Light-Triggered and Sustained Delivery of Dexamethasone Using Chitosan-Coated PLGA Nanoparticles for Posterior Eye...

Degenerative eye disorders (DEDs) such as age-related macular degeneration and diabetic retinopathy pose significant therapeutic challenges due to anatomical barriers limiting drug access to posterior ocular tissues. Current treatments, including intravitreal injections, offer localized delivery but require repeated administration, increasing risks and reducing patient compliance. This study introduces a dual-functional nanoparticulate platform for sustained and light-triggered delivery of dexamethasone, a corticosteroid widely used in DED management. Poly-(lactic-co-glycolic acid) (PLGA) nanoparticles were fabricated via nanoprecipitation, coloaded with dexamethasone and the near-infrared (NIR)-responsive dye IR820, and coated with chitosan to enhance mucoadhesion. Physicochemical characterization confirmed nanoscale size, monodispersity, and positive surface charge upon chitosan coating. Drug release studies revealed biphasic kinetics, with chitosan-coated formulations exhibiting prolonged release compared to uncoated particles. Under irradiation (800 nm), photothermal activation mediated by a NIR-absorbing dye induced a 2.0-2.3-fold increase in dexamethasone release during early exposure phases, enabling on-demand dosing. Cyto- compatibility assays on NIH-3T3 fibroblasts confirmed high cell viability (>70%) across all formulations and exposure conditions. These findings demonstrate a robust, light-responsive, mucoadhesive nanoparticle system with the potential to improve therapeutic precision and reduce invasiveness in posterior eye disease treatment.