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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| Veröffentlicht in: | PloS one 2021-01, Vol.16 (1), p.e0246007-e0246007 |
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| creator | Shang, Yidan Inthavong, Kiao Qiu, Dasheng Singh, Narinder He, Fajiang Tu, Jiyuan |
| 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. |
| doi_str_mv | 10.1371/journal.pone.0246007 |
| format | Article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0246007</identifier><identifier>PMID: 33507973</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Absorption ; Absorption (Physiology) ; Air flow ; Air transportation ; Aircraft ; Bioequivalence ; Biology and Life Sciences ; Chemical properties ; Computational fluid dynamics ; Computed tomography ; Computer applications ; Deposition ; Drug delivery ; Engineering ; Engineering schools ; Fluid dynamics ; Funding ; Head and neck ; Image reconstruction ; Intranasal medication ; Medicine ; Medicine and Health Sciences ; Mucosa ; Mucus ; Nasal mucosa ; Nose ; Nuclear engineering ; Nuclear medicine ; Nuclear safety ; Otolaryngology ; Particle size ; Particle size distribution ; Particle trajectories ; Pharmacology, Experimental ; Physical Sciences ; Physicochemical properties ; Physiological aspects ; Positron emission ; Positron emission tomography ; Product safety ; Regions ; Regulators ; Simulation ; Sinuses ; Size distribution ; Surgery ; Velocity</subject><ispartof>PloS one, 2021-01, Vol.16 (1), p.e0246007-e0246007</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Shang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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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.</description><subject>Absorption</subject><subject>Absorption (Physiology)</subject><subject>Air flow</subject><subject>Air transportation</subject><subject>Aircraft</subject><subject>Bioequivalence</subject><subject>Biology and Life Sciences</subject><subject>Chemical properties</subject><subject>Computational fluid dynamics</subject><subject>Computed tomography</subject><subject>Computer applications</subject><subject>Deposition</subject><subject>Drug delivery</subject><subject>Engineering</subject><subject>Engineering schools</subject><subject>Fluid dynamics</subject><subject>Funding</subject><subject>Head and neck</subject><subject>Image reconstruction</subject><subject>Intranasal medication</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Mucosa</subject><subject>Mucus</subject><subject>Nasal 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Fang-Bao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prediction of nasal spray drug absorption influenced by mucociliary clearance</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2021-01-28</date><risdate>2021</risdate><volume>16</volume><issue>1</issue><spage>e0246007</spage><epage>e0246007</epage><pages>e0246007-e0246007</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33507973</pmid><doi>10.1371/journal.pone.0246007</doi><orcidid>https://orcid.org/0000-0002-7719-1832</orcidid><orcidid>https://orcid.org/0000-0003-0476-0237</orcidid><oa>free_for_read</oa></addata></record> |
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| source | DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Absorption Absorption (Physiology) Air flow Air transportation Aircraft Bioequivalence Biology and Life Sciences Chemical properties Computational fluid dynamics Computed tomography Computer applications Deposition Drug delivery Engineering Engineering schools Fluid dynamics Funding Head and neck Image reconstruction Intranasal medication Medicine Medicine and Health Sciences Mucosa Mucus Nasal mucosa Nose Nuclear engineering Nuclear medicine Nuclear safety Otolaryngology Particle size Particle size distribution Particle trajectories Pharmacology, Experimental Physical Sciences Physicochemical properties Physiological aspects Positron emission Positron emission tomography Product safety Regions Regulators Simulation Sinuses Size distribution Surgery Velocity |
| title | Prediction of nasal spray drug absorption influenced by mucociliary clearance |
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