{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T10:16:36Z","timestamp":1783073796028,"version":"3.54.6"},"reference-count":52,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T00:00:00Z","timestamp":1782518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Non-invasive drug delivery for ocular diseases remains a significant challenge in ophthalmology, as conventional eye drops offer less than 5% bioavailability due to pre-corneal barriers and the corneal epithelium. This review explores the intranasal (IN) route as a promising strategy for targeting both the anterior and posterior segments of the eye. The IN route leverages several distinct pathways: the nasolacrimal reflex for remote physiological stimulation; the \u201cneural bridge\u201d through the cribriform plate, allowing direct perineural and vascular transport via the olfactory and trigeminal nerves to bypass the blood\u2013retinal barrier; and systemic absorption that avoids hepatic first-pass metabolism. Pre-clinical evidence indicates that IN administration of agents such as erythropoietin, nerve growth factor, and insulin achieves superior retinal concentrations compared to topical or systemic dosing, offering neuroprotection in models of retinal degeneration and glaucoma. Clinically, varenicline nasal spray is already FDA-approved for dry eye disease, while intranasal steroids demonstrate a favorable ocular safety profile without significantly increasing intraocular pressure. Although limited by mucociliary clearance and small delivery volumes, the IN route offers a painless, non-invasive alternative to intraocular injections, potentially enhancing patient compliance. Future advancements in mucoadhesive nanocarriers are essential to optimize drug residence time and realize the full potential of nose-to-eye delivery in chronic ophthalmic care.<\/jats:p>","DOI":"10.3390\/jcm15135029","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T08:45:20Z","timestamp":1782722720000},"page":"5029","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nose-to-Eye Delivery: The Potential of Intranasal Administration in Ophthalmology"],"prefix":"10.3390","volume":"15","author":[{"given":"Maria Letizia","family":"Adezio","sequence":"first","affiliation":[{"name":"Department of Sense Organs, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8532-4578","authenticated-orcid":false,"given":"Danilo","family":"Iannetta","sequence":"additional","affiliation":[{"name":"Department of Sense Organs, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Manni","sequence":"additional","affiliation":[{"name":"Department of Sense Organs, Sapienza University of Rome, 00185 Rome, Italy"},{"name":"IRCCS\u2014Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6152-433X","authenticated-orcid":false,"given":"Giacomo","family":"Visioli","sequence":"additional","affiliation":[{"name":"Department of Sense Organs, Sapienza University of Rome, 00185 Rome, Italy"},{"name":"Ophtalmology Unit, San Giovanni Addolorata Hospital, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Roberti","sequence":"additional","affiliation":[{"name":"Department of Sense Organs, Sapienza University of Rome, 00185 Rome, Italy"},{"name":"IRCCS\u2014Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5366-882X","authenticated-orcid":false,"given":"Ludovico","family":"Alisi","sequence":"additional","affiliation":[{"name":"Department of Sense Organs, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lucchino, L., Giuliano, E., Giuliano, F., Chiorrini, R., Semeraro, F., Drago, L., Ferrara, M., and Romano, V. 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