Nanovesicular Drug Delivery Systems for Rare Ocular Diseases: Advances, Challenges, and Future Directions.

The present work focuses on investigating the potential of nanovesicular drug and gene delivery systems in addressing therapeutic challenges associated with rare ocular diseases, including Leber's congenital amaurosis, retinitis pigmentosa, and Stargardt disease. These inherited retinal disorders are characterized by a genetic origin, progressive vision loss, and a lack of effective treatment options. Traditional drug delivery methods are limited by multiple ocular barriers such as the corneal epithelium, blood-aqueous barrier, and blood-retinal barrier, which significantly restrict drug penetration and therapeutic efficacy. Nanovesicular systems, including liposomes, niosomes, ethosomes, exosomes, and ultradeformable vesicles, have emerged as promising strategies to overcome these challenges by enhancing drug stability, enabling controlled release, and improving targeted delivery to ocular tissues. These self-assembled nanoscale carriers offer sustained drug release, prolonged ocular retention, and reduced systemic side effects, making them highly suitable for treating rare ocular disorders. Advances in surface functionalization, ligand-based targeting, and hybrid nanocarrier development have further optimized their therapeutic potential. Additionally, exosome-based and lipid nanoparticle-mediated gene delivery systems have demonstrated the ability to transport nucleic acids, including plasmid DNA, siRNA, and CRISPR components, for precise genetic modulation in inherited retinal diseases. Despite their potential, clinical translation remains challenging due to issues such as stability, large-scale manufacturing, and regulatory hurdles. Future research should focus on optimizing formulation strategies, improving ocular penetration, and addressing long-term safety concerns to advance nanovesicular platforms from preclinical studies to clinical applications. By overcoming these challenges, nanovesicular drug and gene delivery systems hold great promise in revolutionizing treatments for rare ocular diseases, offering more effective, targeted, and minimally invasive therapeutic solutions for patients with currently limited options.