Pulsatile Bi-Directional Aerosol Flow Affects Aerosol Delivery to the Intranasal Olfactory Region: A Patient-Specific Computational Study

The nasal olfactory region is a potential route for non-invasive delivery of drugs directly from the nasal epithelium to the brain, bypassing the often impermeable blood-brain barrier. However, efficient aerosol delivery to the olfactory region is challenging due to its location in the nose. Here we...

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Autores principales:	Ali Farnoud, Hesam Tofighian, Ingo Baumann, Andrew R. Martin, Mohammad M. Rashidi, Micheal P. Menden, Otmar Schmid
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	nose to brain drug delivery olfactory region bi-directional aerosol delivery pulsatile drug delivery computational fluid dynamics large eddy simulations Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/784ad23d6aaa41f3aeffb11bd26bc5d2
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spelling	oai:doaj.org-article:784ad23d6aaa41f3aeffb11bd26bc5d22021-11-30T12:29:57ZPulsatile Bi-Directional Aerosol Flow Affects Aerosol Delivery to the Intranasal Olfactory Region: A Patient-Specific Computational Study1663-981210.3389/fphar.2021.746420https://doaj.org/article/784ad23d6aaa41f3aeffb11bd26bc5d22021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.746420/fullhttps://doaj.org/toc/1663-9812The nasal olfactory region is a potential route for non-invasive delivery of drugs directly from the nasal epithelium to the brain, bypassing the often impermeable blood-brain barrier. However, efficient aerosol delivery to the olfactory region is challenging due to its location in the nose. Here we explore aerosol delivery with bi-directional pulsatile flow conditions for targeted drug delivery to the olfactory region using a computational fluid dynamics (CFD) model on the patient-specific nasal geometry. Aerosols with aerodynamic diameter of 1 µm, which is large enough for delivery of large enough drug doses and yet potentially small enough for non-inertial aerosol deposition due to, e.g., particle diffusion and flow oscillations, is inhaled for 1.98 s through one nostril and exhaled through the other one. The bi-directional aerosol delivery with steady flow rate of 4 L/min results in deposition efficiencies (DEs) of 50.9 and 0.48% in the nasal cavity and olfactory region, respectively. Pulsatile flow with average flow rate of 4 L/min (frequency: 45 Hz) reduces these values to 34.4 and 0.12%, respectively, and it mitigates the non-uniformity of right-left deposition in both the cavity (from 1.77- to 1.33-fold) and the olfactory region (from 624- to 53.2-fold). The average drug dose deposited in the nasal cavity and the olfactory epithelium region is very similar in the right nasal cavity independent of pulsation conditions (inhalation side). In contrast, the local aerosol dose in the olfactory region of the left side is at least 100-fold lower than that in the nasal cavity independent of pulsation condition. Hence, while pulsatile flow reduces the right-left (inhalation-exhalation) imbalance, it is not able to overcome it. However, the inhalation side (even with pulsation) allows for relatively high olfactory epithelium drug doses per area reaching the same level as in the total nasal cavity. Due to the relatively low drug deposition in olfactory region on the exhalation side, this allows either very efficient targeting of the inhalation side, or uniform drug delivery by performing bidirectional flow first from the one and then from the other side of the nose.Ali FarnoudAli FarnoudAli FarnoudHesam TofighianIngo BaumannAndrew R. MartinMohammad M. RashidiMicheal P. MendenMicheal P. MendenMicheal P. MendenOtmar SchmidOtmar SchmidFrontiers Media S.A.articlenose to brain drug deliveryolfactory regionbi-directional aerosol deliverypulsatile drug deliverycomputational fluid dynamicslarge eddy simulationsTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	nose to brain drug delivery olfactory region bi-directional aerosol delivery pulsatile drug delivery computational fluid dynamics large eddy simulations Therapeutics. Pharmacology RM1-950
