 cell lines. Methods The Papp data from 14 studies were analyzed by weighted nonlinear regression in terms of the paracellular parameters: porosity-pathlength (ε/δ), pore radius (R), a...
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| description | Purpose To determine and compare the paracellular characteristics of permeability (Papp) of Caco-2, MDCK, and 2/4/A1 cell lines. Methods The Papp data from 14 studies were analyzed by weighted nonlinear regression in terms of the paracellular parameters: porosity-pathlength (ε/δ), pore radius (R), and electrostatic potential drop (Δφ). Aqueous diffusivities, Daq, for the analysis, were empirically determined. The required hydrodynamic radii, rHYD, were estimated without knowledge of compound density. Mannitol iso-paracellular profiles allowed comparisons of “leakiness” across labs. Results Daq (37°C) was predicted as 9.9 × 10⁻⁵ MW⁻⁰.⁴⁵³; rHYD = (0.92 + 21.8 MW⁻¹)·rSE, where rSE is the Stokes-Einstein radius. Values of pore radius ranged from 4.0(±0.1) to 18(±3) Å, with the 2/4/A1 indicating the largest pores. The ε/δ capacity factor ranged from 0.2 (±0.1) to 69 (±5) cm⁻¹, with most values |
| doi_str_mv | 10.1007/s11095-009-0036-7 |
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Methods The Papp data from 14 studies were analyzed by weighted nonlinear regression in terms of the paracellular parameters: porosity-pathlength (ε/δ), pore radius (R), and electrostatic potential drop (Δφ). Aqueous diffusivities, Daq, for the analysis, were empirically determined. The required hydrodynamic radii, rHYD, were estimated without knowledge of compound density. Mannitol iso-paracellular profiles allowed comparisons of “leakiness” across labs. Results Daq (37°C) was predicted as 9.9 × 10⁻⁵ MW⁻⁰.⁴⁵³; rHYD = (0.92 + 21.8 MW⁻¹)·rSE, where rSE is the Stokes-Einstein radius. Values of pore radius ranged from 4.0(±0.1) to 18(±3) Å, with the 2/4/A1 indicating the largest pores. The ε/δ capacity factor ranged from 0.2 (±0.1) to 69 (±5) cm⁻¹, with most values <1.5 cm⁻¹. The average potential drop for Caco-2 models was Δφ wt avg Caco⁻² = −43 ± 20 mV. The paracellular model predicted measured log Papp values with pooled r ² = 0.93 and s = 0.17 (n = 108). Conclusion R and ε/δ are negatively correlated to a large extent. Papp can be rate-limited by either factor, with a wide range of possible combinations still indicating nearly constant leakiness for a given marker.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1007/s11095-009-0036-7</identifier><identifier>PMID: 20069445</identifier><identifier>CODEN: PHREEB</identifier><language>eng</language><publisher>Boston: Boston : Springer US</publisher><subject>Animals ; Biochemistry ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedical Engineering and Bioengineering ; Biomedicine ; Caco-2 Cells ; Cell Line ; Cell Membrane Permeability ; Diffusion ; Epithelial Cells - metabolism ; General pharmacology ; Humans ; Medical Law ; Medical sciences ; Pharmaceutical Preparations - chemistry ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacokinetics ; Pharmacology. Drug treatments ; Pharmacology/Toxicology ; Pharmacy ; Research Paper</subject><ispartof>Pharmaceutical research, 2010-03, Vol.27 (3), p.480-489</ispartof><rights>Springer Science+Business Media, LLC 2010</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c490t-eef9b608a5f1dc0f9a251a270c5d9a1b3a2d3d7c27db330a9c515971d4cbf9033</citedby><cites>FETCH-LOGICAL-c490t-eef9b608a5f1dc0f9a251a270c5d9a1b3a2d3d7c27db330a9c515971d4cbf9033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11095-009-0036-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11095-009-0036-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22651141$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20069445$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Avdeef, Alex</creatorcontrib><title>Leakiness and Size Exclusion of Paracellular Channels in Cultured Epithelial Cell Monolayers-Interlaboratory Comparison</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><addtitle>Pharm Res</addtitle><description>Purpose To determine and compare the paracellular characteristics of permeability (Papp) of Caco-2, MDCK, and 2/4/A1 cell lines. Methods The Papp data from 14 studies were analyzed by weighted nonlinear regression in terms of the paracellular parameters: porosity-pathlength (ε/δ), pore radius (R), and electrostatic potential drop (Δφ). Aqueous diffusivities, Daq, for the analysis, were empirically determined. The required hydrodynamic radii, rHYD, were estimated without knowledge of compound density. Mannitol iso-paracellular profiles allowed comparisons of “leakiness” across labs. Results Daq (37°C) was predicted as 9.9 × 10⁻⁵ MW⁻⁰.⁴⁵³; rHYD = (0.92 + 21.8 MW⁻¹)·rSE, where rSE is the Stokes-Einstein radius. Values of pore radius ranged from 4.0(±0.1) to 18(±3) Å, with the 2/4/A1 indicating the largest pores. The ε/δ capacity factor ranged from 0.2 (±0.1) to 69 (±5) cm⁻¹, with most values <1.5 cm⁻¹. The average potential drop for Caco-2 models was Δφ wt avg Caco⁻² = −43 ± 20 mV. The paracellular model predicted measured log Papp values with pooled r ² = 0.93 and s = 0.17 (n = 108). Conclusion R and ε/δ are negatively correlated to a large extent. Papp can be rate-limited by either factor, with a wide range of possible combinations still indicating nearly constant leakiness for a given marker.