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dc.contributor.authorBodhaniya, Aateka
dc.contributor.authorHoffman, Ewelina
dc.contributor.authorBall, Dough
dc.contributor.authorKlapwijk, Jan
dc.contributor.authorSteven, Rory T.
dc.contributor.authorDexter, Alex
dc.contributor.authorBunch, Josephine
dc.contributor.authorBaker, Daniel
dc.contributor.authorMurnane, Darragh
dc.contributor.authorHutter, Victoria
dc.contributor.authorPage, Clive
dc.contributor.authorDailey, Lea Ann
dc.contributor.authorForbes, Ben
dc.date.accessioned2019-09-13T00:08:05Z
dc.date.available2019-09-13T00:08:05Z
dc.date.issued2019-07-17
dc.identifier.citationBodhaniya , A , Hoffman , E , Ball , D , Klapwijk , J , Steven , R T , Dexter , A , Bunch , J , Baker , D , Murnane , D , Hutter , V , Page , C , Dailey , L A & Forbes , B 2019 , ' Comparison of Oral, Intranasal and Aerosol Administration of Amiodarone in Rats as a Model of Pulmonary Phospholipidosis. ' , Pharmaceutics , vol. 11 , no. 7 , 345 . https://doi.org/10.3390/pharmaceutics11070345
dc.identifier.issn1999-4923
dc.identifier.otherPURE: 17364800
dc.identifier.otherPURE UUID: 23e36929-08e4-460e-aafc-83ec2cd6db29
dc.identifier.otherScopus: 85071395493
dc.identifier.otherPubMed: 31319538
dc.identifier.otherORCID: /0000-0002-7998-924X/work/62750776
dc.identifier.otherORCID: /0000-0002-4172-0827/work/68244649
dc.identifier.urihttp://hdl.handle.net/2299/21674
dc.description.abstract‘Foamy’ alveolar macrophages (FAM) observed in nonclinical toxicology studies during inhaled drug development may indicate drug-induced phospholipidosis, but can also derive from adaptive non-adverse mechanisms. Orally administered amiodarone is currently used as a model of pulmonary phospholipidosis and it was hypothesized that aerosol administration would produce phospholipidosis-induced FAM that could be characterized and used in comparative inhalation toxicology. Han-Wistar rats were given amiodarone via (1) intranasal administration (6.25 mg/kg) on two days, (2) aerosol administration (3 mg/kg) on two days, (3) aerosol administration (10 mg/kg) followed by three days of 30 mg/kg or (4) oral administration (100 mg/kg) for 7 days. Alveolar macrophages in bronchoalveolar lavage were evaluated by di_erential cell counting and high content fluorescence imaging. Histopathology and mass-spectrometry imaging (MSI) were performed on lung slices. The higher dose aerosolised amiodarone caused transient pulmonary inflammation (p < 0.05), but only oral amiodarone resulted in FAM (p < 0.001). MSI of the lungs of orally treated rats revealed a homogenous distribution of amiodarone and a putative phospholipidosis marker, di-22:6 bis-monoacylglycerol, throughout lung tissue whereas aerosol administration resulted in localization of both compounds around the airway lumen. Thus, unlike oral administration, aerosolised amiodarone failed to produce the expected FAM responses.en
dc.language.isoeng
dc.relation.ispartofPharmaceutics
dc.subjectphospholipidosis
dc.subjectfoamy alveolar macrophage
dc.subjecthigh content analysis
dc.subjectFoamy alveolar macrophages
dc.subjectDi-22:6 bis-monoacylglycerol
dc.subjectMass spectrometry imaging
dc.subjectAmiodarone
dc.subjectHigh content analysis
dc.subjectPhospholipidosis
dc.subjectPharmaceutical Science
dc.titleComparison of Oral, Intranasal and Aerosol Administration of Amiodarone in Rats as a Model of Pulmonary Phospholipidosis.en
dc.contributor.institutionDepartment of Clinical and Pharmaceutical Sciences
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionCentre for Research into Topical Drug Delivery and Toxicology
dc.description.statusPeer reviewed
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85071395493&partnerID=8YFLogxK
rioxxterms.versionVoR
rioxxterms.versionofrecordhttps://doi.org/10.3390/pharmaceutics11070345
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


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