Multifunctional Hydrogel Eye Drops for Synergistic Treatment of Ocular Inflammatory Disease

ACS Nano. 2023 Dec 26;17(24):25377-25390. doi: 10.1021/acsnano.3c08869. Epub 2023 Oct 27.

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.

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Dexamethasone* / pharmacology
  • Dexamethasone* / therapeutic use
  • Humans
  • Hydrogels / therapeutic use
  • Inflammation / drug therapy
  • Ophthalmic Solutions / pharmacology
  • Ophthalmic Solutions / therapeutic use
  • Reactive Oxygen Species / therapeutic use
  • Uveitis* / drug therapy

Substances

  • Dexamethasone
  • Hydrogels
  • Reactive Oxygen Species
  • Ophthalmic Solutions
  • UCON 50-HB-5100
  • Anti-Inflammatory Agents