In Silico<i> </i>Optimization of Fiber-Shaped Aerosols in Inhalation Therapy for Augmented Targeting and Deposition across the Respiratory Tract

Motivated by a desire to uncover new opportunities for designing the size and shape of fiber-shaped aerosols towards improved pulmonary drug delivery deposition outcomes, we explore the transport and deposition characteristics of fibers under physiologically inspired inhalation conditions in silico,...

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Main Authors:	Lihi Shachar-Berman, Saurabh Bhardwaj, Yan Ostrovski, Prashant Das, Pantelis Koullapis, Stavros Kassinos, Josué Sznitman
Format:	Article
Language:	English
Published:	MDPI AG 2020-03-01
Series:	Pharmaceutics
Subjects:	in silico simulations computational fluid dynamics inhalation therapy aerosols fibers respiratory tract
Online Access:	https://www.mdpi.com/1999-4923/12/3/230

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spelling	doaj-f605c0716d08495fa2217e627282c0e22020-11-25T02:57:37ZengMDPI AGPharmaceutics1999-49232020-03-0112323010.3390/pharmaceutics12030230pharmaceutics12030230In Silico<i> </i>Optimization of Fiber-Shaped Aerosols in Inhalation Therapy for Augmented Targeting and Deposition across the Respiratory TractLihi Shachar-Berman0Saurabh Bhardwaj1Yan Ostrovski2Prashant Das3Pantelis Koullapis4Stavros Kassinos5Josué Sznitman6Department of Biomedical Engineering, Technion—Israel Institute of Technology, Haifa 3200003, IsraelDepartment of Biomedical Engineering, Technion—Israel Institute of Technology, Haifa 3200003, IsraelDepartment of Biomedical Engineering, Technion—Israel Institute of Technology, Haifa 3200003, IsraelDepartment of Mechanical Engineering, University of Alberta, Edmonton, AB T6G 2R3, CanadaComputational Sciences Laboratory (UCY-CompSci), Department of Mechanical and Manufacturing Engineering, University of Cyprus, Nicosia 1678, CyprusComputational Sciences Laboratory (UCY-CompSci), Department of Mechanical and Manufacturing Engineering, University of Cyprus, Nicosia 1678, CyprusDepartment of Biomedical Engineering, Technion—Israel Institute of Technology, Haifa 3200003, IsraelMotivated by a desire to uncover new opportunities for designing the size and shape of fiber-shaped aerosols towards improved pulmonary drug delivery deposition outcomes, we explore the transport and deposition characteristics of fibers under physiologically inspired inhalation conditions in silico,<i> </i>mimicking a dry powder inhaler (DPI) maneuver in adult lung models. Here, using computational fluid dynamics (CFD) simulations, we resolve the transient translational and rotational motion of inhaled micron-sized ellipsoid particles under the influence of aerodynamic (i.e., drag, lift) and gravitational forces in a respiratory tract model spanning the first seven bifurcating generations (i.e., from the mouth to upper airways), coupled to a more distal airway model representing nine generations of the mid-bronchial tree. Aerosol deposition efficiencies are quantified as a function of the equivalent diameter (<i>d</i><sub>p</sub>) and geometrical aspect ratio (<i>AR</i>), and these are compared to outcomes with traditional spherical particles of equivalent mass. Our results help elucidate how deposition patterns are intimately coupled to <i>d</i><sub>p</sub> and <i>AR</i>, whereby high <i>AR</i> fibers in the narrow range of <i>d</i><sub>p</sub> = 6−7 µm yield the highest deposition efficiency for targeting the upper- and mid-bronchi, whereas fibers in the range of <i>d</i><sub>p</sub>= 4−6 µm are anticipated to cross through the conducting regions and reach the deeper lung regions. Our efforts underscore previously uncovered opportunities to design the shape and size of fiber-like aerosols towards targeted pulmonary drug delivery with increased deposition efficiencies, in particular by leveraging their large payloads for deep lung deposition.https://www.mdpi.com/1999-4923/12/3/230in silico simulationscomputational fluid dynamicsinhalation therapyaerosolsfibersrespiratory tract
