Multifunctional Hydrogel Eye Drops for Synergistic Treatment of Ocular Inflammatory Disease

被引:25
作者
Liu, Xinyu [1 ,2 ,3 ,4 ]
Chen, Zhongxing [1 ,2 ,3 ,4 ]
Bai, Jieyi [7 ]
Li, Xin [1 ,2 ,3 ,4 ]
Chen, Xin [1 ,2 ,3 ,4 ]
Li, Zheng [1 ,2 ,3 ,4 ]
Pan, Hongxian [1 ,2 ,3 ,4 ]
Li, Siheng [5 ,6 ]
Gao, Qingyi [1 ,2 ,3 ,4 ]
Zhao, Nan [8 ]
Chen, Aodong [1 ,2 ,3 ,4 ]
Xu, Huilin [5 ,6 ]
Wen, Yinuo [1 ,2 ,3 ,4 ]
Du, Lan [5 ,6 ]
Yang, Mei [1 ,2 ,3 ,4 ]
Zhou, Xingtao [1 ,2 ,3 ,4 ]
Huang, Jinhai [1 ,2 ,3 ,4 ]
机构
[1] Fudan Univ, Eye Inst, Shanghai 200030, Peoples R China
[2] Fudan Univ, Eye & ENT Hosp, Dept Ophthalmol, Shanghai 200030, Peoples R China
[3] Chinese Acad Med Sci, Key Lab Myopia, Shanghai 200030, Peoples R China
[4] Shanghai Res Ctr Ophthalmol & Optometry, Shanghai 200030, Peoples R China
[5] Wenzhou Med Univ, Sch Ophthalmol & Optometry, Wenzhou 325027, Zhejiang, Peoples R China
[6] Wenzhou Med Univ, Eye Hosp, Wenzhou 325027, Zhejiang, Peoples R China
[7] Ordos Cent Hosp, Dept Ophthalmol, Ordos 017000, Inner Mongolia, Peoples R China
[8] Northeast Elect Power Univ, Sch Chem Engn, Jilin 132000, Peoples R China
基金
中国国家自然科学基金;
关键词
hydrogel eye drops; uveitis; synergistic treatment; noninvasive drug delivery; metal-organic frameworks; reactive oxygen species; UVEITIS; ADALIMUMAB;
D O I
10.1021/acsnano.3c08869
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Uveitis is a complex ocular inflammatory disease with a multifactorial etiology that can result in blindness. Although corticosteroid eye drops are the primary treatment for anterior uveitis, their efficacy is limited by low bioavailability, adverse effects, and a narrow focus on inflammation. In this study, the multifunctional hydrogel eye drops (designated as DCFH) were developed by incorporating the anti-inflammatory agent dexamethasone (DSP) and reactive oxygen species (ROS) scavenger cerium-based metal-organic frameworks (Ce-MOFs) into thermosensitive triblock copolymer F127 for the synergistic treatment against uveitis. The resulting F127 eye drops offer a favorable alternative to ophthalmic solution due to its thermosensitivity, thixotropy, light transmittance, improved ocular bioavailability, and unexpected anti-inflammatory efficacy. Notably, the participation of nanoporous Ce-MOFs, functional drug carriers, not only reduces ROS level but also boosts the anti-inflammatory activity of DSP in vitro. Therapeutically, the multifunctional DCFH exhibits superior efficacy in treating endotoxin-induced uveitis by mitigating the ophthalmic inflammatory reaction, suppressing inflammatory cytokines (e.g., TNF-alpha, IL-6, and IL-17) and downregulating the expression of iNOS and NLPR3. This synergistic treatment provides a valuable and promising approach for the management of uveitis and other ocular inflammatory conditions.
引用
收藏
页码:25377 / 25390
页数:14
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