Recent advances and future challenges in nanosystems for ocular drug delivery.

Ocular drug delivery faces significant challenges because of the eye's complexity and anatomical barriers, such as the cornea, conjunctiva, and blood-retinal barrier, which limit drug penetration and bioavailability. Recent advances in nanotechnology-based drug delivery have led to the development of innovative delivery platforms, enabling targeted, sustained, and minimally invasive delivery for ocular diseases and injuries. This review outlines the recent advances in nanosystems-based ocular drug delivery and highlights the latest progress in targeting technologies based mainly on preclinical studies and selected clinical trial data. It covers a variety of nanosystems, including organic nanoparticles (NPs) such as liposomes, nanomicelles, nanosuspensions, nanoemulsions, dendrimers, and nanofibers. Additionally, it addresses inorganic NPs, which include gold NPs, silver NPs, silica NPs, and carbon nanotubes. Besides, we summarize the clinical challenges and regulatory aspects in nanotechnology-based ocular drug delivery. Finally, inspired by current advances and therapeutic strategies, we provide an insight into clinical applications and future research directions on nanosystems-based drug delivery. We highlight the need to overcome the challenges of using nanosystems in ocular drug delivery and fill the knowledge gap on their nanotoxicity and future development. SIGNIFICANCE STATEMENT: This review highlights recent advances in nanosystem applications for ocular drug delivery, summarizes up-to-date clinical trials utilizing nanosystems for ocular drug delivery, and discusses clinical challenges and directions for future development.