Scholarlink

<p>Diabetic retinopathy affects over 30% of diabetic patients globally, with current treatments remaining invasive and painful. While quercetin demonstrates potent antioxidant properties, its therapeutic potential is limited by poor ocular bioavailability and lack of optimized delivery systems for topical administration. We systematically developed and compared quercetin-loaded nanoparticulate suspension versus thermosensitive in-situ gel formulations using Quality-by-Design principles to identify the superior delivery platform for diabetic retinopathy treatment. We optimized formulations through multilevel categorical design, evaluating three polymers (HPMC, EC, CMC) and three sonication times (20–40&#xa0;min). Both optimized formulations underwent comprehensive characterization and direct head-to-head comparison in streptozotocin-induced diabetic rats (50&#xa0;mg/kg, 15 weeks, 5 µL/eye three times daily). QbD optimization yielded HPMC-based nanoparticles measuring 336.9&#xa0;nm (PDI 0.465) with + 17.31 mV zeta potential and 81.16% sustained release over 400&#xa0;min. The thermosensitive in-situ gel demonstrated rapid gelation at physiological temperature (35–38&#xa0;°C) and significantly prolonged drug release (18&#xa0;h) compared to suspension (6.7&#xa0;h). In diabetic rats, the in-situ gel consistently outperformed suspension across all therapeutic endpoints: retinal inner nuclear layer thickness preserved at 36.47 ± 2.54&#xa0;μm versus 24.34 ± 2.46&#xa0;μm with suspension (<i>p</i> &lt; 0.001, representing 50% better preservation). The gel achieved superior anti-inflammatory effects (TNF-α reduced by 56% versus 37% with suspension, <i>p</i> &lt; 0.001; IL-6 reduced by 48% versus 34%, <i>p</i> &lt; 0.001) and greater antioxidant restoration (catalase: 36.47 ± 2.54 versus 24.34 ± 2.46 µmol/min/mg, <i>p</i> &lt; 0.05). Therapeutic benefits occurred independently of glycemic control, confirming direct retinal protection.This comparative study demonstrates that thermosensitive in-situ gel technology provides 21–50% superior therapeutic outcomes over conventional nanoparticulate suspension for quercetin delivery in diabetic retinopathy. The gel’s enhanced performance, achieved through prolonged ocular residence and sustained drug delivery, establishes it as the preferred formulation for advancing quercetin-based therapy toward clinical application in diabetic retinopathy management.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

QbD-Optimized QuercetinNanoparticulate Ophthalmic Systems for Diabetic Retinopathy: Suspension Versus In-Situ Gel

  • 期刊论文

  • 发表日期：

    2026年5月13日

查看全文
  • Geetanjali Sahu,
  • Swarnali Das Paul

摘要

Diabetic retinopathy affects over 30% of diabetic patients globally, with current treatments remaining invasive and painful. While quercetin demonstrates potent antioxidant properties, its therapeutic potential is limited by poor ocular bioavailability and lack of optimized delivery systems for topical administration. We systematically developed and compared quercetin-loaded nanoparticulate suspension versus thermosensitive in-situ gel formulations using Quality-by-Design principles to identify the superior delivery platform for diabetic retinopathy treatment. We optimized formulations through multilevel categorical design, evaluating three polymers (HPMC, EC, CMC) and three sonication times (20–40 min). Both optimized formulations underwent comprehensive characterization and direct head-to-head comparison in streptozotocin-induced diabetic rats (50 mg/kg, 15 weeks, 5 µL/eye three times daily). QbD optimization yielded HPMC-based nanoparticles measuring 336.9 nm (PDI 0.465) with + 17.31 mV zeta potential and 81.16% sustained release over 400 min. The thermosensitive in-situ gel demonstrated rapid gelation at physiological temperature (35–38 °C) and significantly prolonged drug release (18 h) compared to suspension (6.7 h). In diabetic rats, the in-situ gel consistently outperformed suspension across all therapeutic endpoints: retinal inner nuclear layer thickness preserved at 36.47 ± 2.54 μm versus 24.34 ± 2.46 μm with suspension (p < 0.001, representing 50% better preservation). The gel achieved superior anti-inflammatory effects (TNF-α reduced by 56% versus 37% with suspension, p < 0.001; IL-6 reduced by 48% versus 34%, p < 0.001) and greater antioxidant restoration (catalase: 36.47 ± 2.54 versus 24.34 ± 2.46 µmol/min/mg, p < 0.05). Therapeutic benefits occurred independently of glycemic control, confirming direct retinal protection.This comparative study demonstrates that thermosensitive in-situ gel technology provides 21–50% superior therapeutic outcomes over conventional nanoparticulate suspension for quercetin delivery in diabetic retinopathy. The gel’s enhanced performance, achieved through prolonged ocular residence and sustained drug delivery, establishes it as the preferred formulation for advancing quercetin-based therapy toward clinical application in diabetic retinopathy management.