Assessment of in vitro kinetics and biological impact of nebulized trehalose on human bronchial epithelium
Trehalose is added in drug formulations to act as fillers or improve aerosolization performance. Its characteristics as a carrier molecule have been explored; however, the fate of trehalose in human airway tissues has not been thoroughly investigated. Here, we investigated the fate of nebulized treh...
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| Veröffentlicht in: | Food and chemical toxicology 2021-11, Vol.157, p.112577-112577, Article 112577 |
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| creator | Iskandar, Anita R. Kolli, Aditya Reddy Giralt, Albert Neau, Laurent Fatarova, Maria Kondylis, Athanasios Torres, Laura Ortega Majeed, Shoaib Merg, Celine Corciulo, Maica Trivedi, Keyur Guedj, Emmanuel Frentzel, Stefan Calvino, Florian Guy, Philippe Alexandre Ivanov, Nikolai V. Peitsch, Manuel C. Hoeng, Julia |
| description | Trehalose is added in drug formulations to act as fillers or improve aerosolization performance. Its characteristics as a carrier molecule have been explored; however, the fate of trehalose in human airway tissues has not been thoroughly investigated. Here, we investigated the fate of nebulized trehalose using in vitro human air-liquid bronchial epithelial cultures. First, a tracing experiment was conducted using 13C12-trehalose; we measured trehalose distribution in different culture compartments (apical surface liquid, epithelial culture, and basal side medium) at various time points following acute exposure to 13C12-labeled trehalose. We found that 13C12-trehalose was metabolized into 13C6-glucose. The data was then used to model the kinetics of trehalose disappearance from the apical surface of bronchial cultures. Secondly, we evaluated the potential adverse effects of nebulized trehalose on the bronchial cultures after they were acutely exposed to nebulized trehalose up to a level just below its solubility limit (50 g/100 g water). We assessed the ciliary beating frequency and histological characteristics. We found that nebulized trehalose did not lead to marked alteration in ciliary beating frequency and morphology of the epithelial cultures. The in vitro testing approach used here may enable the early selection of excipients for future development of inhalation products.
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| doi_str_mv | 10.1016/j.fct.2021.112577 |
| format | Article |
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[Display omitted]</description><identifier>ISSN: 0278-6915</identifier><identifier>EISSN: 1873-6351</identifier><identifier>DOI: 10.1016/j.fct.2021.112577</identifier><identifier>PMID: 34563633</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Aerosols - administration & dosage ; Aerosols - pharmacokinetics ; Aerosols - pharmacology ; Airway epithelial cultures ; Bronchi - drug effects ; Bronchi - metabolism ; Cells, Cultured ; Excipients ; Humans ; Inhalation ; Kinetics ; Nebulizers and Vaporizers ; Organotypic cultures ; Respiratory Mucosa - drug effects ; Respiratory Mucosa - metabolism ; Trehalose ; Trehalose - administration & dosage ; Trehalose - pharmacokinetics ; Trehalose - pharmacology</subject><ispartof>Food and chemical toxicology, 2021-11, Vol.157, p.112577-112577, Article 112577</ispartof><rights>2021 The Authors</rights><rights>Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-cc7a54a6a7e634475d813775979f3391611bb5aa12c29cb1d04fcaf4cdd9879d3</citedby><cites>FETCH-LOGICAL-c396t-cc7a54a6a7e634475d813775979f3391611bb5aa12c29cb1d04fcaf4cdd9879d3</cites><orcidid>0000-0002-4275-4260 ; 0000-0001-5324-359X ; 0000-0001-9270-124X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.fct.2021.112577$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,778,782,3539,27911,27912,45982</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34563633$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Iskandar, Anita R.</creatorcontrib><creatorcontrib>Kolli, Aditya Reddy</creatorcontrib><creatorcontrib>Giralt, Albert</creatorcontrib><creatorcontrib>Neau, Laurent</creatorcontrib><creatorcontrib>Fatarova, Maria</creatorcontrib><creatorcontrib>Kondylis, Athanasios</creatorcontrib><creatorcontrib>Torres, Laura Ortega</creatorcontrib><creatorcontrib>Majeed, Shoaib</creatorcontrib><creatorcontrib>Merg, Celine</creatorcontrib><creatorcontrib>Corciulo, Maica</creatorcontrib><creatorcontrib>Trivedi, Keyur</creatorcontrib><creatorcontrib>Guedj, Emmanuel</creatorcontrib><creatorcontrib>Frentzel, Stefan</creatorcontrib><creatorcontrib>Calvino, Florian</creatorcontrib><creatorcontrib>Guy, Philippe Alexandre</creatorcontrib><creatorcontrib>Ivanov, Nikolai V.</creatorcontrib><creatorcontrib>Peitsch, Manuel C.</creatorcontrib><creatorcontrib>Hoeng, Julia</creatorcontrib><title>Assessment of in vitro kinetics and biological impact of nebulized trehalose on human bronchial epithelium</title><title>Food and chemical toxicology</title><addtitle>Food Chem Toxicol</addtitle><description>Trehalose is added in drug formulations to act as fillers or improve aerosolization performance. Its characteristics as a carrier molecule have been explored; however, the fate of trehalose in human airway tissues has not been thoroughly investigated. Here, we investigated the fate of nebulized trehalose using in vitro human air-liquid bronchial epithelial cultures. First, a tracing experiment was conducted using 13C12-trehalose; we measured trehalose distribution in different culture compartments (apical surface liquid, epithelial culture, and basal side medium) at various time points following acute exposure to 13C12-labeled trehalose. We found that 13C12-trehalose was metabolized into 13C6-glucose. The data was then used to model the kinetics of trehalose disappearance from the apical surface of bronchial cultures. Secondly, we evaluated the potential adverse effects of nebulized trehalose on the bronchial cultures after they were acutely exposed to nebulized trehalose up to a level just below its solubility limit (50 g/100 g water). We assessed the ciliary beating frequency and histological characteristics. We found that nebulized trehalose did not lead to marked alteration in ciliary beating frequency and morphology of the epithelial cultures. The in vitro testing approach used here may enable the early selection of excipients for future development of inhalation products.
