ADVANCES IN POLYPHENOL-BASED OCULAR DRUG DELIVERY: MECHANISTIC INSIGHTS, FORMULATION INNOVATIONS, AND TRANSLATIONAL PERSPECTIVES

Polyphenols, a structurally diverse class of plant-derived phytoconstituents, possess potent antioxidant, anti-inflammatory, and vasoprotective properties that make them promising therapeutic candidates for ocular disorders driven by oxidative stress, chronic inflammation, and overall health. Despite this potential, their clinical translation remains restricted due to the inherent limitations of conventional ocular delivery systems, such as low ocular bioavailability, rapid precorneal elimination, poor corneal permeability, and inadequate targeting of posterior ocular tissues. To address these challenges, recent research has focused on advanced formulation approaches designed to enhance polyphenol retention, penetration, and sustained release within ocular tissues. These include nanoemulsions, polymeric micelles lipid and polymer-based nanocarriers, in situ gelling systems, mucoadhesive and stimuli-responsive platforms, and advanced drug delivery platforms for the posterior and anterior ocular segments. Mechanistically, these systems exploit physicochemical and biological strategies such as enhancing mucoadhesion, modulating paracellular transport, and leveraging endocytic uptake to improve drug disposition and therapeutic performance. The review critically examines these innovative formulation platforms, delineates their pharmacokinetic and pharmacodynamic outcomes, and discusses safety, manufacturing challenges, and regulatory considerations that presently influence their clinical progression. Overall, it highlights emerging formulation technologies most likely to facilitate the successful clinical translation of polyphenol-based ocular therapies.