Multifunctional Hydrogel Eye Drops for Synergistic Treatment of Ocular Inflammatory Disease.

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 (<i>e.g.</i>, 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.