{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T16:03:15Z","timestamp":1779724995752,"version":"3.53.1"},"reference-count":65,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006407","name":"Natural Science Foundation of Henan Province","doi-asserted-by":"publisher","award":["252300423780"],"award-info":[{"award-number":["252300423780"]}],"id":[{"id":"10.13039\/501100006407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006407","name":"Natural Science Foundation of Henan Province","doi-asserted-by":"publisher","award":["252300423781"],"award-info":[{"award-number":["252300423781"]}],"id":[{"id":"10.13039\/501100006407","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Henan Eye Hospital Basic Science Research Program","award":["22JCQN008"],"award-info":[{"award-number":["22JCQN008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Vernal keratoconjunctivitis (VKC) is a chronic, recurrent allergic disease with the risk of permanent injury or visual disabilities. Tacrolimus (FK506) is a potent immunosuppressant with insoluble ability and a high molecular weight. Methods: To address this disease, we successfully prepared FK506-loaded polymeric micelles (0.01%, FK506-MS) by a simple, organic solvent-free method. The physicochemical properties of FK506-MS were characterized. Corneal permeability, biocompatibility, and bioavailability were evaluated in vitro and in vivo in comparison with a commercially available FK506 suspension (0.1%, FK506-Susp). Therapeutic efficacy was also assessed in a murine model of VKC. Results: FK506-MS exhibited a small, homogeneous particle size with near-neutral surface charge. FK506-MS displayed a rapid and sustained release, along with excellent biocompatibility and stability. Ocular pharmacokinetic studies in rabbits revealed that FK506-MS, despite being only one-tenth the concentration of FK506-Susp, could achieve sufficient concentration in the conjunctiva with a prolonged half-life (T1\/2) while systemic exposure in blood was markedly reduced. FK506-MS elicited comparable therapeutic responses across evaluated parameters: clinical symptoms, molecular biomarkers of inflammation, and histopathological findings. Conclusions: The dose-sparing advantage of FK506-MS suggests that the conventional paradigm of concentration-dependent therapeutic efficacy may require further refinement. The nanomicellar delivery system not only overcomes the solubility limitation of FK506 but also exhibits a potential therapeutic paradigm: achieving comparable clinical efficacy with a lower dose and reduced systemic exposure. These results provide a promising preclinical basis for the potential development of a topical tacrolimus therapy that may offer improved safety, cost-effectiveness, and patient adherence.<\/jats:p>","DOI":"10.3390\/ph19060826","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T15:05:08Z","timestamp":1779721508000},"page":"826","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dose-Sparing Topical Administration: FK506-Loaded Nano-Micelles Achieve Efficient Therapy in a Murine Model of Vernal Keratoconjunctivitis"],"prefix":"10.3390","volume":"19","author":[{"given":"Zhen","family":"Liang","sequence":"first","affiliation":[{"name":"Henan Eye Hospital, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou 450003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Lu","sequence":"additional","affiliation":[{"name":"Henan Eye Hospital, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou 450003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Tao","sequence":"additional","affiliation":[{"name":"Henan Eye Hospital, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou 450003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Henan Eye Hospital, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou 450003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Song","sequence":"additional","affiliation":[{"name":"Henan Eye Hospital, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou 450003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyun","family":"Xia","sequence":"additional","affiliation":[{"name":"Henan Eye Hospital, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou 450003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jijun","family":"He","sequence":"additional","affiliation":[{"name":"Henan Eye Hospital, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou 450003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaping","family":"Yao","sequence":"additional","affiliation":[{"name":"Henan Eye Hospital, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou 450003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fudan","family":"Dong","sequence":"additional","affiliation":[{"name":"Henan Eye Hospital, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou 450003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Henan Eye Hospital, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou 450003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guojuan","family":"Pu","sequence":"additional","affiliation":[{"name":"Henan Eye Hospital, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou 450003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Henan Eye Hospital, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou 450003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s12016-023-08970-4","article-title":"Vernal Keratoconjunctivitis: A Systematic Review","volume":"65","author":"Bruschi","year":"2023","journal-title":"Clin. 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