Nanostructured drug delivery systems for posterior segment eye diseases: Strategies to defy ocular barriers

Abstract Posterior segment eye diseases (PSEDs) remain a leading cause of irreversible blindness, with the eye's dynamic and static barriers posing challenges to effective drug delivery through different administration routes. Currently, treatment options available for PSEDs are limited, with invasive intravitreal injection being the predominant choice. However, frequent injections carry a high risk of complications, and are associated with low patient compliance. The rapid advancement of nanomaterials has sparked intense interest in nanoconstructed drug delivery systems as potential solutions to overcome these bottlenecks. Experimental studies have demonstrated that diverse nanocarriers can accommodate different therapeutic agents and circumvent ocular barriers through multiple mechanisms, including prolonged drug residence, enhanced tissue permeability, to name a few. In addition, nanomaterial‐based delivery systems also offer advantages in improving posterior segment drug delivery efficiency and therapeutic practicality. In this review, the multiple ocular barriers and traditional administration routes are presented first. Then, we focus on the promise held by nanoplatforms for barrier penetration and summarize key mechanisms involved. Meanwhile, the review highlights the value of nanocarriers in achieving efficient drug delivery and treatment of PSEDs with illustrative examples and tables. Finally, current challenges and future prospects are also discussed here to encourage basic research and clinical transformation.