{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:58:29Z","timestamp":1790657909904,"version":"4.1.0"},"reference-count":100,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Intranasal hydrogels offer a strategy to address rapid mucociliary clearance, limited nasal residence, difficult payload properties, and insufficient brain exposure in Alzheimer\u2019s disease (AD). This Review evaluates hydrogel and hydrogel-associated systems across formulation architecture, nasal-interface performance, brain pharmacokinetics, pharmacodynamics, safety, and translation. Selected systems improved deposition or retention, controlled release, permeation, and central exposure relative to relevant comparators, with some also showing convergent behavioral and disease-relevant biological effects in preclinical models. The strongest evidence comes from matched comparisons that distinguish route effects from the incremental contributions of carriers and hydrogels. However, rheology, deposition, targeting metrics, statistical reporting, complete-product stability, repeated-dose safety, device performance, and human reproducibility remain inconsistently characterized. Overall, the evidence supports intranasal hydrogels as a credible preclinical platform for brain-directed AD drug delivery, but not as clinically validated therapy, and favors standardized, device-integrated, comparator-resolved development.<\/jats:p>","DOI":"10.3389\/fphar.2026.1960603","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:33:29Z","timestamp":1790656409000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Intranasal hydrogels for Alzheimer\u2019s disease: from nasal-interface engineering to brain targeting and translational readiness"],"prefix":"10.3389","volume":"17","author":[{"given":"Hossein","family":"Omidian","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Barry and Judy Silverman College of Pharmacy, Nova Southeastern University","place":["Fort Lauderdale, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi X.","family":"Cubeddu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Barry and Judy Silverman College of Pharmacy, Nova Southeastern University","place":["Fort Lauderdale, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"124814","DOI":"10.1016\/j.ijpharm.2024.124814","article-title":"Dihydroquercetin nanoparticles nasal gel is a promising formulation for amelioration of alzheimer's disease","volume":"666","author":"Abou-Taleb","year":"2024","journal-title":"Int. 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