Journal
ACS NANO
Volume -, Issue -, Pages -Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.3c08869
Keywords
hydrogel eye drops; uveitis; synergistic treatment; noninvasive drug delivery; metal-organic frameworks; reactive oxygen species
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In this study, multifunctional hydrogel eye drops were developed for the synergistic treatment of uveitis. These eye drops offer improved ocular bioavailability and unexpected anti-inflammatory efficacy. By mitigating the ophthalmic inflammatory reaction and suppressing inflammatory cytokines, the eye drops demonstrated superior efficacy in treating endotoxin-induced uveitis.
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.
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