</description><subject>Animals</subject><subject>Biochemistry</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering and Bioengineering</subject><subject>Biomedicine</subject><subject>Caco-2 Cells</subject><subject>Cell Line</subject><subject>Cell Membrane Permeability</subject><subject>Diffusion</subject><subject>Epithelial Cells - metabolism</subject><subject>General pharmacology</subject><subject>Humans</subject><subject>Medical Law</subject><subject>Medical sciences</subject><subject>Pharmaceutical Preparations - chemistry</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacokinetics</subject><subject>Pharmacology. Drug treatments</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacy</subject><subject>Research Paper</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kMFu1DAQhi0EokvhAbiAhcQxMGMn8fqIogUqLQKpVOJmTRynTfHai50IlqfH1S70xsHywd__z_hj7DnCGwRQbzMi6KYC0OXItlIP2AobJSsN9beHbAVK1NVa1XjGnuR8CwBr1PVjdiYAWl3XzYr93Dr6PgWXM6cw8Mvpt-ObX9YveYqBx5F_oUTWeb94Sry7oRCcz3wKvFv8vCQ38M1-mm-cn8jzroD8UwzR08GlXF2E2SVPfUw0x3TgXdztKU05hqfs0Ug-u2en-5xdvd987T5W288fLrp328rWGubKuVH3LaypGXGwMGoSDZJQYJtBE_aSxCAHZYUaeimBtG2w0QqH2vajBinP2atj7z7FH4vLs7mNSwplpCleoJVa6ALhEbIp5pzcaPZp2lE6GARzZ9ocTZti2tyZNqpkXpyKl37nhn-Jv2oL8PoEULbkx0TBTvmeE22DWGPhxJHL5Slcu3S_4f-mvzyGRoqGrotSc3UpACXgurSWf_0BC_mg5g</recordid><startdate>20100301</startdate><enddate>20100301</enddate><creator>Avdeef, Alex</creator><general>Boston : Springer US</general><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>FBQ</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20100301</creationdate><title>Leakiness and Size Exclusion of Paracellular Channels in Cultured Epithelial Cell Monolayers-Interlaboratory Comparison</title><author>Avdeef, Alex</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c490t-eef9b608a5f1dc0f9a251a270c5d9a1b3a2d3d7c27db330a9c515971d4cbf9033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Biochemistry</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical Engineering and Bioengineering</topic><topic>Biomedicine</topic><topic>Caco-2 Cells</topic><topic>Cell Line</topic><topic>Cell Membrane Permeability</topic><topic>Diffusion</topic><topic>Epithelial Cells - metabolism</topic><topic>General pharmacology</topic><topic>Humans</topic><topic>Medical Law</topic><topic>Medical sciences</topic><topic>Pharmaceutical Preparations - chemistry</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacokinetics</topic><topic>Pharmacology. Drug treatments</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacy</topic><topic>Research Paper</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Avdeef, Alex</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Avdeef, Alex</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Leakiness and Size Exclusion of Paracellular Channels in Cultured Epithelial Cell Monolayers-Interlaboratory Comparison</atitle><jtitle>Pharmaceutical research</jtitle><stitle>Pharm Res</stitle><addtitle>Pharm Res</addtitle><date>2010-03-01</date><risdate>2010</risdate><volume>27</volume><issue>3</issue><spage>480</spage><epage>489</epage><pages>480-489</pages><issn>0724-8741</issn><eissn>1573-904X</eissn><coden>PHREEB</coden><abstract>Purpose To determine and compare the paracellular characteristics of permeability (Papp) of Caco-2, MDCK, and 2/4/A1 cell lines. Methods The Papp data from 14 studies were analyzed by weighted nonlinear regression in terms of the paracellular parameters: porosity-pathlength (ε/δ), pore radius (R), and electrostatic potential drop (Δφ). Aqueous diffusivities, Daq, for the analysis, were empirically determined. The required hydrodynamic radii, rHYD, were estimated without knowledge of compound density. Mannitol iso-paracellular profiles allowed comparisons of “leakiness” across labs. Results Daq (37°C) was predicted as 9.9 × 10⁻⁵ MW⁻⁰.⁴⁵³; rHYD = (0.92 + 21.8 MW⁻¹)·rSE, where rSE is the Stokes-Einstein radius. Values of pore radius ranged from 4.0(±0.1) to 18(±3) Å, with the 2/4/A1 indicating the largest pores. The ε/δ capacity factor ranged from 0.2 (±0.1) to 69 (±5) cm⁻¹, with most values <1.5 cm⁻¹. The average potential drop for Caco-2 models was Δφ wt avg Caco⁻² = −43 ± 20 mV. The paracellular model predicted measured log Papp values with pooled r ² = 0.93 and s = 0.17 (n = 108). Conclusion R and ε/δ are negatively correlated to a large extent. Papp can be rate-limited by either factor, with a wide range of possible combinations still indicating nearly constant leakiness for a given marker.</abstract><cop>Boston</cop><pub>Boston : Springer US</pub><pmid>20069445</pmid><doi>10.1007/s11095-009-0036-7</doi><tpages>10</tpages></addata></record> |
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| subjects | Animals Biochemistry Biological and medical sciences Biomedical and Life Sciences Biomedical Engineering and Bioengineering Biomedicine Caco-2 Cells Cell Line Cell Membrane Permeability Diffusion Epithelial Cells - metabolism General pharmacology Humans Medical Law Medical sciences Pharmaceutical Preparations - chemistry Pharmaceutical technology. Pharmaceutical industry Pharmacokinetics Pharmacology. Drug treatments Pharmacology/Toxicology Pharmacy Research Paper |
| title | Leakiness and Size Exclusion of Paracellular Channels in Cultured Epithelial Cell Monolayers-Interlaboratory Comparison |
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