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We developed nanomicelles (RH40\u2010P188\/RH40\u2010P407, CycloNex) for enhanced cyclosporine A (CsA) delivery through innovative biological validation platforms. The 15\u2010nm micelles demonstrated exceptional stability (3 months at 25\u00b0C) and deep tissue penetration (50\u00a0\u00b5m in 3D corneal spheroids), outperforming Cequa by 2.3\u2010fold in ex vivo rabbit corneal accumulation. A breakthrough microfluidic\u2010integrated 3D total corneal model revealed 82% prolonged ocular retention vs. Cequa, while our hyperosmotic cell platform showed 55% greater reactive oxygen species reduction and 44% lower TNF\u2010\u03b1 expression. In vivo studies confirmed NM\n                    <jats:sub>P188<\/jats:sub>\n                    \u2010CsA's superior bioavailability, and corneal repair was completed within 14 days in mice with benzalkonium chloride\u2010induced dry eye. These findings, validated through six complementary biological models\u2014including HET\u2010CAM irritation scoring (0.89\u00a0vs. Cequa's 1.34)\u2014establish a new paradigm for ocular nanotherapeutic evaluation while demonstrating clinically translatable advantages over current standards.\n                  <\/jats:p>","DOI":"10.1002\/smll.74981","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T06:50:50Z","timestamp":1785739850000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biomimetic Multimodal Evaluation Reveals Enhanced Efficacy and Safety of Cyclosporine A Nanomicelles (CycloNex) for Advanced Dry Eye Management"],"prefix":"10.1002","author":[{"given":"Xing","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics School of Pharmaceutical Sciences Hebei Medical University  Shijiazhuang People's Republic of 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