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A major therapeutic challenge is maintaining effective drug concentrations, as topical formulations are rapidly cleared by blinking and tear turnover. To address this limitation, we developed a dual pH\u2010 and temperature\u2010responsive composite hydrogel composed of chitosan (Cs)\u2010grafted poly\u2010N\u2010isopropylacrylamide (PNIPAAm)\u2010 CPN integrated with alginate\u2010based insulin\u2010imprinted microgels (IMIP). Incorporation of IMIP particles allowed tuning of rheology, swelling behavior, wettability, and biodegradation while preserving proper topical administration. Microgel addition increased viscosity from 3.1 mPa\u00b7s (CPN\u2010IMIP10) to 37.3 mPa\u00b7s (CPN\u2010IMIP35), and the sol\u2013gel transition between 25 and 37\u00b0C enabled flowability at room temperature followed by rapid gelation on the ocular surface. All CPN\u2010IMIP hydrogels exhibited elastic\u2010dominant behavior (G\u2032 &gt; G\u2033), confirming formation of a stable, shear\u2010resistant network. Insulin release was tunable: at pH 6.4 and 25\u00b0C, diffusion governed delivery (29.8 \u00b1 3.6% at 48\u00a0h), whereas at pH 7.4 and 37\u00b0C, swelling\u2010controlled release predominated (54.4 \u00b1 4.8%). The composite hydrogels supported human corneal epithelial cell viability and enhanced tear secretion, preserved corneal integrity, and reduced inflammation in a rat DES model. This system provides a minimally invasive, long\u2010acting therapeutic platform for DES.<\/jats:p>","DOI":"10.1002\/mabi.202600003","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T18:06:11Z","timestamp":1781805971000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual\u2010Responsive Chitosan\u2010Grafted PNIPAAm Hydrogel Eye Drop Incorporating Insulin\u2010Imprinted Microgels for Dry Eye Syndrome Treatment"],"prefix":"10.1002","volume":"26","author":[{"given":"Masoumeh Alsadat","family":"Hosseini","sequence":"first","affiliation":[{"name":"Department of Materials Engineering Isfahan University of Technology  Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reihaneh","family":"Khademi","sequence":"additional","affiliation":[{"name":"Department of Materials Engineering Isfahan University of Technology  Isfahan 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