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Lihi Shachar-Berman Saurabh Bhardwaj Yan Ostrovski Prashant Das Pantelis Koullapis Stavros Kassinos Josué Sznitman
spellingShingle	Lihi Shachar-Berman Saurabh Bhardwaj Yan Ostrovski Prashant Das Pantelis Koullapis Stavros Kassinos Josué Sznitman In Silico<i> </i>Optimization of Fiber-Shaped Aerosols in Inhalation Therapy for Augmented Targeting and Deposition across the Respiratory Tract Pharmaceutics in silico simulations computational fluid dynamics inhalation therapy aerosols fibers respiratory tract
author_facet	Lihi Shachar-Berman Saurabh Bhardwaj Yan Ostrovski Prashant Das Pantelis Koullapis Stavros Kassinos Josué Sznitman
author_sort	Lihi Shachar-Berman
title	In Silico<i> </i>Optimization of Fiber-Shaped Aerosols in Inhalation Therapy for Augmented Targeting and Deposition across the Respiratory Tract
title_short	In Silico<i> </i>Optimization of Fiber-Shaped Aerosols in Inhalation Therapy for Augmented Targeting and Deposition across the Respiratory Tract
title_full	In Silico<i> </i>Optimization of Fiber-Shaped Aerosols in Inhalation Therapy for Augmented Targeting and Deposition across the Respiratory Tract
title_fullStr	In Silico<i> </i>Optimization of Fiber-Shaped Aerosols in Inhalation Therapy for Augmented Targeting and Deposition across the Respiratory Tract
title_full_unstemmed	In Silico<i> </i>Optimization of Fiber-Shaped Aerosols in Inhalation Therapy for Augmented Targeting and Deposition across the Respiratory Tract
title_sort	in silico<i> </i>optimization of fiber-shaped aerosols in inhalation therapy for augmented targeting and deposition across the respiratory tract
publisher	MDPI AG
series	Pharmaceutics
issn	1999-4923
publishDate	2020-03-01
description	Motivated by a desire to uncover new opportunities for designing the size and shape of fiber-shaped aerosols towards improved pulmonary drug delivery deposition outcomes, we explore the transport and deposition characteristics of fibers under physiologically inspired inhalation conditions in silico,<i> </i>mimicking a dry powder inhaler (DPI) maneuver in adult lung models. Here, using computational fluid dynamics (CFD) simulations, we resolve the transient translational and rotational motion of inhaled micron-sized ellipsoid particles under the influence of aerodynamic (i.e., drag, lift) and gravitational forces in a respiratory tract model spanning the first seven bifurcating generations (i.e., from the mouth to upper airways), coupled to a more distal airway model representing nine generations of the mid-bronchial tree. Aerosol deposition efficiencies are quantified as a function of the equivalent diameter (<i>d</i><sub>p</sub>) and geometrical aspect ratio (<i>AR</i>), and these are compared to outcomes with traditional spherical particles of equivalent mass. Our results help elucidate how deposition patterns are intimately coupled to <i>d</i><sub>p</sub> and <i>AR</i>, whereby high <i>AR</i> fibers in the narrow range of <i>d</i><sub>p</sub> = 6−7 µm yield the highest deposition efficiency for targeting the upper- and mid-bronchi, whereas fibers in the range of <i>d</i><sub>p</sub>= 4−6 µm are anticipated to cross through the conducting regions and reach the deeper lung regions. Our efforts underscore previously uncovered opportunities to design the shape and size of fiber-like aerosols towards targeted pulmonary drug delivery with increased deposition efficiencies, in particular by leveraging their large payloads for deep lung deposition.
topic	in silico simulations computational fluid dynamics inhalation therapy aerosols fibers respiratory tract
url	https://www.mdpi.com/1999-4923/12/3/230
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In Silico<i> </i>Optimization of Fiber-Shaped Aerosols in Inhalation Therapy for Augmented Targeting and Deposition across the Respiratory Tract

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