Stimuli‐responsive systems: A focus on controlled drug delivery for posterior segment ocular disease

Abstract Posterior segment ocular diseases pose substantial concerns as they can cause irreversible visual impairments. Effective management of these conditions necessitates the precise delivery of sufficient drug to the affected site. Current therapeutic approaches for chronic posterior segment disorders involve frequent intravitreal injections of drug solutions. However, the delivered agents have limited tissue penetration and poor bioavailability owing to the ocular physiological barriers. Traditional nano‐based drug delivery systems release drugs at a predetermined rate, lacking adaptability to modify release dynamics. Conversely, stimuli‐responsive nano‐based drug delivery systems have garnered considerable research attention, as they offer spatiotemporal control over drug release and possess the ability to adapt to pathological conditions. This intelligent nano‐based drug delivery system paves the path for personalized therapies of ocular diseases. This review encapsulates recent advancements in stimuli‐responsive nano‐based drug delivery systems, emphasizing their mechanisms and potential for treating posterior segment diseases. Additionally, we introduce recent developments in mechanically interlocked molecules and bioorthogonal reactions, which may usher in a new epoch in ocular drug delivery. The challenges and future perspectives of these tunable release systems are also discussed. Future refinements of these findings would enrich therapeutic strategies for posterior segment diseases, and bridge the gap between basic researches and clinical applications.