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Comparison of Oral, Intranasal and Aerosol Administration of Amiodarone in Rats as a Model of Pulmonary Phospholipidosis. / Bodhaniya, Aateka; Hoffman, Ewelina; Ball, Dough; Klapwijk, Jan; Steven, Rory T. ; Dexter, Alex; Bunch, Josephine ; Baker, Daniel; Murnane, Darragh; Hutter, Victoria; Page, Clive; Dailey, Lea Ann; Forbes, Ben.

In: Pharmaceutics, Vol. 11, No. 7, 345, 17.07.2019.

Research output: Contribution to journalArticlepeer-review

Harvard

Bodhaniya, A, Hoffman, E, Ball, D, Klapwijk, J, Steven, RT, Dexter, A, Bunch, J, Baker, D, Murnane, D, Hutter, V, Page, C, Dailey, LA & 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

APA

Bodhaniya, 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, 11(7), [345]. https://doi.org/10.3390/pharmaceutics11070345

Vancouver

Author

Bodhaniya, Aateka ; Hoffman, Ewelina ; Ball, Dough ; Klapwijk, Jan ; Steven, Rory T. ; Dexter, Alex ; Bunch, Josephine ; Baker, Daniel ; Murnane, Darragh ; Hutter, Victoria ; Page, Clive ; Dailey, Lea Ann ; Forbes, Ben. / Comparison of Oral, Intranasal and Aerosol Administration of Amiodarone in Rats as a Model of Pulmonary Phospholipidosis. In: Pharmaceutics. 2019 ; Vol. 11, No. 7.

Bibtex

@article{23e3692908e4460eaafc83ec2cd6db29,
title = "Comparison of Oral, Intranasal and Aerosol Administration of Amiodarone in Rats as a Model of Pulmonary Phospholipidosis.",
abstract = "{\textquoteleft}Foamy{\textquoteright} 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.",
keywords = "phospholipidosis, foamy alveolar macrophage, high content analysis, Foamy alveolar macrophages, Di-22:6 bis-monoacylglycerol, Mass spectrometry imaging, Amiodarone, High content analysis, Phospholipidosis",
author = "Aateka Bodhaniya and Ewelina Hoffman and Dough Ball and Jan Klapwijk and Steven, {Rory T.} and Alex Dexter and Josephine Bunch and Daniel Baker and Darragh Murnane and Victoria Hutter and Clive Page and Dailey, {Lea Ann} and Ben Forbes",
year = "2019",
month = jul,
day = "17",
doi = "10.3390/pharmaceutics11070345",
language = "English",
volume = "11",
journal = "Pharmaceutics",
issn = "1999-4923",
publisher = "MDPI",
number = "7",

}

RIS

TY - JOUR

T1 - Comparison of Oral, Intranasal and Aerosol Administration of Amiodarone in Rats as a Model of Pulmonary Phospholipidosis.

AU - Bodhaniya, Aateka

AU - Hoffman, Ewelina

AU - Ball, Dough

AU - Klapwijk, Jan

AU - Steven, Rory T.

AU - Dexter, Alex

AU - Bunch, Josephine

AU - Baker, Daniel

AU - Murnane, Darragh

AU - Hutter, Victoria

AU - Page, Clive

AU - Dailey, Lea Ann

AU - Forbes, Ben

PY - 2019/7/17

Y1 - 2019/7/17

N2 - ‘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.

AB - ‘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.

KW - phospholipidosis

KW - foamy alveolar macrophage

KW - high content analysis

KW - Foamy alveolar macrophages

KW - Di-22:6 bis-monoacylglycerol

KW - Mass spectrometry imaging

KW - Amiodarone

KW - High content analysis

KW - Phospholipidosis

UR - http://www.scopus.com/inward/record.url?scp=85071395493&partnerID=8YFLogxK

U2 - 10.3390/pharmaceutics11070345

DO - 10.3390/pharmaceutics11070345

M3 - Article

C2 - 31319538

VL - 11

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 7

M1 - 345

ER -