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However, the blood\u2013brain barrier (BBB) presents a significant obstacle to the effective treatment of these CNS disorders, limiting the ability of therapeutic agents to reach the brain. In this context, intranasal drug delivery, which bypasses the BBB, has attracted considerable attention in recent years. By utilizing pathways such as the olfactory and trigeminal nerves, intranasal drug delivery facilitates the rapid transport of drugs to the brain, thereby enhancing both the bioavailability and targeting efficiency of the drugs. This review provides an overview of the molecular mechanisms underlying intranasal drug delivery, its advancements in the treatment of CNS diseases, strategies to improve delivery efficiency, and a discussion of the challenges and potential future directions in this field. The aim of this paper is to offer valuable insights and guidance for researchers and clinicians working in the area of CNS disease treatment.<\/jats:p>","DOI":"10.3390\/pharmaceutics17060775","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T14:03:11Z","timestamp":1750082591000},"page":"775","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Intranasal Drug Delivery Technology in the Treatment of Central Nervous System Diseases: Challenges, Advances, and Future Research Directions"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1536-634X","authenticated-orcid":false,"given":"Xunxun","family":"Wu","sequence":"first","affiliation":[{"name":"School of Medicine, Huaqiao University, Quanzhou 362021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranqing","family":"Zang","sequence":"additional","affiliation":[{"name":"School of Medicine, Huaqiao University, Quanzhou 362021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiting","family":"Qiu","sequence":"additional","affiliation":[{"name":"School of Medicine, Huaqiao University, Quanzhou 362021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufang","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine, Huaqiao University, Quanzhou 362021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbin","family":"Peng","sequence":"additional","affiliation":[{"name":"School of Medicine, Huaqiao University, Quanzhou 362021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyun","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Medicine, Huaqiao University, Quanzhou 362021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Site","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Medicine, Huaqiao University, Quanzhou 362021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiyan","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medicine, Huaqiao University, Quanzhou 362021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0633-1906","authenticated-orcid":false,"given":"Yong","family":"Diao","sequence":"additional","affiliation":[{"name":"School of Medicine, Huaqiao University, Quanzhou 362021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.jconrel.2018.05.011","article-title":"Nose-to-brain drug delivery: An update on clinical challenges and progress towards approval of anti-Alzheimer drugs","volume":"281","author":"Agrawal","year":"2018","journal-title":"J. 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