{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:27:24Z","timestamp":1791235644236,"version":"4.1.0"},"reference-count":126,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:00:00Z","timestamp":1675814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Smart Injectable Drug-Delivery systems for Parkinson\u2019s and. Alzheimer\u2019s Disease Treatment\u2014PAD-INJ","award":["772168"],"award-info":[{"award-number":["772168"]}]},{"name":"European Research Council","award":["772168"],"award-info":[{"award-number":["772168"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Intranasal (IN) drug delivery is a non-invasive and effective route for the administration of drugs to the brain at pharmacologically relevant concentrations, bypassing the blood\u2013brain barrier (BBB) and minimizing adverse side effects. IN drug delivery can be particularly promising for the treatment of neurodegenerative diseases. The drug delivery mechanism involves the initial drug penetration through the nasal epithelial barrier, followed by drug diffusion in the perivascular or perineural spaces along the olfactory or trigeminal nerves, and final extracellular diffusion throughout the brain. A part of the drug may be lost by drainage through the lymphatic system, while a part may even enter the systemic circulation and reach the brain by crossing the BBB. Alternatively, drugs can be directly transported to the brain by axons of the olfactory nerve. To improve the effectiveness of drug delivery to the brain by the IN route, various types of nanocarriers and hydrogels and their combinations have been proposed. This review paper analyzes the main biomaterials-based strategies to enhance IN drug delivery to the brain, outlining unsolved challenges and proposing ways to address them.<\/jats:p>","DOI":"10.3390\/ijms24043390","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T06:00:05Z","timestamp":1675836005000},"page":"3390","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["Biomaterials-Enhanced Intranasal Delivery of Drugs as a Direct Route for Brain Targeting"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4124-463X","authenticated-orcid":false,"given":"Elena","family":"Marcello","sequence":"first","affiliation":[{"name":"Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca Degli Abruzzi 24, 10129 Turin, Italy"},{"name":"Interuniversity Center for the Promotion of 3Rs Principles in Teaching and Research, Centro 3R, 56122 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2067-7732","authenticated-orcid":false,"given":"Valeria","family":"Chiono","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca Degli Abruzzi 24, 10129 Turin, Italy"},{"name":"Interuniversity Center for the Promotion of 3Rs Principles in Teaching and Research, Centro 3R, 56122 Pisa, Italy"},{"name":"Institute for Chemical-Physical Processes, National Research Council (CNR-IPCF), 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.2174\/157015908785777210","article-title":"V Brain Endothelial Cell-Cell Junctions: How to \u201cOpen\u201d the Blood Brain Barrier","volume":"6","author":"Stamatovic","year":"2008","journal-title":"Curr. 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