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Inhaled aerosol dose distribution between proximal bronchi and lung periphery

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Eur J Pharm Biopharm_Verbanck_Usmani_28nov2019_R1.docxAccepted version62.38 kBMicrosoft WordView/Open
Verbanck_Usmani_28nov2019_OnlineRepos_R1.docxSupporting information398.68 kBMicrosoft WordView/Open
Title: Inhaled aerosol dose distribution between proximal bronchi and lung periphery
Authors: Verbanck, S
Biddiscombe, MF
Usmani, OS
Item Type: Journal Article
Abstract: Modern inhaled drug discovery programs assess dose delivery to proximal and distal airways using rudimentary imaging indices, where relative deposition is estimated by generically defined 'central' and 'peripheral' lung regions. Utilizing recent data linking the proximal airway topology to a characteristic pattern of aerosol lung deposition, we provide a direct measure of dose distribution between the proximal bronchi and the distal lung. We analyzed scintigraphic lung images of twelve asthma patients following inhalation of 1.5-, 3- and 6-µm monodisperse drug particles at breathing flows of 30- and 60-L/min. We explicitly used the central hot-spots associated with each patient's specific bronchial topology to obtain a direct measure of aerosol deposition in the proximal bronchi, rather than applying standard templates of lung boundaries. Maximum deposition in the central bronchi (as % of lung deposition) was 52±10(SD)% (6µm;60L/min). Minimum central deposition was 17±2(SD)% (1.5µm;30L/min) where the 83% aerosol 'escaping' deposition in the central bronchi reached 75±17(SD)% of the lung area that could be reached by Krypton gas. For all particle sizes, hot-spots appeared in the same patient-specific central airway location, with greatest intensity at 60L/min. For a range of respirable aerosol sizes and breathing flows, we have quantified deposited dose in the proximal bronchi and their distal lung reach, constituting a platform to support therapeutic inhaled aerosol drug development.
Issue Date: 1-Jul-2020
Date of Acceptance: 28-Apr-2020
URI: http://hdl.handle.net/10044/1/79859
DOI: 10.1016/j.ejpb.2020.04.019
ISSN: 0939-6411
Publisher: Elsevier
Start Page: 18
End Page: 22
Journal / Book Title: European Journal of Pharmaceutics and Biopharmaceutics
Volume: 152
Copyright Statement: © 2020 Elsevier B.V. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Aerosol drug dose
Central airways
Drug targeting
Hot-spots
In situ lung imaging
Inhalation therapy
Aerosol drug dose
Central airways
Drug targeting
Hot-spots
In situ lung imaging
Inhalation therapy
Pharmacology & Pharmacy
1115 Pharmacology and Pharmaceutical Sciences
Publication Status: Published
Conference Place: Netherlands
Online Publication Date: 2020-05-01
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine