{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T01:59:00Z","timestamp":1778551140137,"version":"3.51.4"},"reference-count":36,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T00:00:00Z","timestamp":1704240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014729","name":"Philip Morris International","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014729","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmaceutical Sciences"],"published-print":{"date-parts":[[2024,3]]},"DOI":"10.1016\/j.ejps.2024.106693","type":"journal-article","created":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T06:18:34Z","timestamp":1704349114000},"page":"106693","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["Aerosol delivery and spatiotemporal tissue distribution of hydroxychloroquine in rat lung"],"prefix":"10.1016","volume":"194","author":[{"given":"Wenhao","family":"Xia","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4275-4260","authenticated-orcid":false,"given":"Aditya R","family":"Kolli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arkadiusz K","family":"Kuczaj","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justyna","family":"Szostak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon","family":"Lam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei Wen","family":"Toh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asef","family":"Purwanti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei Teck","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond","family":"Ng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blaine","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel C","family":"Peitsch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Hoeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejps.2024.106693_bib0001","unstructured":"AAALAC, 2011. Association for assessment and accreditation of laboratory animal care international. Guide for the care and use of laboratory animals: eighth edition. (accessed 09.17.23)."},{"key":"10.1016\/j.ejps.2024.106693_bib0002","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1080\/08958370802207318","article-title":"Association of Inhalation Toxicologists (AIT) working party recommendation for standard delivered dose calculation and expression in non-clinical aerosol inhalation toxicology studies with pharmaceuticals","volume":"20","author":"Alexander","year":"2008","journal-title":"Inhal. Toxicol."},{"key":"10.1016\/j.ejps.2024.106693_bib0003","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.ejps.2017.08.014","article-title":"Incorporation of lysosomal sequestration in the mechanistic model for prediction of tissue distribution of basic drugs","volume":"109","author":"Assmus","year":"2017","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.ejps.2024.106693_bib0004","doi-asserted-by":"crossref","first-page":"3432","DOI":"10.1016\/j.xphs.2016.08.014","article-title":"Lung retention by lysosomal trapping of inhaled drugs can be predicted in vitro with lung slices","volume":"105","author":"B\u00e4ckstr\u00f6m","year":"2016","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ejps.2024.106693_bib0005","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1080\/10717544.2018.1455762","article-title":"Uncovering the regional localization of inhaled salmeterol retention in the lung","volume":"25","author":"B\u00e4ckstr\u00f6m","year":"2018","journal-title":"Drug Deliv."},{"key":"10.1016\/j.ejps.2024.106693_bib0006","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1002\/jps.24575","article-title":"Development of a novel lung slice methodology for profiling of inhaled compounds","volume":"105","author":"B\u00e4ckstr\u00f6m","year":"2016","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ejps.2024.106693_bib0007","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1080\/02786828608959076","article-title":"Calibration and use of the aerodynamic particle sizer (APS 3300)","volume":"5","author":"Baron","year":"1986","journal-title":"Aerosol Sci. Technol."},{"key":"10.1016\/j.ejps.2024.106693_bib0008","article-title":"Recent advancements and application of in vitro models for predicting inhalation toxicity in humans","volume":"79","author":"Bedford","year":"2022","journal-title":"Toxicol. Vit."