**Background:** The interest in cannabinoids for medical applications has grown, including for ocular diseases like glaucoma, uveitis, diabetic retinopathy, keratitis, and dry eye syndrome. Cannabinoids interact with the endocannabinoid system (CB1, CB2 receptors) and other targets, offering potential for IOP reduction, anti-inflammatory, neuroprotective, and antimicrobial effects. However, their poor aqueous solubility (e.g., Δ9-THC solubility 1–2 µg/mL, logP 6.42), instability, and ocular barriers (tear film, cornea, blood–retinal barrier) limit topical efficacy. Systemic administration causes side effects (e.g., cardiac effects, anxiety). Thus, advanced drug delivery systems, particularly nanocarriers, are needed to improve ocular bioavailability and reduce adverse effects.
**Methods:** This is a narrative review summarizing literature on cannabinoid-based formulations for ocular administration. It covers studies on glaucoma, keratitis, uveitis, dry eye syndrome, diabetic retinopathy, and Pseudomonas aeruginosa biofilm prevention. The review analyzes physicochemical properties of formulations (size, surface charge, composition) and evaluates outcomes from in vivo and ex vivo studies, focusing on lipid-based nanosystems (nanoemulsions, solid lipid nanoparticles, liposomes) and polymeric systems (nanoparticles, micelles). Key parameters include IOP reduction, corneal permeation, residence time, anti-inflammatory effects, and antimicrobial activity.
**Key Results:** For glaucoma, Δ9-THC in Tocrisolve® reduced IOP by 28% in male mice for ≥8 h (sex-dependent). THC-VHS prodrug in nanoemulsions (sesame oil, polysorbate 80, poloxamer 188) achieved 47% IOP peak reduction for 4 h, similar to timolol but shorter duration (2 h vs. 6 h). THC-VHS solid lipid nanoparticles (Compritol 888 ATO, Pluronic F-68) provided 31% IOP decrease for 480 min, outperforming pilocarpine (120 min) and timolol (180 min). CBD nanoemulsions reduced IOP by 19.9% for 300 min in normotensive rabbits. For keratitis, CBD-loaded micelles (chitosan/PVA/poly(methyl methacrylate)) showed 86% permeation through corneal epithelium under liquid–liquid conditions. CBD nanoemulsions (MCT, polysorbate 80, Solutol HS 15) decreased inflammatory cytokines in a Pseudomonas aeruginosa LPS keratitis model. For uveitis, HU308 in Tocrisolve® reduced leukocyte adhesion and proinflammatory mediators, with higher anti-inflammatory effects than nepafenac, dexamethasone, and prednisolone. For dry eye, Δ9-THC (15% DMSO, 10% Cremophore EL) protected corneal nerve morphology and reduced CD4+ T cell infiltration. For diabetic retinopathy, CBD (IP, 10 mg/kg) reduced ROS and prevented vascular permeability and neuronal cell death. For Pseudomonas aeruginosa biofilms, CBD oil extract (2% w/v) inhibited biofilm formation by ~70% and showed synergistic effect (75%) with multiuse solution.
**Clinical Implications:** Cannabinoid-based nanocarriers offer a promising strategy for ocular diseases by improving drug solubility, corneal permeation, and residence time while minimizing systemic side effects. Lipid-based systems (nanoemulsions, solid lipid nanoparticles) have shown superior IOP reduction and prolonged effect compared to standard treatments (timolol, pilocarpine). However, clinical translation is limited by the need for further optimization of drug loading, release profiles, and biocompatibility. The review emphasizes that while preclinical evidence supports cannabinoid efficacy, no clinical data on ocular nanoformulations exist yet. Future research should focus on targeted delivery, surface modification, and scalable production to advance these therapies to the clinic.