Nanomaterials in Ophthalmology: A Review

Eye diseases are becoming more common. In 2020, over 250 million people had mild vision problems, and 295 million experienced moderate to severe ocular conditions.

In response, researchers are turning to nanotechnology and nanomaterials—tools that are transforming how we approach eye health. These technologies are improving how drugs are delivered to the eye and supporting new developments in tissue engineering for ocular treatments.¹

Using Nanomaterials to Optimize Ocular Drug Delivery

Delivering therapeutic drugs directly to the eyes is a primary strategy in ophthalmic treatment. However, traditional methods often struggle to penetrate the ocular barrier, limiting drug effectiveness at the intended site and duration.

Nanomaterial-based carriers offer a promising solution—they can bypass this barrier, enable controlled and targeted delivery, and reduce dosing frequency.

Nanomicelles: Targeted Delivery Through Core-Shell Carriers

Nanomicelles are a key tool in ophthalmic drug delivery. These core-shell structures are made of amphiphilic polymers, with a hydrophobic core and a hydrophilic shell. This architecture allows them to encapsulate hydrophobic drugs and transport them through the eye’s protective layers.

Positively charged nanomicelles are particularly effective in delivering hydrophobic drugs to various parts of the eye. Reverse nanomicelles, meanwhile, encapsulate drugs within their core, improving stability, enabling sustained release, and reducing potential side effects.

Nanomicelles made from tocopherol polyethylene glycol 1000 succinate (TPGS) and Solutol® HS15 have been used to deliver the immunomodulatory drug cyclosporine. These nanocarriers—loaded with 5 mg/mL of cyclosporine—enabled targeted, long-lasting drug delivery to the cornea and sclera.

Another innovation includes chitosan oligosaccharide valylvaline-stearic acid (CSO-VV-SA) nanomicelles, designed for precise drug delivery to corneal tissues and epithelial cells.

Nanoemulsions in Ocular Drug Delivery

Nanoemulsions are kinetically stable formulations with droplet sizes ranging from 10 to 500 nm. They have demonstrated improved drug retention on the anterior corneal surface, better penetration through ocular barriers, and increased bioavailability compared to conventional formulations.

A cationic ophthalmic nanoemulsion containing 0.5% (w/w) chitosan and a nonsteroidal anti-inflammatory drug has been applied in the treatment of ocular surface diseases. It supports tear film stability and enhances drug delivery in managing Dry Eye Disease (DED).

For bacterial keratitis—a serious infection that can lead to visual impairment—a ciprofloxacin-loaded nanoemulsion (CIP-NE) was developed. This spherical formulation showed a zeta potential of −35.1 ± 2.1 mV and a polydispersity index of 0.13 ± 0.01.

In trans-corneal studies, CIP-NE achieved 2.1 times greater drug penetration than commercial ciprofloxacin, indicating its potential for improved treatment efficacy.³

Nanofibers in Ocular Drug Delivery

Nanofibers offer a high surface-to-volume ratio, good mechanical strength, and effective drug-loading capacity, making them suitable for ocular drug delivery. Electrospun polymeric fibers containing gentamicin and dexamethasone have been developed for the treatment of bacterial conjunctivitis.

These fibers dissolve in tear fluid and release the drugs at the site of infection. In one study, the formulation achieved a 92 % treatment success rate. Drug availability on the ocular surface increased by 342 % after approximately 320 minutes, indicating prolonged retention and sustained release.⁴

Nanomaterials in Ophthalmic Diagnostic Imaging

Imaging is essential for monitoring eye disease progression and evaluating treatment outcomes. Nanomaterials are being applied to improve contrast in techniques such as photoacoustic microscopy and optical coherence tomography.

Indocyanine green (ICG) has been used to label human retinal pigment epithelial cells (ARPE-19) in regenerative therapy research. One approach combines ICG with chain-like gold nanomaterials and RGD peptides, forming ICG-CGNP-clustered RGDs. These ~50 nm particles enable effective cell labeling and allow non-invasive tracking of stem cell movement in the eye.

Gold-based nanoparticles (GNPs)—including nanowires, nanoshells, and nanodisks—have been studied for their imaging contrast properties. Gold nanobipyramids, sized between 130–180 nm, have improved the sensitivity of optical coherence tomography by enhancing optical scattering. Their biocompatibility and tunable localized surface plasmon resonance (LSPR) properties support their use in ophthalmic imaging.⁵

Role of Nanomaterials in Ocular Tissue Engineering

Tissue engineering supports the development of stem cell-based therapies and the regeneration of damaged ocular tissues. Certain nanomaterials, such as nanofibers, are well-suited for this purpose due to their biocompatibility and surface properties that promote cell adhesion.