spellingShingle	nose to brain drug delivery olfactory region bi-directional aerosol delivery pulsatile drug delivery computational fluid dynamics large eddy simulations Therapeutics. Pharmacology RM1-950 Ali Farnoud Ali Farnoud Ali Farnoud Hesam Tofighian Ingo Baumann Andrew R. Martin Mohammad M. Rashidi Micheal P. Menden Micheal P. Menden Micheal P. Menden Otmar Schmid Otmar Schmid Pulsatile Bi-Directional Aerosol Flow Affects Aerosol Delivery to the Intranasal Olfactory Region: A Patient-Specific Computational Study
description	The nasal olfactory region is a potential route for non-invasive delivery of drugs directly from the nasal epithelium to the brain, bypassing the often impermeable blood-brain barrier. However, efficient aerosol delivery to the olfactory region is challenging due to its location in the nose. Here we explore aerosol delivery with bi-directional pulsatile flow conditions for targeted drug delivery to the olfactory region using a computational fluid dynamics (CFD) model on the patient-specific nasal geometry. Aerosols with aerodynamic diameter of 1 µm, which is large enough for delivery of large enough drug doses and yet potentially small enough for non-inertial aerosol deposition due to, e.g., particle diffusion and flow oscillations, is inhaled for 1.98 s through one nostril and exhaled through the other one. The bi-directional aerosol delivery with steady flow rate of 4 L/min results in deposition efficiencies (DEs) of 50.9 and 0.48% in the nasal cavity and olfactory region, respectively. Pulsatile flow with average flow rate of 4 L/min (frequency: 45 Hz) reduces these values to 34.4 and 0.12%, respectively, and it mitigates the non-uniformity of right-left deposition in both the cavity (from 1.77- to 1.33-fold) and the olfactory region (from 624- to 53.2-fold). The average drug dose deposited in the nasal cavity and the olfactory epithelium region is very similar in the right nasal cavity independent of pulsation conditions (inhalation side). In contrast, the local aerosol dose in the olfactory region of the left side is at least 100-fold lower than that in the nasal cavity independent of pulsation condition. Hence, while pulsatile flow reduces the right-left (inhalation-exhalation) imbalance, it is not able to overcome it. However, the inhalation side (even with pulsation) allows for relatively high olfactory epithelium drug doses per area reaching the same level as in the total nasal cavity. Due to the relatively low drug deposition in olfactory region on the exhalation side, this allows either very efficient targeting of the inhalation side, or uniform drug delivery by performing bidirectional flow first from the one and then from the other side of the nose.
format	article
author	Ali Farnoud Ali Farnoud Ali Farnoud Hesam Tofighian Ingo Baumann Andrew R. Martin Mohammad M. Rashidi Micheal P. Menden Micheal P. Menden Micheal P. Menden Otmar Schmid Otmar Schmid
author_facet	Ali Farnoud Ali Farnoud Ali Farnoud Hesam Tofighian Ingo Baumann Andrew R. Martin Mohammad M. Rashidi Micheal P. Menden Micheal P. Menden Micheal P. Menden Otmar Schmid Otmar Schmid
author_sort	Ali Farnoud
title	Pulsatile Bi-Directional Aerosol Flow Affects Aerosol Delivery to the Intranasal Olfactory Region: A Patient-Specific Computational Study
title_short	Pulsatile Bi-Directional Aerosol Flow Affects Aerosol Delivery to the Intranasal Olfactory Region: A Patient-Specific Computational Study
title_full	Pulsatile Bi-Directional Aerosol Flow Affects Aerosol Delivery to the Intranasal Olfactory Region: A Patient-Specific Computational Study
title_fullStr	Pulsatile Bi-Directional Aerosol Flow Affects Aerosol Delivery to the Intranasal Olfactory Region: A Patient-Specific Computational Study
title_full_unstemmed	Pulsatile Bi-Directional Aerosol Flow Affects Aerosol Delivery to the Intranasal Olfactory Region: A Patient-Specific Computational Study
title_sort	pulsatile bi-directional aerosol flow affects aerosol delivery to the intranasal olfactory region: a patient-specific computational study
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/784ad23d6aaa41f3aeffb11bd26bc5d2
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Pulsatile Bi-Directional Aerosol Flow Affects Aerosol Delivery to the Intranasal Olfactory Region: A Patient-Specific Computational Study

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