**Background:** The eye's unique anatomy and physiology present significant barriers to effective drug delivery, especially for chronic diseases affecting the posterior segment (e.g., age-related macular degeneration, diabetic retinopathy). Conventional topical eye drops achieve less than 5% bioavailability due to tear turnover, corneal impermeability, and the blood–retinal barrier. Systemic administration delivers only 1%–2% of the drug to the retina, while intravitreal injections, though effective, are invasive and associated with complications like hemorrhage, retinal detachment, and endophthalmitis. There is a critical need for noninvasive, sustained, and targeted delivery systems.
**Methods:** This is a narrative review of the current literature on ocular barriers, routes of administration, and nanocarrier-based drug delivery systems. The authors describe the anatomy of the eye (anterior segment: cornea, conjunctiva, anterior/posterior chambers; posterior segment: sclera, choroid, retina, vitreous humor) and the specific barriers each presents. They then review various nanocarrier platforms—including nanosuspensions, nanoemulsions, polymeric nanomicelles, solid lipid nanoparticles, liposomes, niosomes, dendrimers, and nanowafers—and discuss their benefits and limitations. The review also summarizes recent clinical trials and patents on nanocarrier-based ocular therapies.
**Key Results:** The paper does not present original experimental data but synthesizes findings from the literature. Key points include:
- Tear turnover rate is 1.2 μl/min (basal) and can increase 100-fold with reflex stimulation.
- Only about 5% of a topically applied drug is absorbed through the ocular surface.
- Intravitreal injections of anti-VEGF agents (e.g., bevacizumab, ranibizumab, brolucizumab) are highly successful for AMD but require frequent administration and carry risks.
- Nanocarriers (size 10–1000 nm) can improve drug retention and penetration. Cationic nanocarriers are attracted to the negatively charged cornea and conjunctiva, enhancing topical delivery to the anterior segment. Anionic nanocarriers diffuse better in the vitreous and can reach the retina.
- Examples of marketed nanocarrier-based products include TobraDex® ST (xanthan gum), Timoptic-XE® (gellan gum), ILEVRO® (guar gum), DUREZOL® (difluprednate emulsion), and Verisome® (biodegradable gel for triamcinolone acetonide).
- Clinical trials are ongoing for nanocarrier formulations of dexamethasone, sirolimus, cyclosporine, nepafenac, and others for conditions like dry eye, uveitis, diabetic macular edema, and postoperative inflammation.
**Clinical Implications:** Nanocarrier-based drug delivery systems offer a promising solution to the limitations of conventional ocular therapies. By enhancing drug solubility, prolonging retention time, and enabling targeted delivery, these systems can reduce dosing frequency, improve patient compliance, and minimize systemic side effects. For posterior segment diseases, nanocarriers may eventually provide a noninvasive alternative to intravitreal injections. However, challenges remain, including scalability, cytotoxicity, and the need for biocompatible materials that can release drugs in a controlled manner over months. Future research should focus on smart delivery systems responsive to stimuli (e.g., light) and on understanding the pathophysiology of chronic ocular diseases to develop more effective therapies.