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<p>The unique physiological barriers and rapid clearance of the ocular surface result in less than 5% bioavailability of topical drugs, forcing frequent high-dose administration, reducing compliance, and risking toxicity. Existing ophthalmic semi-solid formulations can delay clearance but often cause blurred vision and foreign body sensation due to high viscosity, limiting clinical use. In this study, a polysaccharide-based dual-dynamic crosslinked hydrogel (HC gels) was prepared <i>via</i> an <i>in situ</i> Schiff base reaction between aldehyde-functionalized hyaluronic acid and aminated carboxymethylcellulose under physiological conditions for sustained ocular drug delivery. By modulating the gelation kinetics, a controllable transition from a low-viscosity solution to a gel (15–384 s) was achieved. The <i>in situ</i>-formed gel dynamically adapts to the ocular surface during blinking, forming a thin, uniform, transparent layer that ensures conformal coverage, resists blinking and tear clearance, and significantly extends drug retention. In a rat model of uveitis, HC gels effectively alleviated inflammation <i>via</i> sustained dexamethasone release. Overall, HC gels provide a novel strategy for safe, effective, and sustained ocular drug delivery.</p>

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Polysaccharide-based Hydrogel Formed via In situ Schiff Base Reaction with Contact Lens-like Ocular Surface Coverage for Sustained Ophthalmic Drug Delivery

  • 期刊论文

  • 发表日期：

    2026年5月26日

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  • Xin Yang,
  • Hai-Hua Wang,
  • Chao-Jun Yue,
  • De-Hua Tan,
  • Ge Sun,
  • Shuai-Jun Guo,
  • Hai-Liang Pei,
  • Yu-Lin Hu,
  • Shan-Hao Feng,
  • Yang Qiao,
  • Yi-Ming Hua,
  • Li-Juan Zhang,
  • Shi-Lei Zhu,
  • Ya-Nan Ye,
  • Qiang Zheng

摘要

The unique physiological barriers and rapid clearance of the ocular surface result in less than 5% bioavailability of topical drugs, forcing frequent high-dose administration, reducing compliance, and risking toxicity. Existing ophthalmic semi-solid formulations can delay clearance but often cause blurred vision and foreign body sensation due to high viscosity, limiting clinical use. In this study, a polysaccharide-based dual-dynamic crosslinked hydrogel (HC gels) was prepared via an in situ Schiff base reaction between aldehyde-functionalized hyaluronic acid and aminated carboxymethylcellulose under physiological conditions for sustained ocular drug delivery. By modulating the gelation kinetics, a controllable transition from a low-viscosity solution to a gel (15–384 s) was achieved. The in situ-formed gel dynamically adapts to the ocular surface during blinking, forming a thin, uniform, transparent layer that ensures conformal coverage, resists blinking and tear clearance, and significantly extends drug retention. In a rat model of uveitis, HC gels effectively alleviated inflammation via sustained dexamethasone release. Overall, HC gels provide a novel strategy for safe, effective, and sustained ocular drug delivery.