[Display omitted]</description><subject>Aerosols - administration & dosage</subject><subject>Aerosols - pharmacokinetics</subject><subject>Aerosols - pharmacology</subject><subject>Airway epithelial cultures</subject><subject>Bronchi - drug effects</subject><subject>Bronchi - metabolism</subject><subject>Cells, Cultured</subject><subject>Excipients</subject><subject>Humans</subject><subject>Inhalation</subject><subject>Kinetics</subject><subject>Nebulizers and Vaporizers</subject><subject>Organotypic cultures</subject><subject>Respiratory Mucosa - drug effects</subject><subject>Respiratory Mucosa - metabolism</subject><subject>Trehalose</subject><subject>Trehalose - administration & dosage</subject><subject>Trehalose - pharmacokinetics</subject><subject>Trehalose - pharmacology</subject><issn>0278-6915</issn><issn>1873-6351</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEFv1DAQRi1URJfCD-gF-dhLFk-c2Ik4VVWBSpW4wNly7El3lsTe2kkl-PV12ZZjT3N535PmMXYOYgsC1Of9dnTLthY1bAHqVus3bAOdlpWSLZywjah1V6ke2lP2Pue9EEKDVu_YqWxaJZWUG7a_zBlznjEsPI6cAn-gJUX-mwIu5DK3wfOB4hTvyNmJ03yw7h8acFgn-oueLwl3dooZeQx8t8428CHF4HZUBnigZYcTrfMH9na0U8aPz_eM_fp6_fPqe3X749vN1eVt5WSvlso5bdvGKqtRyabRre9Aat32uh-l7EEBDENrLdSu7t0AXjSjs2PjvO873Xt5xi6O3kOK9yvmxcyUHU6TDRjXbEqo0kSKuisoHFGXYs4JR3NINNv0x4AwT4nN3pTE5imxOSYum0_P-nWY0f9fvDQtwJcjgOXJB8JksiMMDj0lLDIf6RX9I515jX4</recordid><startdate>202111</startdate><enddate>202111</enddate><creator>Iskandar, Anita R.</creator><creator>Kolli, Aditya Reddy</creator><creator>Giralt, Albert</creator><creator>Neau, Laurent</creator><creator>Fatarova, Maria</creator><creator>Kondylis, Athanasios</creator><creator>Torres, Laura Ortega</creator><creator>Majeed, Shoaib</creator><creator>Merg, Celine</creator><creator>Corciulo, Maica</creator><creator>Trivedi, Keyur</creator><creator>Guedj, Emmanuel</creator><creator>Frentzel, Stefan</creator><creator>Calvino, Florian</creator><creator>Guy, Philippe Alexandre</creator><creator>Ivanov, Nikolai V.</creator><creator>Peitsch, Manuel C.</creator><creator>Hoeng, Julia</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope><orcidid>https://orcid.org/0000-0002-4275-4260</orcidid><orcidid>https://orcid.org/0000-0001-5324-359X</orcidid><orcidid>https://orcid.org/0000-0001-9270-124X</orcidid></search><sort><creationdate>202111</creationdate><title>Assessment of in vitro kinetics and biological impact of nebulized trehalose on human bronchial epithelium</title><author>Iskandar, Anita R. ; 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Its characteristics as a carrier molecule have been explored; however, the fate of trehalose in human airway tissues has not been thoroughly investigated. Here, we investigated the fate of nebulized trehalose using in vitro human air-liquid bronchial epithelial cultures. First, a tracing experiment was conducted using 13C12-trehalose; we measured trehalose distribution in different culture compartments (apical surface liquid, epithelial culture, and basal side medium) at various time points following acute exposure to 13C12-labeled trehalose. We found that 13C12-trehalose was metabolized into 13C6-glucose. The data was then used to model the kinetics of trehalose disappearance from the apical surface of bronchial cultures. Secondly, we evaluated the potential adverse effects of nebulized trehalose on the bronchial cultures after they were acutely exposed to nebulized trehalose up to a level just below its solubility limit (50 g/100 g water). We assessed the ciliary beating frequency and histological characteristics. We found that nebulized trehalose did not lead to marked alteration in ciliary beating frequency and morphology of the epithelial cultures. The in vitro testing approach used here may enable the early selection of excipients for future development of inhalation products.
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| identifier | ISSN: 0278-6915 |
| ispartof | Food and chemical toxicology, 2021-11, Vol.157, p.112577-112577, Article 112577 |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Aerosols - administration & dosage Aerosols - pharmacokinetics Aerosols - pharmacology Airway epithelial cultures Bronchi - drug effects Bronchi - metabolism Cells, Cultured Excipients Humans Inhalation Kinetics Nebulizers and Vaporizers Organotypic cultures Respiratory Mucosa - drug effects Respiratory Mucosa - metabolism Trehalose Trehalose - administration & dosage Trehalose - pharmacokinetics Trehalose - pharmacology |
| title | Assessment of in vitro kinetics and biological impact of nebulized trehalose on human bronchial epithelium |
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