Corneal stromal fibrosis is a common cause of visual impairment resulting from corneal injury, inflammation and surgery. Therefore, there is an unmet need for inhibiting corneal stromal fibrosis. However, bioavailability of topical eye drops is very low due to the tear and corneal barriers. delivery offers a unique alternative to improve efficacy and minimize systemic toxicity. Herein, a drug delivery platform based on thermoresponsive injectable hydrogel/nano-micelles composite with drug-controlled release and long-acting features is developed to prevent corneal scarring and reduce corneal stromal fibrosis in lamellar keratoplasty. The gelation hydrogels enabled direct delivery of celastrol to the corneal stroma. evaluation with a rabbit anterior lamellar keratoplasty model showed that hydrogel/micelles platform could effectively inhibit corneal stromal fibrosis. This strategy achieves controlled and prolonged release of celastrol in the corneal stroma of rabbit. Following a single corneal interlamellar injection, celastrol effectively alleviated fibrosis mTORC1 signal promoting autophagy and inhibiting TGF-β1/Smad2/3 signaling pathway. Overall, this strategy demonstrates promise for the clinical application of celastrol in preventing corneal scarring and reducing corneal stromal fibrosis post-lamellar keratoplasty, highlighting the potential benefits of targeted drug delivery systems in ocular therapeutics.

中文翻译：

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用于板层角膜移植术的可注射热敏水凝胶：原位释放雷公藤红醇并抑制角膜疤痕


角膜基质纤维化是角膜损伤、炎症和手术导致视力障碍的常见原因。因此，抑制角膜基质纤维化的需求尚未得到满足。然而，由于泪液和角膜屏障，局部滴眼液的生物利用度非常低。给药提供了一种独特的替代方案，可以提高疗效并最大限度地减少全身毒性。在此，开发了一种基于热响应性可注射水凝胶/纳米胶束复合材料的药物递送平台，具有药物控制释放和长效特性，以防止板层角膜移植术中角膜疤痕形成并减少角膜基质纤维化。凝胶化水凝胶能够将雷公藤红素直接递送至角膜基质。兔前板层角膜移植模型评价表明，水凝胶/胶束平台可以有效抑制角膜基质纤维化。该策略实现了雷公藤红醇在兔角膜基质中的受控和延长释放。单次角膜层间注射后，雷公藤红醇可有效减轻纤维化 mTORC1 信号，促进自噬并抑制 TGF-β1/Smad2/3 信号通路。总体而言，该策略展示了雷公藤红醇在预防角膜疤痕和减少板层角膜移植术后角膜基质纤维化方面的临床应用前景，突出了靶向药物输送系统在眼部治疗中的潜在益处。