A comparison of three mucus-secreting airway cell lines (Calu-3, SPOC1 and UNCN3T) for use as biopharmaceutical models of the nose and lung
[Display omitted] The aim of this work was to compare three existing mucus-secreting airway cell lines for use as models of the airways to study drug transport in the presence of mucus. Each cell line secreted mature, glycosylated mucins, evidenced by the enzyme-linked lectin assay. The secretagogue...
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| Veröffentlicht in: | European journal of pharmaceutics and biopharmaceutics 2021-10, Vol.167, p.159-174 |
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| creator | Lee, Diane F. Lethem, Michael I. Lansley, Alison B. |
| description | [Display omitted]
The aim of this work was to compare three existing mucus-secreting airway cell lines for use as models of the airways to study drug transport in the presence of mucus.
Each cell line secreted mature, glycosylated mucins, evidenced by the enzyme-linked lectin assay. The secretagogue, adenylyl-imidodiphosphate, increased mucin secretion in SPOC1 (3.5-fold) and UNCN3T (1.5-fold) cells but not in Calu-3 cells. In a novel mucus-depleted (MD) model the amount of mucus in the non-depleted wells was 3-, 8- and 4-fold higher than in the mucus-depleted wells of the Calu-3, SPOC1 and UNCN3T cells respectively. The permeability of 'high mucus’ cells to testosterone was significantly less in SPOC1 and UNCN3T cells (P |
| doi_str_mv | 10.1016/j.ejpb.2021.07.016 |
| format | Article |
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The aim of this work was to compare three existing mucus-secreting airway cell lines for use as models of the airways to study drug transport in the presence of mucus.
Each cell line secreted mature, glycosylated mucins, evidenced by the enzyme-linked lectin assay. The secretagogue, adenylyl-imidodiphosphate, increased mucin secretion in SPOC1 (3.5-fold) and UNCN3T (1.5-fold) cells but not in Calu-3 cells. In a novel mucus-depleted (MD) model the amount of mucus in the non-depleted wells was 3-, 8- and 4-fold higher than in the mucus-depleted wells of the Calu-3, SPOC1 and UNCN3T cells respectively. The permeability of 'high mucus’ cells to testosterone was significantly less in SPOC1 and UNCN3T cells (P < 0.05) but not Calu-3 cells.
Mucin secretion and cytokine release were investigated as indicators of drug irritancy in the SPOC1 and UNCN3T cell lines. A number of inhaled drugs significantly increased mucin secretion at high concentrations and the release of IL-6 and IL-8 from SPOC1 or UNCN3T cells (P < 0.05).
SPOC1 and UNCN3T cell lines are better able to model the effect of mucus on drug absorption than the Calu-3 cell line and are proposed for use in assessing drug-mucus interactions in inhaled drug and formulation development.</description><identifier>ISSN: 0939-6411</identifier><identifier>EISSN: 1873-3441</identifier><identifier>DOI: 10.1016/j.ejpb.2021.07.016</identifier><identifier>PMID: 34332033</identifier><language>eng</language><publisher>AMSTERDAM: Elsevier B.V</publisher><subject>Airway epithelial cells ; Animals ; Cell Line ; Cell-based assay ; Cytokines - metabolism ; Drug absorption ; Epithelial Cells - cytology ; Epithelial Cells - metabolism ; Humans ; Irritancy ; Life Sciences & Biomedicine ; Lung - cytology ; Lung - metabolism ; Mucin ; Mucins - metabolism ; Mucus - metabolism ; Mucus barrier ; Nasal drug delivery ; Nasal Mucosa - cytology ; Nasal Mucosa - metabolism ; Permeability barrier ; Pharmaceutical Preparations - administration & dosage ; Pharmaceutical Preparations - metabolism ; Pharmacology & Pharmacy ; Pulmonary drug delivery ; Rats ; Respiratory Mucosa - cytology ; Respiratory Mucosa - metabolism ; Science & Technology ; Testosterone ; Testosterone - metabolism</subject><ispartof>European journal of pharmaceutics and biopharmaceutics, 2021-10, Vol.167, p.159-174</ispartof><rights>2021</rights><rights>Copyright © 2021. Published by Elsevier B.V.</rights><rights>2021 The Authors. Published by Elsevier B.V. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>11</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000689599700006</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c455t-5b3d7b301344440ec36852a295b211e35e10c767eabd86c29e3491bad53497453</citedby><cites>FETCH-LOGICAL-c455t-5b3d7b301344440ec36852a295b211e35e10c767eabd86c29e3491bad53497453</cites><orcidid>0000-0002-1521-3725</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejpb.2021.07.016$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,315,782,786,887,3554,27933,27934,39267,46004</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34332033$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Diane F.</creatorcontrib><creatorcontrib>Lethem, Michael I.</creatorcontrib><creatorcontrib>Lansley, Alison B.</creatorcontrib><title>A comparison of three mucus-secreting airway cell lines (Calu-3, SPOC1 and UNCN3T) for use as biopharmaceutical models of the nose and lung</title><title>European journal of pharmaceutics and biopharmaceutics</title><addtitle>EUR J PHARM BIOPHARM</addtitle><addtitle>Eur J Pharm Biopharm</addtitle><description>[Display omitted]
The aim of this work was to compare three existing mucus-secreting airway cell lines for use as models of the airways to study drug transport in the presence of mucus.
