{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T17:03:02Z","timestamp":1785171782128,"version":"3.55.0"},"reference-count":301,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"High-Quality Clinical Research Fund of Tongji Hospital","award":["2024TJCR013"],"award-info":[{"award-number":["2024TJCR013"]}]},{"name":"Integrated Chinese and Western Medicine Project for Chronic Disease Management","award":["CXZH2024014"],"award-info":[{"award-number":["CXZH2024014"]}]},{"name":"Interdisciplinarity Research Program of Huazhong University of Science and Technology","award":["2023JCYJ030"],"award-info":[{"award-number":["2023JCYJ030"]}]},{"name":"Medical Innovation and Transformation Incubation Project of Tongji Hospital","award":["2022CXZH010"],"award-info":[{"award-number":["2022CXZH010"]}]},{"name":"Chutian Talent Programme\u2014Science and Technology Innovation Team"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Disorders of the central nervous system (CNS) are intricate and often resistant conditions that create a significant global impact, affecting millions of individuals each year. The blood\u2013brain barrier (BBB) acts as a protective mechanism for the brain against external substances, but it also prevents most therapeutic agents from entering the CNS, leading to inadequate drug absorption and reduced effectiveness after diagnosis. Nasal drug delivery has emerged as a viable approach to bypass the BBB, facilitating direct access to the brain through the olfactory and trigeminal nerve routes. Although considerable research focuses on innovative nasal formulations with proven clinical promise, a critical gap persists: a systematic framework that bridges laboratory breakthroughs with clinical implementation. This review addresses this unmet need by integrating recent basic research advances with practical clinical requirements. We summarize nasal transport pathways, targeted design strategies, formulation optimization, and device engineering. Crucially, we propose a structured clinical evaluation framework built upon five essential pillars: targeting precision, pharmacokinetic performance, multi-organ safety profiling, device\u2013drug clinical compatibility, and anatomical translation from animal models to humans. By mapping current research capabilities against clinical readiness criteria, this framework identifies translational bottlenecks and provides actionable guidance to accelerate the bench-to-bedside transition of intranasal drug delivery systems for CNS disorders.<\/jats:p>","DOI":"10.3390\/pharmaceutics18080916","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T16:11:56Z","timestamp":1785168716000},"page":"916","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systematic Design and Evaluation of Nasal Drug Delivery for Central Nervous System Disease from Experimental to Clinical Application"],"prefix":"10.3390","volume":"18","author":[{"given":"Xi-Rui","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1668-6604","authenticated-orcid":false,"given":"Ziyue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Provincial Clinical Research Center for Stroke, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8518-1159","authenticated-orcid":false,"given":"Wensheng","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Provincial Clinical Research Center for Stroke, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyuan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Provincial Clinical Research Center for Stroke, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Provincial Clinical Research Center for Stroke, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s10194-026-02281-7","article-title":"WHO\u2019s Global status report on neurology: Mixed messages for people with headache disorders","volume":"27","author":"Steiner","year":"2026","journal-title":"J. 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