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The unique anatomy of the nose-brain interface facilitates direct drug transport via the olfactory and trigeminal pathways to the brain, bypassing the blood\u2013brain barrier. Different administration techniques as well as advanced drug formulations like targeted nanoparticles and thermoresponsive systems have been explored to improve the delivery efficiency and the therapeutic efficacy. This review provides an up-to-date perspective on this fast-developing field, and discusses different studies on safety and pharmacokinetic properties. A thorough evaluation of preclinical and clinical studies reveals both promises and challenges of this delivery method, highlighting approved drugs for the treatment of epilepsy and migraine that successfully utilize intranasal routes. The current landscape of research on nose-to-brain delivery is critically discussed, and a rationale is provided for ongoing research to optimize therapeutic strategies.<\/jats:p>","DOI":"10.1186\/s40035-025-00481-w","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T08:17:10Z","timestamp":1747642630000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":130,"title":["Nose-to-brain drug delivery: from bench to bedside"],"prefix":"10.1186","volume":"14","author":[{"given":"Isabell","family":"Drath","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Richter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8670-5495","authenticated-orcid":false,"given":"Malte","family":"Feja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,19]]},"reference":[{"issue":"1","key":"481_CR1","doi-asserted-by":"publisher","first-page":"e1768","DOI":"10.1002\/wnan.1768","volume":"14","author":"P Kiran","year":"2022","unstructured":"Kiran P, Debnath SK, Neekhra S, Pawar V, Khan A, Dias F, et al. 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