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<p>Oxidative stress plays a role in corneal epithelial disorders by inducing inflammation and apoptosis of corneal epithelial cells. Although the topical administration of conventional eye drops is the most commonly used treatment, their high dosing frequency may reduce patient adherence and therapeutic outcomes. In the study, we developed a nitric oxide (NO)-releasing hydrogel—GSNO-grafted carboxymethyl cellulose (CMC-GSNO)—as a sustained-release topical formulation for corneal wound healing. CMC-GSNO was synthesized by EDC/NHS crosslinking and nitrosation. The properties of CMC-GSNO synthesized using EDC/NHS activation for either 1 or 2&#xa0;h were characterized by FTIR, <sup>1</sup>H NMR, Ellman’s assay, Griess assay, DPPH assay, SEM and in vitro drug release analysis. Both 1&#xa0;h and 2&#xa0;h activation conditions produced porous hydrogels with sustained NO release over 7&#xa0;days, following first-order kinetics (R<sup>2</sup> &gt; 0.92). The optimized formulation (1% CMC-GSNO (1.24)), with an NO concentration of 159&#xa0;μM, showed no cytotoxicity in SIRC cells. In a post-treatment cellular model, 1% CMC-GSNO (1.24) was shown to reduce oxidative stress-induced damage in SIRC cells by downregulating inflammatory gene expression (<i>TNF</i>, <i>IL-1α</i>, <i>IL-6</i>, <i>IL-8</i>, <i>MMP-3</i>, and <i>MMP-9</i>), decreasing apoptosis, and enhancing cell viability. The ocular biocompatibility of 1% CMC-GSNO (1.24) was demonstrated in a rabbit model. These results suggest that CMC-GSNO is a promising NO-releasing hydrogel with sustained therapeutic activity and biocompatibility, offering potential as a topical ocular treatment for oxidative stress-related corneal disorders with reduced dosing frequency.</p>

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Development of S-nitrosoglutathione-grafted carboxymethyl cellulose for treating oxidative stress-related ocular surface diseases

  • 期刊论文

  • 发表日期：

    2025年12月1日

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  • Ching-Yao Tsai,
  • I-Lun Tsai,
  • Ya-Hsien Wang,
  • Yun-Jou Tseng,
  • Ruy-Yu Ku,
  • Yung-Hsin Cheng

摘要

Oxidative stress plays a role in corneal epithelial disorders by inducing inflammation and apoptosis of corneal epithelial cells. Although the topical administration of conventional eye drops is the most commonly used treatment, their high dosing frequency may reduce patient adherence and therapeutic outcomes. In the study, we developed a nitric oxide (NO)-releasing hydrogel—GSNO-grafted carboxymethyl cellulose (CMC-GSNO)—as a sustained-release topical formulation for corneal wound healing. CMC-GSNO was synthesized by EDC/NHS crosslinking and nitrosation. The properties of CMC-GSNO synthesized using EDC/NHS activation for either 1 or 2 h were characterized by FTIR, 1H NMR, Ellman’s assay, Griess assay, DPPH assay, SEM and in vitro drug release analysis. Both 1 h and 2 h activation conditions produced porous hydrogels with sustained NO release over 7 days, following first-order kinetics (R2 > 0.92). The optimized formulation (1% CMC-GSNO (1.24)), with an NO concentration of 159 μM, showed no cytotoxicity in SIRC cells. In a post-treatment cellular model, 1% CMC-GSNO (1.24) was shown to reduce oxidative stress-induced damage in SIRC cells by downregulating inflammatory gene expression (TNF, IL-1α, IL-6, IL-8, MMP-3, and MMP-9), decreasing apoptosis, and enhancing cell viability. The ocular biocompatibility of 1% CMC-GSNO (1.24) was demonstrated in a rabbit model. These results suggest that CMC-GSNO is a promising NO-releasing hydrogel with sustained therapeutic activity and biocompatibility, offering potential as a topical ocular treatment for oxidative stress-related corneal disorders with reduced dosing frequency.