{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T12:51:38Z","timestamp":1792759898132,"version":"4.5.0"},"reference-count":71,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Conventional ophthalmic eye drops have low bioavailability (&lt;5%) and poor patient adherence, driving the development of sustained-release ophthalmic drug delivery systems. The lacrimal drainage system represents a unique anatomical site for minimally invasive depot formulations. Objective: To summarize and critically appraise punctal and intracanalicular drug delivery systems, occlusive devices, and in situ-forming hydrogels with respect to composition, release mechanisms, clinical efficacy, safety, and critical quality attributes (CQAs). Methods: A narrative literature review was conducted using PubMed, Scopus, Web of Science, Google Scholar, ClinicalTrials.gov, and patent\/regulatory sources, including FDA materials and Google Patents, covering 2001\u20132026. Anatomical features, materials, active pharmaceutical ingredients, release profiles, and adverse events were analyzed. Results: Seventy-one sources were included. Occlusive plugs without an active pharmaceutical ingredient demonstrate premature expulsion in up to 57.4% of cases and bacterial colonization in 44%. Drug delivery systems provide release from 7 days (PEGDA hydrogels) to 3 months (Eximore, Ocular Therapeutix\u2122). DEXTENZA\u00ae (dexamethasone) is FDA-approved for postoperative inflammation, whereas pivotal trials of travoprost (OTX-TP) and latanoprost systems (L-PPDS, EXP-LP) did not demonstrate superiority over placebo or eye drops. In situ systems eliminate size-fitting requirements but face challenges related to gelation control and biodegradation. Conclusions: We propose the following candidate CQAs: retention (&gt;80% over 4 weeks), swelling degree (30\u201360%), controlled burst release (&lt;40% within 24 h), and mechanical compatibility. The proposed QTPP matrices for punctal, intracanalicular, and in situ systems may guide the development of ophthalmic drug delivery platforms.<\/jats:p>","DOI":"10.3390\/pharmaceutics18070830","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T13:19:31Z","timestamp":1783430371000},"page":"830","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Punctal and Intracanalicular Drug Delivery Systems for Ophthalmic Use: A Narrative Review of Technologies, Clinical Outcomes, and Critical Quality Attributes"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8695-0346","authenticated-orcid":false,"given":"Elena O.","family":"Bakhrushina","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University, Moscow 119048, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8689-1225","authenticated-orcid":false,"given":"Kseniia S.","family":"Leonova","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University, Moscow 119048, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita O.","family":"Belyavsky","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University, Moscow 119048, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir I.","family":"Gegechkori","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Toxicological Chemistry, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University, Moscow 119048, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3011-9390","authenticated-orcid":false,"given":"Vasily V.","family":"Belyaev","sequence":"additional","affiliation":[{"name":"Department of Industrial Pharmacy, I.M. Sechenov First Moscow State Medical University, Moscow 119048, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9933-1808","authenticated-orcid":false,"given":"Boris B.","family":"Sysuev","sequence":"additional","affiliation":[{"name":"Faculty of Bioengineering and Bioinformatics, M.V. Lomonosov Moscow State University, Moscow 119991, Russia"},{"name":"Eurasian Academy of Good Practices (ANO \u201cUANP\u201d), Ext. Ter., Yakimanka Municipal District, Leninsky Ave., 9, Moscow 119049, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5451-0039","authenticated-orcid":false,"given":"Damir K.","family":"Salakhetdinov","sequence":"additional","affiliation":[{"name":"LLC \u201cChemical Diversity Research Institute\u201d, Khimki 141401, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan I.","family":"Krasnyuk","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University, Moscow 119048, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenia L.","family":"Atkova","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Institution of Science \u201cM.M. Krasnov Research Institute of Eye Diseases\u201d 11A, Rossolimo Street, Moscow 119021, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2990-8111","authenticated-orcid":false,"given":"Vasily D.","family":"Yartsev","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Institution of Science \u201cM.M. Krasnov Research Institute of Eye Diseases\u201d 11A, Rossolimo Street, Moscow 119021, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9221","DOI":"10.2147\/IJN.S532074","article-title":"Nanomedicine-Based Ophthalmic Drug Delivery Systems for the Treatment of Ocular Diseases","volume":"20","author":"Lin","year":"2025","journal-title":"Int. J. Nanomed."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Wang, Y., and Wang, C. (2022). 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