Navigating the ocular barrier: Viral- and nanotechnology-based delivery systems as promising therapeutic agents for...

While the intricate and precisely specialized structure of the human eye is critical for its appropriate function, it also presents a number of anatomical and physiological barriers, such as tight junctions, enzymatic degradation, and dynamic fluid turnover, which highly restrict the intraocular bioavailability of various therapeutic compounds. This is more significant for those therapeutic compounds that are used for complications affecting the posterior segment. Accordingly, conventional therapeutic strategies for common ocular complications such as diabetic retinopathy (DR), age-related macular degeneration (AMD), glaucoma, and infectious keratitis significantly demand invasive administration approaches and multiple injections, frequently resulting in various side effects and suboptimal therapeutic consequences. To address these major challenges, novel technologies, such as viral- and nanotechnology-based delivery systems, have provided emerging opportunities to bypass ocular barriers and facilitate targeted, maintained, and efficient drug and gene delivery. The present review aims to comprehensively describe the current advancements in both viral- and nanotechnology-based strategies for ocular diseases. It discusses the complex molecular structure and physiological functions of the ocular barriers, focusing on the exact mechanisms that restrict drug permeation. Moreover, this review describes the design principles, physicochemical properties, and therapeutic potential of diverse viral- and nanotechnology-based delivery systems. Their efficacy and safety profiles are thoroughly discussed across various pre-clinical and clinical studies. Furthermore, the review discusses the emergence of hybrid viral-nanotechnology delivery systems that combine the strengths of both approaches, offering enhanced targeting precision and biocompatibility. The major challenges linked to the clinical translation of these novel technologies, such as aspects of biocompatibility and immunogenicity are also addressed. This review highlights the significant transformative potential of viral vectors and nanotechnology in reforming ocular disease management and increasing patient quality of life.