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一种用于结膜下损伤的可注射形状自适应水凝胶系统:并持续释放雷帕霉素以预防纤维化并促进自噬。

An injectable shape-adaptive hydrogel system for subconjunctival injuries: and permanently releases rapamycin to prevent fibrosis promoting autophagy.

作者信息

Sun Xue, Cui Haohao, Li Jingfan, An Boyuan, Liu Ruixing, Guo Zhihua, Chu Dandan, Geng Xingchen, Cui Bingbing, Zhu Lei, Li Jingguo, Li Zhanrong

机构信息

Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, China.

出版信息

Mater Today Bio. 2024 Dec 10;30:101380. doi: 10.1016/j.mtbio.2024.101380. eCollection 2025 Feb.

Abstract

Subconjunctival fibrosis (SCF) is a common and refractory eye disease that is a serious threat to vision. The severe side effects of existing drugs and low drug bioavailability due to the ocular barrier are major challenges in SCF treatment. Hence, there is an urgent need to explore safer and more effective strategies for administering anti-SCF drugs. Herein, an injectable and adaptable hydrogel system containing the antifibrotic drug rapamycin was fabricated to address this complex need. This system possesses moderate mechanical properties, self-healing and shape-adaptive capabilities, injectability, and biosafety. It is designed to promote autophagy by modulating the PI3K/AKT/mTOR/WIPI2 pathway, thereby inhibiting SCF. experiments utilizing a rat subconjunctival injury model indicated that administration of this hydrogel system effectively inhibited SCF. This system constitutes a promising method for promoting autophagy to protect against SCF, which will foster its widespread application for other fibrotic diseases.

摘要

结膜下纤维化(SCF)是一种常见且难治的眼病,对视力构成严重威胁。现有药物的严重副作用以及由于眼部屏障导致的低药物生物利用度是SCF治疗中的主要挑战。因此,迫切需要探索更安全、更有效的抗SCF药物给药策略。在此,制备了一种含有抗纤维化药物雷帕霉素的可注射且适应性强的水凝胶系统,以满足这一复杂需求。该系统具有适度的机械性能、自愈和形状适应能力、可注射性和生物安全性。它旨在通过调节PI3K/AKT/mTOR/WIPI2途径促进自噬,从而抑制SCF。利用大鼠结膜下损伤模型进行的实验表明,给予该水凝胶系统可有效抑制SCF。该系统构成了一种有前景的促进自噬以预防SCF的方法,这将促进其在其他纤维化疾病中的广泛应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53ac/11713510/96645a3902b4/ga1.jpg

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