**Background:** Dry eye disease (DED) is a multifactorial ocular surface disorder affecting 5%–50% of the global population, with increasing prevalence due to risk factors such as drug use, eye surgery, environmental conditions, and contact lens wear. Conventional topical treatments—including artificial tears, cyclosporine, corticosteroids, mucin secretagogues, and NSAIDs—suffer from low bioavailability (<5%), rapid drug metabolism, and frequent administration requirements. Nanomedicine offers solutions by enhancing drug delivery, prolonging residence time, and improving patient compliance.
**Methods:** This is a narrative review that synthesizes published literature on the pathogenesis of DED, current clinical treatments, and the application of various nanocarrier systems for DED therapy. The review categorizes nanocarriers into polymeric nanoparticles (e.g., dendrimers), inorganic nanoparticles (e.g., silica, gold, cerium oxide), and lipid-based nanoparticles (e.g., liposomes, nanoemulsions, nanostructured lipid carriers). It also summarizes commercially available nanomedicines and preclinical/clinical studies.
**Key Results:** The review reports that several nanoformulations have received regulatory approval: Restasis® (0.05% cyclosporine A nanoemulsion, FDA-approved 2002), Cequa® (0.09% cyclosporine A micellar solution, FDA-approved 2018), Ikervis® (0.1% cyclosporine A cationic nanoemulsion, EMA-approved), and Xiidra® (5% lifitegrast solution, FDA-approved). Preclinical studies demonstrate that dendrimer-dexamethasone conjugates reduce infiltration in rabbit models of autoimmune lacrimal gland inflammation. Nanoemulsions such as Clacier® (0.05% CsA) showed significant improvement in corneal fluorescein staining scores after 12 weeks compared to baseline. Micellar formulations (e.g., Cequa®) exhibited a 4.5-fold increase in ocular retention versus 0.05% CsA emulsion. Nanosuspensions achieved corneal CsA concentrations of 1683 ± 430 ng/g cornea, surpassing Restasis® (350 ng/g) and cationic emulsion (750 ng/g). Liposomal sprays (Tears Again®) and Trimix® eye drops improved tear film stability and patient symptoms over two months. Nanostructured lipid carriers (NLCs) loaded with dexamethasone showed slower tear concentration decline and higher peak concentrations than TobraDex®. Inorganic nanoparticles—including gold nanoparticles loaded with amfenac (fluorescein staining score ~5 times lower than CsA group), cerium oxide nanoparticles that restored goblet cell count and morphology, and silica nanoparticles with minimal cytotoxicity—demonstrate potential for DED treatment.
**Clinical Implications:** Nanomedicine addresses key limitations of conventional DED therapies by improving drug bioavailability, enabling sustained release, reducing dosing frequency, and minimizing side effects. The approval of multiple nanoformulations (Restasis®, Cequa®, Ikervis®, Xiidra®) validates the clinical utility of nanotechnology in DED management. However, challenges remain in biocompatibility, scale-up, drug release optimization, and pharmacokinetics. Further research is needed to translate these innovations into widespread clinical practice.