Multifunctional Hydrogel Eye Drops for Synergistic Treatment of Ocular Inflammatory Disease

  • ACS Nano. 2023 Oct 27. doi: 10.1021/acsnano.3c08869.
Xinyu Liu  1 Zhongxing Chen  1 Jieyi Bai  2 Xin Li  1 Xin Chen  1 Zheng Li  1 Hongxian Pan  1 Siheng Li  3 Qingyi Gao  1 Nan Zhao  4 Aodong Chen  1 Huilin Xu  3 Yinuo Wen  1 Lan Du  3 Mei Yang  1 Xingtao Zhou  1 Jinhai Huang  1
Affiliations
  • 1. Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University; Key Laboratory of Myopia, Chinese Academy of Medical Sciences; Shanghai Research Center of Ophthalmology and Optometry, Shanghai 200030, China.
  • 2. Department of Ophthalmology, Ordos Central Hospital, Ordos, Inner Mongolia 017000, P.R. China.
  • 3. School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
  • 4. School of Chemical Engineering, Northeast Electric Power University, Jilin 132000, P. R. China.
Abstract

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-α, 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.

Keywords
hydrogel eye drops; metal−organic frameworks; noninvasive drug delivery; reactive oxygen species; synergistic treatment; uveitis.
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