{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:29:22Z","timestamp":1785403762117,"version":"3.56.0"},"reference-count":41,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Thaksin University Research Fund under the Researcher Capacity Development Grant Program, Fiscal Year 2026, New Researcher Development Category"},{"id":[{"id":"https:\/\/ror.org\/00t2prd39","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Rebamipide (REB) is a poorly water-soluble drug with limited ocular bioavailability, necessitating advanced delivery strategies for sustained therapy in dry eye disease. Methods: In the present study, micelle-assisted ocular inserts were developed using non-ionic surfactants to enhance REB solubilization, drug loading, and controlled ocular delivery. The intrinsic solubility of REB in simulated tear fluid (STF, pH 7.4) was evaluated and compared with micellar systems. The formulations were characterized for particle size, polydispersity index, and zeta potential. Ocular inserts were fabricated via UV photopolymerization and evaluated for physicochemical properties, drug content, in vitro drug release, ex vivo permeation, cytocompatibility using SIRC cells, and histopathological analysis. Results: REB exhibited low intrinsic solubility in STF (26.05 \u00b1 1.00 \u00b5g\/mL), which was significantly enhanced in micellar systems, particularly with Solutol HS 15 (306.71 \u00b1 1.10 \u00b5g\/mL) and Tween 80 (263.18 \u00b1 1.19 \u00b5g\/mL). All micellar formulations formed stable nanosized micelles (7.5\u201315.1 nm) with low polydispersity (PDI &lt; 0.35) and near-neutral zeta potential (\u22120.08 to \u22122.81 mV). The prepared ocular inserts showed uniform thickness, weight, and physiological surface pH. Micelle-assisted inserts demonstrated significantly higher drug content (87.40 \u00b1 3.25 to 99.19 \u00b1 2.44 \u00b5g\/insert) compared to plain REB inserts (21.41 \u00b1 2.28 \u00b5g\/insert). In- vitro studies revealed sustained drug release over 24 h (92.25 \u00b1 1.64 to 100.50 \u00b1 1.10%), whereas plain inserts showed burst release. Ex vivo permeation studies indicated enhanced drug permeation (up to 77.30 \u00b1 0.34 \u00b5g) and improved flux (1.38\u20138.52 \u00b5g\/cm2\u00b7h) compared to plain REB. Cytocompatibility studies confirmed &gt;90% SIRC cell viability, and histopathological analysis showed no structural damage to corneal tissue. Conclusions: Micelle-assisted ocular inserts, particularly those formulated with Solutol HS 15 and Tween 80, provide a promising platform for sustained, safe, and effective ocular delivery of Rebamipide in the management of dry eye disease.<\/jats:p>","DOI":"10.3390\/pharmaceutics18050578","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T12:15:07Z","timestamp":1778156107000},"page":"578","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Micelle-Based Ocular Inserts for Sustained Delivery and Improved Corneal Permeation of Rebamipide in Dry Eye Disease"],"prefix":"10.3390","volume":"18","author":[{"given":"Yashkumar","family":"Patel","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Technology, L. M. College of Pharmacy, Ahmedabad 380009, Gujarat, India"},{"name":"Research Scholar, PhD Section (Pharmacy), Gujarat Technological University, Ahmedabad 382424, Gujarat, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3865-8855","authenticated-orcid":false,"given":"Ketan M.","family":"Ranch","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Technology, L. M. College of Pharmacy, Ahmedabad 380009, Gujarat, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6068-0616","authenticated-orcid":false,"given":"Anilkumar","family":"Prajapati","sequence":"additional","affiliation":[{"name":"Research Scholar, PhD Section (Pharmacy), Gujarat Technological University, Ahmedabad 382424, Gujarat, India"},{"name":"Department of Pharmacology, L. M. College of Pharmacy, Ahmedabad 380009, Gujarat, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2616-8265","authenticated-orcid":false,"given":"Harshilkumar","family":"Jani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Technology, L. M. College of Pharmacy, Ahmedabad 380009, Gujarat, India"},{"name":"Research Scholar, PhD Section (Pharmacy), Gujarat Technological University, Ahmedabad 382424, Gujarat, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julalak Chorachoo","family":"Ontong","sequence":"additional","affiliation":[{"name":"Cosmetic Technology and Dietary Supplement Products Program, Faculty of Agro and Bio Industry, Thaksin University, Ban Pa Phayom 93210, Phatthalung, Thailand"},{"name":"High-Value Bioproduct Innovation Research Center, Faculty of Agro and Bio Industry, Thaksin University, Ban Pa Phayom 93210, Phatthalung, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7929-3322","authenticated-orcid":false,"given":"Sudarshan","family":"Singh","sequence":"additional","affiliation":[{"name":"Office of Research Administration, Chiang Mai University, Chiang Mai 50200, Chiang Mai, Thailand"},{"name":"Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Chiang Mai, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"ref_1","first-page":"71","article-title":"The Pathophysiology, Diagnosis, and Treatment of Dry Eye Disease","volume":"112","author":"Messmer","year":"2015","journal-title":"Dtsch. 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