Drug delivery methods based on nanotechnology for the treatment of eye diseases

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TL;DR

This narrative review summarizes recent advances in nanotechnology-based ocular drug delivery systems, including nanoparticles, liposomes, and nanomicelles, for treating anterior eye diseases. These systems offer improved bioavailability, targeted and sustained release, and reduced side effects compared to conventional therapies, but face challenges in biocompatibility, scaling, and clinical translation. The review highlights ongoing clinical trials for conditions like dry eye, glaucoma, and cataract, and emphasizes the need for safer, more stable nanoformulations.

Full summary

4,200 CHARS

**Background:** Ocular drug delivery is challenging due to the eye's unique anatomical and physiological barriers. Despite effective medications for ocular diseases, conventional delivery methods (e.g., eye drops, injections) suffer from low bioavailability, frequent dosing, and systemic side effects. Nanotechnology offers potential solutions by enabling targeted, sustained, and controlled drug release at the nanoscale. This narrative review aims to highlight recent developments in nano-based technologies for the detection and treatment of ocular diseases, focusing on anterior segment eye diseases (ASEDs).

**Methods:** The authors conducted a comprehensive review of the literature on nanotechnology-based ocular delivery systems (NODS). They describe the materials and procedures used in NODS, including polymers (natural like chitosan, hyaluronic acid, alginate; synthetic like PLGA, PEG, PAMAM), lipids (triglycerides, fatty acids, phospholipids), surfactants (polysorbates, poloxamers), and active pharmaceutical ingredients (anti-inflammatory, immunosuppressive, antiglaucoma drugs, phytochemicals, genes). Characterization techniques for NODS are detailed: particle size (dynamic light scattering), zeta potential, surface morphology (SEM, TEM), lipid crystallinity (DSC, PXRD), entrapment efficiency and drug loading (centrifugation at 10,000–20,000 rpm for 10–30 min, followed by spectrophotometry or HPLC), drug release/permeability (Franz diffusion cells with phosphate buffer pH 7.4 or simulated tear fluid at 37°C), mucoadhesion and ocular retention (fluorescence imaging, gamma scintigraphy), stability, and toxicity (Draize test, HET-CAM, cell viability assays). The review also summarizes clinical trials for NODS and discusses biosafety, challenges, and comparisons with conventional methods.

**Key Results:** The review identifies several NODS under clinical investigation: a Phase II trial (NCT03001466) of urea-loaded polymeric nanoparticles (Pluronic F-127) for cataract, comparing to placebo eye drops five times daily for 8 weeks, with visual acuity assessed at 6 months. A Phase III trial (NCT02845674) of 0.09% cyclosporine nanomicellar solution (OTX-101) for dry eye included 258 participants aged ≥18 years. A Phase II trial (NCT02466399) compared subconjunctival liposomal latanoprost (POLAT-001) to latanoprost ophthalmic solution in 80 patients with open-angle glaucoma or ocular hypertension, measuring intraocular pressure difference after 3 months. Other trials include phospholipid liposomal spray for dry eye (NCT02420834), dexamethasone nanoparticles for post-operative inflammation (NCT04130802), and omega-3 fatty acid microemulsion (NCT02908282). Biosafety data show that chitosan-coated liposomes increased penetrability and bioavailability (3.9 and 2 times, respectively) compared to uncoated liposomes with timolol maleate, with sustained drug release for 4 and 2 hours. In a Phase III study of Cequa (cyclosporine nanomicelles) for dry eye, 744 participants showed significantly improved Schirmer scores versus vehicle, with >5% reporting adverse effects. Fluconazole nanoemulsion in-situ gel was nontoxic at 0.1% and 0.5% doses in retinal cell viability assays and non-irritating per Draize and HET-CAM tests. Everolimus-loaded nanomicelles (Soluplus) showed comparable efficacy and safety for uveitis with no or moderate irritation.

**Clinical Implications:** Nanotechnology-based drug delivery systems hold promise for improving treatment of anterior eye diseases by enhancing drug bioavailability, enabling sustained release, and reducing systemic side effects. However, clinical translation is slow due to challenges in scaling up, biocompatibility concerns, and the inability of animal models (e.g., rodents, rabbits) to fully replicate human ocular physiology. The review emphasizes the need for safer, less toxic, and stable nanoformulations, and suggests combining drugs with enzyme inhibitors to improve absorption. Emerging technologies like hydrogel templates and mucus-penetrating particles may further enhance efficacy. Ongoing clinical trials indicate progress, but more work is required to bring affordable nanomedicines to market.