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Prediction of nasal spray drug absorption influenced by mucociliary clearance

Evaluation of nasal spray drug absorption has been challenging because deposited particles are consistently transported away by mucociliary clearance during diffusing through the mucus layer. This study developed a novel approach combining Computational Fluid Dynamics (CFD) techniques with a 1-D muc...

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Autores principales: Shang, Yidan, Inthavong, Kiao, Qiu, Dasheng, Singh, Narinder, He, Fajiang, Tu, Jiyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842989/
https://www.ncbi.nlm.nih.gov/pubmed/33507973
http://dx.doi.org/10.1371/journal.pone.0246007
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author Shang, Yidan
Inthavong, Kiao
Qiu, Dasheng
Singh, Narinder
He, Fajiang
Tu, Jiyuan
author_facet Shang, Yidan
Inthavong, Kiao
Qiu, Dasheng
Singh, Narinder
He, Fajiang
Tu, Jiyuan
author_sort Shang, Yidan
collection PubMed
description Evaluation of nasal spray drug absorption has been challenging because deposited particles are consistently transported away by mucociliary clearance during diffusing through the mucus layer. This study developed a novel approach combining Computational Fluid Dynamics (CFD) techniques with a 1-D mucus diffusion model to better predict nasal spray drug absorption. This integrated CFD-diffusion approach comprised a preliminary simulation of nasal airflow, spray particle injection, followed by analysis of mucociliary clearance and drug solute diffusion through the mucus layer. The spray particle deposition distribution was validated experimentally and numerically, and the mucus velocity field was validated by comparing with previous studies. Total and regional drug absorption for solute radius in the range of 1 − 110nm were investigated. The total drug absorption contributed by the spray particle deposition was calculated. The absorption contribution from particles that deposited on the anterior region was found to increase significantly as the solute radius became larger (diffusion became slower). This was because the particles were consistently moved out of the anterior region, and the delayed absorption ensured more solute to be absorbed by the posterior regions covered with respiratory epithelium. Future improvements in the spray drug absorption model were discussed. The results of this study are aimed at working towards a CFD-based integrated model for evaluating nasal spray bioequivalence.
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spelling pubmed-78429892021-02-04 Prediction of nasal spray drug absorption influenced by mucociliary clearance Shang, Yidan Inthavong, Kiao Qiu, Dasheng Singh, Narinder He, Fajiang Tu, Jiyuan PLoS One Research Article Evaluation of nasal spray drug absorption has been challenging because deposited particles are consistently transported away by mucociliary clearance during diffusing through the mucus layer. This study developed a novel approach combining Computational Fluid Dynamics (CFD) techniques with a 1-D mucus diffusion model to better predict nasal spray drug absorption. This integrated CFD-diffusion approach comprised a preliminary simulation of nasal airflow, spray particle injection, followed by analysis of mucociliary clearance and drug solute diffusion through the mucus layer. The spray particle deposition distribution was validated experimentally and numerically, and the mucus velocity field was validated by comparing with previous studies. Total and regional drug absorption for solute radius in the range of 1 − 110nm were investigated. The total drug absorption contributed by the spray particle deposition was calculated. The absorption contribution from particles that deposited on the anterior region was found to increase significantly as the solute radius became larger (diffusion became slower). This was because the particles were consistently moved out of the anterior region, and the delayed absorption ensured more solute to be absorbed by the posterior regions covered with respiratory epithelium. Future improvements in the spray drug absorption model were discussed. The results of this study are aimed at working towards a CFD-based integrated model for evaluating nasal spray bioequivalence. Public Library of Science 2021-01-28 /pmc/articles/PMC7842989/ /pubmed/33507973 http://dx.doi.org/10.1371/journal.pone.0246007 Text en © 2021 Shang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Shang, Yidan
Inthavong, Kiao
Qiu, Dasheng
Singh, Narinder
He, Fajiang
Tu, Jiyuan
Prediction of nasal spray drug absorption influenced by mucociliary clearance
title Prediction of nasal spray drug absorption influenced by mucociliary clearance
title_full Prediction of nasal spray drug absorption influenced by mucociliary clearance
title_fullStr Prediction of nasal spray drug absorption influenced by mucociliary clearance
title_full_unstemmed Prediction of nasal spray drug absorption influenced by mucociliary clearance
title_short Prediction of nasal spray drug absorption influenced by mucociliary clearance
title_sort prediction of nasal spray drug absorption influenced by mucociliary clearance
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842989/
https://www.ncbi.nlm.nih.gov/pubmed/33507973
http://dx.doi.org/10.1371/journal.pone.0246007
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