},{"key":"10.1016\/j.ejps.2024.106693_bib0009","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1124\/jpet.119.257311","article-title":"Translation of inhaled drug optimization strategies into clinical pharmacokinetics and pharmacodynamics using GSK2292767A, a novel inhaled phosphoinositide 3-kinase \u03b4 inhibitor","volume":"369","author":"Begg","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.ejps.2024.106693_bib0010","doi-asserted-by":"crossref","first-page":"3814","DOI":"10.1039\/C8LC01029C","article-title":"A lung\/liver-on-a-chip platform for acute and chronic toxicity studies","volume":"18","author":"Bovard","year":"2018","journal-title":"Lab Chip"},{"key":"10.1016\/j.ejps.2024.106693_bib0011","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1111\/jphp.12541","article-title":"The function and performance of aqueous aerosol devices for inhalation therapy","volume":"68","author":"Carvalho","year":"2016","journal-title":"J. Pharm. Pharmacol."},{"key":"10.1016\/j.ejps.2024.106693_bib0012","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.4155\/tde.13.71","article-title":"Liposomal formulations for inhalation","volume":"4","author":"Cipolla","year":"2013","journal-title":"Ther. Deliv."},{"key":"10.1016\/j.ejps.2024.106693_bib0013","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijantimicag.2020.106007","article-title":"Excessive lysosomal ion-trapping of hydroxychloroquine and azithromycin","volume":"55","author":"Derendorf","year":"2020","journal-title":"Int. J. Antimicrob. Agents."},{"key":"10.1016\/j.ejps.2024.106693_bib0014","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1513\/pats.200803-025HR","article-title":"Resident cellular components of the human lung: current knowledge and goals for research on cell phenotyping and function","volume":"5","author":"Franks","year":"2008","journal-title":"Proc. Am. Thorac. Soc."},{"key":"10.1016\/j.ejps.2024.106693_bib0015","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.addr.2020.07.006","article-title":"Emerging trends in inhaled drug delivery","volume":"157","author":"Hickey","year":"2020","journal-title":"Adv. Drug. Deliv. Rev."},{"key":"10.1016\/j.ejps.2024.106693_bib0016","doi-asserted-by":"crossref","DOI":"10.3390\/pharmaceutics12050408","article-title":"Towards a quantitative mechanistic understanding of localized pulmonary tissue retention - a combined in vivo\/in silico approach based on four model drugs","volume":"12","author":"Himstedt","year":"2020","journal-title":"Pharmaceutics"},{"key":"10.1016\/j.ejps.2024.106693_bib0017","unstructured":"Kassambara, A., 2020. ggpubr: \u201cggplot2\u201d based publication ready plots, R package version 0.4.0."},{"key":"10.1016\/j.ejps.2024.106693_bib0018","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s11095-021-03152-3","article-title":"Translational modeling of chloroquine and hydroxychloroquine dosimetry in human airways for treating viral respiratory infections","volume":"39","author":"Kolli","year":"2022","journal-title":"Pharm. Res."},{"key":"10.1016\/j.ejps.2024.106693_bib0019","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejps.2022.106321","article-title":"Deconvolution of systemic pharmacokinetics predicts inhaled aerosol dosimetry of nicotine","volume":"180","author":"Kolli","year":"2023","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.ejps.2024.106693_bib0020","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1080\/10408444.2019.1692780","article-title":"Bridging inhaled aerosol dosimetry to physiologically based pharmacokinetic modeling for toxicological assessment: nicotine delivery systems and beyond","volume":"49","author":"Kolli","year":"2019","journal-title":"Crit. Rev. Toxicol."},{"key":"10.1016\/j.ejps.2024.106693_bib0021","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1208\/s12248-021-00666-x","article-title":"Pulmonary delivery of aerosolized chloroquine and hydroxychloroquine to treat COVID-19: in vitro experimentation to human dosing predictions","volume":"24","author":"Kolli","year":"2022","journal-title":"AAPS J."},{"key":"10.1016\/j.ejps.2024.106693_bib0022","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1046\/j.1365-2125.2003.01892.x","article-title":"Pulmonary drug delivery. Part I: physiological factors affecting therapeutic effectiveness of aerosolized medications","volume":"56","author":"Labiris","year":"2003","journal-title":"Br. J. Clin. Pharmacol."},{"key":"10.1016\/j.ejps.2024.106693_bib0023","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1046\/j.1365-2125.2003.01893.x","article-title":"Pulmonary drug delivery. Part II: the role of inhalant delivery devices and drug formulations in therapeutic effectiveness of aerosolized medications","volume":"56","author":"Labiris","year":"2003","journal-title":"Br. J. Clin. Pharmacol."