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The PPAR\u03b1 agonist fenofibrate (Feno) has shown therapeutic potential in diabetic corneal disease, but prior topical and oral approaches still face formulation and translational limitations. In this study, we developed a Feno-loaded microemulsion (Feno microemulsion) eyedrop to improve drug solubility, precorneal residence, and ocular bioavailability of Feno for the treatment of DK. Potential excipients were first screened in primary human corneal epithelial cells (HCECs) to identify components that were well tolerated and did not interfere with epithelial migration. Using the optimized excipients, a stable oil-in-water microemulsion was formulated with high drug loading, nanosized droplets, favorable shear-thinning rheology, and excellent physicochemical stability over 12 months. The optimized formulation showed good ocular tolerability, prolonged ocular surface retention, and sustained drug exposure in tear fluid and ocular tissues with minimal systemic absorption. Under high-glucose and oxidative stress conditions, Feno microemulsion enhanced HCEC migration, restored mitochondrial respiration and ATP production, and increased the expression of PPAR\u03b1-associated mitochondrial markers. In vivo, topical Feno microemulsion significantly accelerated corneal epithelial wound healing in both streptozotocin-induced (type 1 diabetic) and db\/db (type 2 diabetic) mouse models and also improved early-stage healing in nondiabetic controls. Overall, these findings identify Feno microemulsion as a safe and effective topical platform for DK and support its therapeutic benefit through preservation of corneal mitochondrial function and promotion of epithelial wound healing.<\/jats:p>","DOI":"10.1021\/acsami.6c16373","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:22:30Z","timestamp":1788276150000},"page":"54702-54719","source":"Crossref","is-referenced-by-count":0,"title":["Microemulsion Eyedrop for Delivery of a PPAR\u03b1 Agonist To Improve Diabetic Keratopathy Corneal Wound Healing"],"prefix":"10.1021","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1903-6690","authenticated-orcid":true,"given":"Ehsan","family":"Kaffash","sequence":"first","affiliation":[{"name":"Virginia Commonwealth University , , , ,","place":["Richmond, Virginia, United States, 23298"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0609-6280","authenticated-orcid":true,"given":"Wentao","family":"Liang","sequence":"additional","affiliation":[{"name":"Wake Forest University School of Medicine , , , ,","place":["Winston-Salem, North Carolina, United States, 27101"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudra","family":"Pangeni","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University , , , ,","place":["Richmond, Virginia, United States, 23298"]},{"name":"Philadelphia College of Osteopathic Medicine , , , ,","place":["Suwanee, Georgia, United States, 30024"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Clayton","sequence":"additional","affiliation":[{"name":"Wake Forest University School of Medicine , , , ,","place":["Winston-Salem, North Carolina, United States, 27101"]},{"name":"University of Tennessee Health Science Center , , , ,","place":["Memphis, Tennessee, United States, 38163"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8782-8561","authenticated-orcid":true,"given":"Tianyi","family":"Li","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University , , , ,","place":["Richmond, Virginia, United States, 23298"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sagun","family":"Poudel","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University , , , ,","place":["Richmond, Virginia, United States, 23298"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiya","family":"Han","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University , , , ,","place":["Richmond, Virginia, United States, 23298"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Zhao","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University , , , ,","place":["Richmond, Virginia, United States, 23298"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-xing","family":"Ma","sequence":"additional","affiliation":[{"name":"Wake Forest University School of Medicine , , , ,","place":["Winston-Salem, North Carolina, United States, 27101"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3191-0771","authenticated-orcid":true,"given":"Qingguo","family":"Xu","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University , , , ,","place":["Richmond, Virginia, United States, 23298"]},{"name":"Virginia Commonwealth University , , , ,","place":["Richmond, Virginia, United States, 23298"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"issue":"6","key":"2026101406070063100_cit1","doi-asserted-by":"publisher","first-page":"2058","DOI":"10.1016\/j.ajpath.2012.08.029","article-title":"Reduced Innervation and Delayed Re-Innervation After Epithelial Wounding in Type 2 Diabetic Goto-Kakizaki Rats","volume":"181","author":"Wang","year":"2012","journal-title":"Am. 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