Nanogel biomaterials for ocular applications

Ocular drug delivery remains a significant challenge due to multiple anatomical and physiological barriers that limit drug penetration, retention, and bioavailability. Although various nanocarrier systems, including nanoparticles, liposomes, and hydrogels, have been developed to address these limitations, they often suffer from rapid precorneal clearance, insufficient tissue compatibility, and limited control over drug release. Nanogels are nanoscale crosslinked polymer networks that combine hydrogel-like hydration and biocompatibility with nanoparticle-like transport properties, enabling tunable drug loading, release, and stimuli-responsive behavior. Importantly, these capabilities are fundamentally governed by the internal network architecture of nanogels, where parameters such as crosslinking density, mesh size, and surface functionality directly regulate transport behavior and biological interactions in ocular environments. This review provides a comprehensive and critical analysis of nanogels for ocular applications by establishing a systematic structure-property-function-application framework, introduced here for the first time, which directly links nanogel design parameters to their functional roles in overcoming specific ocular barriers. Unlike previous reviews that primarily focus on material composition or formulation strategies, this work emphasizes a network-governed design paradigm, highlighting how intermolecular interactions and crosslinking mechanisms dictate nanogel performance across different ocular conditions. Furthermore, disease-specific applications are discussed, demonstrating how rational nanogel design can be tailored to address distinct pathological and anatomical challenges in dry eye disease, corneal injury, infections, and retinal disorders. Key translational challenges, including safety, stability, and scalability, are critically analyzed to define current limitations and future design directions.