},{"key":"10.1016\/j.ejps.2024.106693_bib0024","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1080\/02786829108959504","article-title":"A microorifice uniform deposit impactor (MOUDI): description, calibration, and use","volume":"14","author":"Marple","year":"1991","journal-title":"Aerosol Sci. Technol."},{"key":"10.1016\/j.ejps.2024.106693_bib0025","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0021-8502(73)90006-2","article-title":"The collison nebulizer: description, performance and application","volume":"4","author":"May","year":"1973","journal-title":"J. Aerosol Sci."},{"key":"10.1016\/j.ejps.2024.106693_bib0026","series-title":"Guidelines on the Care and Use of Animals for Scientific Purposes","year":"2022"},{"key":"10.1016\/j.ejps.2024.106693_bib0027","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.drudis.2021.09.005","article-title":"Developing inhaled drugs for respiratory diseases: a medicinal chemistry perspective","volume":"27","author":"Pasqua","year":"2022","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.ejps.2024.106693_bib0028","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1513\/pats.200409-049TA","article-title":"The lungs as a portal of entry for systemic drug delivery","volume":"1","author":"Patton","year":"2004","journal-title":"Proc. Am. Thorac. Soc."},{"key":"10.1016\/j.ejps.2024.106693_bib0029","unstructured":"RCoreTeam, 2022. R: a language and environment for statistical computing. R foundation for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https:\/\/www.R-project.org\/."},{"key":"10.1016\/j.ejps.2024.106693_bib0030","first-page":"1","article-title":"Deposition of 11C-radiolabeled nicotine-containing aerosol in an airway cast model using positron emission tomography (PET)","author":"Rose","year":"2023","journal-title":"Aerosol Sci. Technol."},{"key":"10.1016\/j.ejps.2024.106693_bib0031","doi-asserted-by":"crossref","first-page":"4440","DOI":"10.1111\/bph.15621","article-title":"Lung pharmacokinetics of inhaled and systemic drugs: a clinical evaluation","volume":"178","author":"Sadiq","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejps.2024.106693_bib0032","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1080\/08958370290084647","article-title":"Physiologically based pharmacokinetic modeling of styrene and styrene oxide respiratory-tract dosimetry in rodents and humans","volume":"14","author":"Sarangapani","year":"2002","journal-title":"Inhal. Toxicol."},{"key":"10.1016\/j.ejps.2024.106693_bib0033","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2023.1114739","article-title":"A multiplex inhalation platform to model in situ like aerosol delivery in a breathing lung-on-chip","volume":"14","author":"Sengupta","year":"2023","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.ejps.2024.106693_bib0034","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/cts.12923","article-title":"A strategy to treat COVID-19 disease with targeted delivery of inhalable liposomal hydroxychloroquine: a preclinical pharmacokinetic study","volume":"14","author":"Tai","year":"2021","journal-title":"Clin. Transl. Sci."},{"key":"10.1016\/j.ejps.2024.106693_bib0035","doi-asserted-by":"crossref","DOI":"10.3390\/pharmaceutics13081260","article-title":"Nebulised isotonic hydroxychloroquine aerosols for potential treatment of COVID-19","volume":"13","author":"Tai","year":"2021","journal-title":"Pharmaceutics"},{"key":"10.1016\/j.ejps.2024.106693_bib0036","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1177\/1091581815624080","article-title":"Symposium summary:\u201cBreathe in, breathe out, its easy: what you need to know about developing inhaled drugs","volume":"35","author":"Tepper","year":"2016","journal-title":"Int. J. Toxicol."}],"container-title":["European Journal of Pharmaceutical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0928098724000046?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0928098724000046?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T12:08:02Z","timestamp":1760530082000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0928098724000046"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3]]},"references-count":36,"alternative-id":["S0928098724000046"],"URL":"https:\/\/doi.org\/10.1016\/j.ejps.2024.106693","relation":{},"ISSN":["0928-0987"],"issn-type":[{"value":"0928-0987","type":"print"}],"subject":[],"published":{"date-parts":[[2024,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Aerosol delivery and spatiotemporal tissue distribution of hydroxychloroquine in rat lung","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmaceutical Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejps.2024.106693","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"106693"}}