**Background:** Ocular diseases profoundly impact vision and quality of life, with over 2.2 billion people worldwide experiencing vision impairment according to the WHO. The human eye is protected by multiple anatomical and physiological barriers that hinder drug delivery. The anterior segment includes the cornea, conjunctiva, iris, ciliary body, and lens; the posterior segment includes the vitreous humor, retina, choroid, sclera, and optic nerve. Conventional drug administration routes—topical, systemic, intraocular, and periocular—face limitations such as low bioavailability (typically 0.1% to 5% for topical delivery), rapid clearance, and poor patient compliance. Nanotechnology-based drug delivery systems have emerged as a promising solution to overcome these barriers and improve therapeutic outcomes.
**Methods:** This is a narrative review that synthesizes the current literature on nano-based ocular drug delivery systems. The authors describe the anatomy and barriers of the eye, conventional routes of administration, and various nanocarrier types. They discuss nanomicelles, nanoparticles (including solid lipid nanoparticles and nanostructured lipid carriers), nanosuspensions, nanoemulsions, microemulsions, nanofibers, dendrimers, liposomes, niosomes, nanowafers, contact lenses, hydrogels, microneedles, and gene therapy approaches. The review also covers controlled drug delivery systems, including light-activated and stimuli-responsive systems. The authors provide examples of FDA-approved products and recent exploratory studies, summarizing key findings from in vitro and in vivo research.
**Key Results:** The review highlights the characteristics and clinical applications of each nanocarrier type. Nanomicelles (5–100 nm) improve solubility and targeted delivery; the FDA-approved Cequa® (0.09% cyclosporine A nanomicellar solution) shows better efficacy than oil-based vehicles. Nanoparticles (1–1000 nm, with 50–400 nm preferred for ocular delivery) include polymeric and lipid-based types; PLGA nanoparticles loaded with bevacizumab sustained vitreous concentrations above 500 ng/mL for over 8 weeks in rabbits. Nanosuspensions (<1 μm, typically 200–500 nm) enhance the delivery of poorly soluble drugs. Nanoemulsions (20–500 nm) extend pre-corneal retention and increase bioavailability; cationic nanoemulsions interact with the anionic corneal mucin layer. Nanofibers (tens to hundreds of nanometers) offer high drug loading and extended release; for example, dexamethasone-loaded PCL nanofibers provided controlled release for 10 days. Dendrimers (e.g., PAMAM) can be functionalized; DenTimol reduced IOP by 7.3 mmHg (30% from baseline) in rats. Liposomes (0.025–10 μm) and niosomes are used for dry eye, fungal keratitis, and glaucoma; azithromycin liposomes showed 2-fold greater corneal permeation than solution. Nanowafers (e.g., PVA-based) provide sustained release; a cysteamine nanowafer administered once daily was twice as effective as twice-daily eye drops in cystinosis mice. Contact lenses incorporating nanoparticles can achieve over 50% ocular bioavailability; micelles-laden contact lenses showed 9.8 times higher relative pharmacological availability compared to eye drops. Hydrogels (natural and synthetic) offer biocompatibility and adjustable drug release. Microneedles (<1 mm) allow minimally invasive delivery; dissolving microneedles for fluconazole increased drug residence time by 2.5 h. Gene therapy using nonviral (e.g., lipid nanoparticles, carbon dots) and viral vectors (e.g., AAV) is advancing for retinal diseases. The review also notes that light-activated systems, particularly near-infrared (700–900 nm), enable precise spatiotemporal drug release. Toxicity concerns remain, with inconsistent results across in vitro and in vivo models.
**Clinical Implications:** Nanocarrier-based systems have the potential to significantly improve ocular drug delivery by enhancing drug permeability, stability, and targeted release, thereby improving bioavailability and reducing dosing frequency. Several FDA-approved products (e.g., Cequa®, Visudyne®, Dextenza®, Restasis®) are already in clinical use for conditions such as dry eye disease, age-related macular degeneration, and ocular inflammation. However, challenges persist, including potential nanomaterial toxicity, scale-up difficulties, and the need for noninvasive delivery to the posterior segment. Thorough evaluation of safety, therapeutic requirements, market demand, and regulatory aspects is essential for clinical translation. Continued innovation in nanocarrier design and delivery strategies is needed to address these limitations and expand treatment options for ocular diseases.