Reactive Oxygen Species-Responsive Dual Anti-Inflammatory and Antioxidative Nanoparticles for Anterior Uveitis.

ABSTRACT

Anterior uveitis (AU) is an immune-mediated inflammatory disease that results in iritis, cyclitis, glaucoma, cataracts, and even a loss of vision. The frequent and long-term administration of corticosteroid drugs is limited in the clinic owing to the side effects and patient noncompliance with the drugs. Therefore, specifically delivering drugs to inflammatory anterior segment tissues and reducing the topical application dosage of the drug are still a challenge. Here, we developed dual dexamethasone (Dex) and curcumin (Cur)-loaded reactive oxygen species (ROS)-responsive nanoparticles (CPDC NPs) to treat anterior uveitis. The CPDC NPs demonstrated both anti-inflammatory and antioxidative effects, owing to their therapeutic characteristics of dexamethasone and curcumin, respectively. The CPDC NPs could effectively release dexamethasone and curcumin in the oxidizing physiological environment of the inflammation tissue. The CPDC NPs can effectively internalize by activated macrophage cells, subsequently suppressing the proinflammatory factor expression. Moreover, the CPDC NPs can inhibit ROS and inflammation via nuclear transcription factor E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway activation. In an endotoxin-induced uveitis rabbit model, the CPDC NPs show a therapeutic effect that is better than that of either free drugs or commercial eye drops. Importantly, the CPDC NPs with a lower dexamethasone dosage could reduce the side effects significantly. Taken together, we believe that the dual-drug-loaded ROS-responsive NPs could effectively target and inhibit inflammation and have the potential for anterior uveitis treatment in clinical practice.