{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:53:48Z","timestamp":1790949228751,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The nasal epithelium is an important target for drug delivery to the nose and secondary organs such as the brain via the olfactory bulb. For both topical and brain delivery, the targeting of specific nasal regions such as the olfactory epithelium (brain) is essential, yet challenging. In this study, a numerical model was developed to predict the regional dose as mass per surface area (for an inhaled mass of 2.5 mg), which is the biologically most relevant dose metric for drug delivery in the respiratory system. The role of aerosol diameter (particle diameter: 1 nm to 30 \u00b5m) and inhalation flow rate (4, 15 and 30 L\/min) in optimal drug delivery to the vestibule, nasal valve, olfactory and nasopharynx is assessed. To obtain the highest doses in the olfactory region, we suggest aerosols with a diameter of 20 \u00b5m and a medium inlet air flow rate of 15 L\/min. High deposition on the olfactory epithelium was also observed for nanoparticles below 1 nm, as was high residence time (slow flow rate of 4 L\/min), but the very low mass of 1 nm nanoparticles is prohibitive for most therapeutic applications. Moreover, high flow rates (30 L\/min) and larger micro-aerosols lead to highest doses in the vestibule and nasal valve regions. On the other hand, the highest drug doses in the nasopharynx are observed for nano-aerosol (1 nm) and fine microparticles (1\u201320 \u00b5m) with a relatively weak dependence on flow rate. Furthermore, using the 45 different inhalation scenarios generated by numerical models, different machine learning models with five-fold cross-validation are trained to predict the delivered dose and avoid partial differential equation solvers for future predictions. Random forest and gradient boosting models resulted in R2 scores of 0.89 and 0.96, respectively. The aerosol diameter and region of interest are the most important features affecting delivered dose, with an approximate importance of 42% and 47%, respectively.<\/jats:p>","DOI":"10.3390\/ph16010081","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T07:05:09Z","timestamp":1673247909000},"page":"81","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Numerical and Machine Learning Analysis of the Parameters Affecting the Regionally Delivered Nasal Dose of Nano- and Micro-Sized Aerosolized Drugs"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9298-5497","authenticated-orcid":false,"given":"Ali","family":"Farnoud","sequence":"first","affiliation":[{"name":"Computational Health Center, Helmholtz Munich, 85764 Neuherberg, Germany"},{"name":"Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL), 81377 Munich, Germany"},{"name":"Institute of Lung Health and Immunity, Helmholtz Zentrum M\u00fcnchen\u2013German Research Center for Environmental Health, 85764 Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9903-3985","authenticated-orcid":false,"given":"Hesam","family":"Tofighian","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, Amirkabir University of Technology, Tehran 1591634311, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6945-2601","authenticated-orcid":false,"given":"Ingo","family":"Baumann","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Medical Center of Heidelberg University, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1789-2303","authenticated-orcid":false,"given":"Kaveh","family":"Ahookhosh","sequence":"additional","affiliation":[{"name":"Biomedical MRI and MoSAIC, Department of Imaging and Pathology, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oveis","family":"Pourmehran","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery, Adelaide Medical School, The University of Adelaide, Adelaide 5011, Australia"},{"name":"School of Mechanical Engineering, The University of Adelaide, Adelaide 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinguang","family":"Cui","sequence":"additional","affiliation":[{"name":"School of Aerospace Engineering, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Heuveline","sequence":"additional","affiliation":[{"name":"Engineering Mathematics and Computing Lab (EMCL), Heidelberg University, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3775-8184","authenticated-orcid":false,"given":"Chen","family":"Song","sequence":"additional","affiliation":[{"name":"Engineering Mathematics and Computing Lab (EMCL), Heidelberg University, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Vreugde","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery, Adelaide Medical School, The University of Adelaide, Adelaide 5011, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter-John","family":"Wormald","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery, Adelaide Medical School, The University of Adelaide, Adelaide 5011, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0267-5792","authenticated-orcid":false,"given":"Michael P.","family":"Menden","sequence":"additional","affiliation":[{"name":"Computational Health Center, Helmholtz Munich, 85764 Neuherberg, Germany"},{"name":"Department of Biology, Ludwig-Maximilian University Munich, 82152 Planegg, Germany"},{"name":"German Center for Diabetes Research (DZD e.V.), 85764 Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8012-7786","authenticated-orcid":false,"given":"Otmar","family":"Schmid","sequence":"additional","affiliation":[{"name":"Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL), 81377 Munich, Germany"},{"name":"Institute of Lung Health and Immunity, Helmholtz Zentrum M\u00fcnchen\u2013German Research Center for Environmental Health, 85764 Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1007\/s13346-012-0121-z","article-title":"Current understanding of nasal morphology and physiology as a drug delivery target","volume":"3","author":"Suman","year":"2013","journal-title":"Drug Deliv. 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