Each cell line secreted mature, glycosylated mucins, evidenced by the enzyme-linked lectin assay. The secretagogue, adenylyl-imidodiphosphate, increased mucin secretion in SPOC1 (3.5-fold) and UNCN3T (1.5-fold) cells but not in Calu-3 cells. In a novel mucus-depleted (MD) model the amount of mucus in the non-depleted wells was 3-, 8- and 4-fold higher than in the mucus-depleted wells of the Calu-3, SPOC1 and UNCN3T cells respectively. The permeability of 'high mucus’ cells to testosterone was significantly less in SPOC1 and UNCN3T cells (P < 0.05) but not Calu-3 cells.
Mucin secretion and cytokine release were investigated as indicators of drug irritancy in the SPOC1 and UNCN3T cell lines. A number of inhaled drugs significantly increased mucin secretion at high concentrations and the release of IL-6 and IL-8 from SPOC1 or UNCN3T cells (P < 0.05).
SPOC1 and UNCN3T cell lines are better able to model the effect of mucus on drug absorption than the Calu-3 cell line and are proposed for use in assessing drug-mucus interactions in inhaled drug and formulation development.</description><subject>Airway epithelial cells</subject><subject>Animals</subject><subject>Cell Line</subject><subject>Cell-based assay</subject><subject>Cytokines - metabolism</subject><subject>Drug absorption</subject><subject>Epithelial Cells - cytology</subject><subject>Epithelial Cells - metabolism</subject><subject>Humans</subject><subject>Irritancy</subject><subject>Life Sciences & Biomedicine</subject><subject>Lung - cytology</subject><subject>Lung - metabolism</subject><subject>Mucin</subject><subject>Mucins - metabolism</subject><subject>Mucus - metabolism</subject><subject>Mucus barrier</subject><subject>Nasal drug delivery</subject><subject>Nasal Mucosa - cytology</subject><subject>Nasal Mucosa - metabolism</subject><subject>Permeability barrier</subject><subject>Pharmaceutical Preparations - administration & dosage</subject><subject>Pharmaceutical Preparations - metabolism</subject><subject>Pharmacology & Pharmacy</subject><subject>Pulmonary drug delivery</subject><subject>Rats</subject><subject>Respiratory Mucosa - cytology</subject><subject>Respiratory Mucosa - metabolism</subject><subject>Science & Technology</subject><subject>Testosterone</subject><subject>Testosterone - metabolism</subject><issn>0939-6411</issn><issn>1873-3441</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>HGBXW</sourceid><sourceid>EIF</sourceid><recordid>eNqNkdtq3DAQhkVpabZpX6AXRZctrV0dfYBSCCY9QEgKTa6FLI93tdjSItkJeYa-dGScLu1N6dWI0f_NMHwIvaYkp4QWH_c57A9tzgijOSnz1HqCNrQqecaFoE_RhtS8zgpB6Ql6EeOeECJKWT1HJ1xwzgjnG_TrDBs_HnSw0TvsezztAgAeZzPHLIIJMFm3xdqGO32PDQwDHqyDiN82epgz_gH__HHVUKxdh28um0t-_Q73PuA5AtYRt9YfdjqM2sA8WaMHPPoOhrhuAuz8kkvsMLvtS_Ss10OEV4_1FN18Ob9uvmUXV1-_N2cXmRFSTplseVe2nNB0pRAEDC8qyTSrZcsoBS6BElMWJei2qwrDauCipq3uZKqlkPwUfV7nHuZ2hM6Am4Ie1CHYUYd75bVVf_84u1Nbf6sqwRgtRBrA1gEm-BgD9EeWErWoUXu1qFGLGkVKlVoJevPn1iPy20UKVGvgDlrfR2PBGTjGkryiqmVdl2R5NnbSk_Wu8bObEvr-_9GU_rSmkwi4tRDUI9HZAGZSnbf_OuQBFCzA2w</recordid><startdate>202110</startdate><enddate>202110</enddate><creator>Lee, Diane F.</creator><creator>Lethem, Michael I.</creator><creator>Lansley, Alison B.</creator><general>Elsevier B.V</general><general>Elsevier</general><general>Elsevier Science</general><scope>6I.</scope><scope>AAFTH</scope><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</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>5PM</scope><orcidid>https://orcid.org/0000-0002-1521-3725</orcidid></search><sort><creationdate>202110</creationdate><title>A comparison of three mucus-secreting airway cell lines (Calu-3, SPOC1 and UNCN3T) for use as biopharmaceutical models of the nose and lung</title><author>Lee, Diane F. ; Lethem, Michael I. ; Lansley, Alison B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-5b3d7b301344440ec36852a295b211e35e10c767eabd86c29e3491bad53497453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Airway epithelial cells</topic><topic>Animals</topic><topic>Cell Line</topic><topic>Cell-based assay</topic><topic>Cytokines - metabolism</topic><topic>Drug absorption</topic><topic>Epithelial Cells - cytology</topic><topic>Epithelial Cells - metabolism</topic><topic>Humans</topic><topic>Irritancy</topic><topic>Life Sciences & Biomedicine</topic><topic>Lung - cytology</topic><topic>Lung - metabolism</topic><topic>Mucin</topic><topic>Mucins - metabolism</topic><topic>Mucus - metabolism</topic><topic>Mucus barrier</topic><topic>Nasal drug delivery</topic><topic>Nasal Mucosa - cytology</topic><topic>Nasal Mucosa - metabolism</topic><topic>Permeability barrier</topic><topic>Pharmaceutical Preparations - administration & dosage</topic><topic>Pharmaceutical Preparations - metabolism</topic><topic>Pharmacology & Pharmacy</topic><topic>Pulmonary drug delivery</topic><topic>Rats</topic><topic>Respiratory Mucosa - cytology</topic><topic>Respiratory Mucosa - metabolism</topic><topic>Science & Technology</topic><topic>Testosterone</topic><topic>Testosterone - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Diane F.</creatorcontrib><creatorcontrib>Lethem, Michael I.</creatorcontrib><creatorcontrib>Lansley, Alison B.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Web of Science - Science Citation Index Expanded - 2021</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>European journal of pharmaceutics and biopharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Diane F.</au><au>Lethem, Michael I.</au><au>Lansley, Alison B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A comparison of three mucus-secreting airway cell lines (Calu-3, SPOC1 and UNCN3T) for use as biopharmaceutical models of the nose and lung</atitle><jtitle>European journal of pharmaceutics and biopharmaceutics</jtitle><stitle>EUR J PHARM BIOPHARM</stitle><addtitle>Eur J Pharm Biopharm</addtitle><date>2021-10</date><risdate>2021</risdate><volume>167</volume><spage>159</spage><epage>174</epage><pages>159-174</pages><issn>0939-6411</issn><eissn>1873-3441</eissn><abstract>[Display omitted]
The aim of this work was to compare three existing mucus-secreting airway cell lines for use as models of the airways to study drug transport in the presence of mucus.
Each cell line secreted mature, glycosylated mucins, evidenced by the enzyme-linked lectin assay. The secretagogue, adenylyl-imidodiphosphate, increased mucin secretion in SPOC1 (3.5-fold) and UNCN3T (1.5-fold) cells but not in Calu-3 cells. In a novel mucus-depleted (MD) model the amount of mucus in the non-depleted wells was 3-, 8- and 4-fold higher than in the mucus-depleted wells of the Calu-3, SPOC1 and UNCN3T cells respectively. The permeability of 'high mucus’ cells to testosterone was significantly less in SPOC1 and UNCN3T cells (P < 0.05) but not Calu-3 cells.
Mucin secretion and cytokine release were investigated as indicators of drug irritancy in the SPOC1 and UNCN3T cell lines. A number of inhaled drugs significantly increased mucin secretion at high concentrations and the release of IL-6 and IL-8 from SPOC1 or UNCN3T cells (P < 0.05).
SPOC1 and UNCN3T cell lines are better able to model the effect of mucus on drug absorption than the Calu-3 cell line and are proposed for use in assessing drug-mucus interactions in inhaled drug and formulation development.</abstract><cop>AMSTERDAM</cop><pub>Elsevier B.V</pub><pmid>34332033</pmid><doi>10.1016/j.ejpb.2021.07.016</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-1521-3725</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | European journal of pharmaceutics and biopharmaceutics, 2021-10, Vol.167, p.159-174 |
| issn | 0939-6411 1873-3441 |
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| source | MEDLINE; Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" />; Access via ScienceDirect (Elsevier) |
| subjects | Airway epithelial cells Animals Cell Line Cell-based assay Cytokines - metabolism Drug absorption Epithelial Cells - cytology Epithelial Cells - metabolism Humans Irritancy Life Sciences & Biomedicine Lung - cytology Lung - metabolism Mucin Mucins - metabolism Mucus - metabolism Mucus barrier Nasal drug delivery Nasal Mucosa - cytology Nasal Mucosa - metabolism Permeability barrier Pharmaceutical Preparations - administration & dosage Pharmaceutical Preparations - metabolism Pharmacology & Pharmacy Pulmonary drug delivery Rats Respiratory Mucosa - cytology Respiratory Mucosa - metabolism Science & Technology Testosterone Testosterone - metabolism |
| title | A comparison of three mucus-secreting airway cell lines (Calu-3, SPOC1 and UNCN3T) for use as biopharmaceutical models of the nose and lung |
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