In experimental studies, nanofiber scaffolds have been shown to support full re-epithelialization of human corneal tissue. They have also been investigated for their role in modulating anti-inflammatory gene expression.⁶

Nanostructured dendrimers are another class of materials being explored for corneal tissue repair. These materials offer high-density functional side chains, potential for cross-linking, and scalability. Dendrimer-based hydrogels have been applied in corneal tissue engineering without signs of inflammation or infection. Their structural properties support wound closure and the regeneration of healthy corneal tissue.⁷

Regulatory and Safety Considerations

The development and approval of nanomaterial-based therapies for ophthalmic use present regulatory challenges that differ significantly from those of conventional drugs. Currently, there are no standardized protocols for assessing the toxicity of nanomaterials in the distinct layers of the eye.

Regulatory agencies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have stringent requirements for demonstrating the safety and biocompatibility of nanomaterials. These include validated manufacturing processes to ensure batch-to-batch consistency, compliance with Good Manufacturing Practice (GMP), stability testing, and sterility for ocular formulations. These added steps increase both the complexity and cost of product development.

Safety testing must also evaluate potential oxidative stress, biocompatibility, and effects on cellular viability. Delivering drugs to specific regions of the eye—such as the vitreous body or retina—remains difficult due to the eye’s compartmentalized anatomy and active clearance mechanisms.

While increasing the drug dose might seem like a solution, it carries risks such as inflammation, cytotoxicity, or increased intraocular pressure. These risks are especially serious in sensitive tissues like the retina, where damage could lead to permanent vision loss, emphasizing the importance of precise dosing strategies.

Ongoing research aims to address these challenges by improving the precision and duration of nanomaterial-based drug delivery in the eye.⁸

Emerging Tools and Technologies in Ocular Medicine

Emerging research is exploring the integration of nanotechnology with advanced genetic tools, such as CRISPR-Cas systems, to develop targeted therapies for ocular diseases. These approaches may enable the correction of multiple genetic defects involved in complex eye conditions.⁹

Researchers are also investigating the use of nanoscale robotic systems for high-resolution imaging, with the potential to replace traditional contrast agents and dyes. Advances in sub-atomic tuning of nanomaterials may support the development of more precise and adaptable therapies for ocular conditions.

As these technologies mature, they could contribute to improved diagnostic imaging, biosensing, and drug delivery strategies aimed at managing and preventing serious eye diseases.

To keep up with the latest breakthroughs in diagnostics, therapeutics, and next-generation nanotechnologies, subscribe to our expert-curated Nanomedicine Newsletter.

References and Further Reading

1. Bourne, R., et. al. (2021). Trends in prevalence of blindness and distance and near vision impairment over 30 years: an analysis for the Global Burden of Disease Study. The Lancet global health. Available at: https://doi.org/10.1016/S2214-109X(20)30425-3
2. Xu, X., et. al. (2020). Functional chitosan oligosaccharide nanomicelles for topical ocular drug delivery of dexamethasone. Carbohydrate polymers. Available at: https://doi.org/10.1016/j.carbpol.2019.115356
3. Youssef, A., et. al. (2021). Design of Topical Ocular Ciprofloxacin Nanoemulsion for the Management of Bacterial Keratitis. Pharmaceuticals. Available at: https://doi.org/10.3390/ph14030210
4. Li, S., Chen, L., Fu, Y. (2023). Nanotechnology-based ocular drug delivery systems: recent advances and future prospects. Journal of nanobiotechnology. Available at: https://doi.org/10.1186/s12951-023-01992-2
5. Nguyen, V., et. al. (2024). Advanced nanomaterials for imaging of eye diseases. ADMET and DMPK. Available at: https://doi.org/10.5599/admet.2182
6. U, Egemen., et. al. (2023). Nanofibers in Ocular Drug Targeting and Tissue Engineering: Their Importance, Advantages, Advances, and Future Perspectives. Pharmaceutics. Available at: https://doi.org/10.3390/pharmaceutics15041062
7. Mijanović, O., et. al. (2021). Tissue Engineering Meets Nanotechnology: Molecular Mechanism Modulations in Cornea Regeneration. Micromachines. Available at: https://doi.org/10.3390/mi12111336
8. Mahaling, B., et. al. (2024). Nanomedicine in Ophthalmology: From Bench to Bedside. Journal of Clinical Medicine. https://doi.org/10.3390/jcm13247651
9. Mehta, N., et. al. (2024). Nanotechnology in retinal disease: Current concepts and future directions. Journal of Ocular Pharmacology and Therapeutics. https://doi.org/10.1089/jop.2023.0083