The eye's unique anatomy and physiology pose significant challenges for effective drug delivery. Traditional ophthalmic formulations often show limited bioavailability due to fast clearance, poor tissue penetration, and instability in the ocular environment. Nanotechnology offers a transformative approach by enabling the encapsulation of therapeutic agents within nanoparticles typically ranging from 10 to 200 nm. These nanoscale systems can be engineered for controlled release, targeted delivery, and enhanced stability, providing greater efficiency and precision in reaching ocular tissues.
Nanoparticles leverage their high surface area, tunable size, and modifiable surface properties to overcome anatomical barriers such as the tear film, corneal epithelium, sclera, and retinal layers. They facilitate deeper tissue penetration, prolonged residence time, and improved interaction with specific ocular structures. By incorporating surface ligands, peptides, or functional coatings, nanoparticles can further enhance cellular uptake, tissue-specific accumulation, and biodistribution, offering versatile platforms for anterior and posterior segment applications.
The eye is naturally equipped with multiple barriers that limit effective drug delivery:
Tear Film Clearance: A single 50 μL drop is largely eliminated within two minutes due to tear dynamics, reducing local drug concentration by orders of magnitude.
Corneal Structural Barriers: Tight junctions in the epithelial layer (~2 nm gaps) and the negatively charged stromal matrix restrict penetration of hydrophilic and large molecules.
Aqueous and Retinal Barriers: Tight junctions in the blood–aqueous and blood–retina interfaces, along with active efflux transporters, hinder systemic or topical drug distribution to the posterior segment.
Enzymatic Degradation and Protein Adsorption: Ocular enzymes and protein corona formation can rapidly degrade or sequester drugs, limiting therapeutic efficacy.
These barriers collectively reduce drug bioavailability and necessitate strategies that can protect, retain, and precisely deliver active agents to target tissues.
Nanoparticle-based formulations provide several technological advantages that directly address ocular delivery challenges:
Enhanced Retention and Surface Interaction: Size and charge tuning allow nanoparticles to adhere to the corneal surface, significantly prolonging residence time. For example, cationic surface modifications can increase drug exposure by several-fold.
Improved Barrier Penetration: Particles sized 20–100 nm can traverse corneal and scleral interstitial spaces efficiently, and functional ligands or peptides can facilitate receptor-mediated uptake across retinal layers.
Stabilization of Active Compounds: Nanocarriers protect labile molecules from enzymatic degradation and oxidative stress, maintaining therapeutic potency in the ocular microenvironment.
Controlled and Responsive Release: Polymeric and hybrid systems can achieve sustained release over days to weeks, while stimuli-responsive designs allow on-demand drug release in response to light, pH, or other triggers.
Co-delivery and Synergistic Effects: Mesoporous and composite carriers enable the simultaneous delivery of hydrophilic and hydrophobic agents, supporting multi-targeted or combination strategies for complex ocular pathologies.
Common nanoparticle platforms in ophthalmic applications include liposomes, solid lipid nanoparticles, polymeric micelles, dendrimers, inorganic nanoparticles, hybrid systems, and exosome-mimetic carriers. Each offers distinct advantages in terms of biocompatibility, tissue penetration, release kinetics, and functionalization potential. By integrating these design principles, nanoparticle-based systems are poised to advance ocular drug delivery from frequent, non-specific dosing toward precise, sustained, and targeted therapeutic strategies.
Once a therapeutic agent is released from its formulation, it must navigate the challenges of tear clearance, enzymatic degradation, and complex ocular barriers. Nanoparticles transform "naked" drugs into "carrier-drug complexes," leveraging size, surface properties, and material characteristics to interact dynamically with ocular tissues. Their delivery mechanism can be conceptualized as three parallel pathways, two release patterns, and a responsive surface interface, working in concert to optimize drug localization and retention.
Corneal pathway—epithelium, stroma, and endothelium sequential transport
Flexible lipid-based nanoparticles under 100 nm can penetrate microfolds in the corneal epithelium assisted by tear film dynamics. Positively charged surface modifications, like chitosan, electrostatically interact with the negatively charged E-cadherin at tight junctions, temporarily creating approximately 2 nm gaps to enable lateral particle entry. In the stroma, collagen fiber spacing (~30 nm) and negative charges slow particle diffusion, creating a "stromal reservoir" that sustains gradient-driven drug delivery toward the endothelium. Endothelial efflux transporters, such as P-glycoprotein, are partially shielded by surface polyethylene glycol (PEG) chains, increasing aqueous humor uptake by several folds.
Non-corneal pathway—conjunctiva-sclera-choroid route
The conjunctival epithelium features intercellular gaps up to 10 nm and rich vascularization. Nanoparticles around 20 nm can traverse the scleral collagen layer within 15 minutes after conjunctival administration and move along perivascular spaces to reach the choroidal suprachoroidal compartment. This route bypasses first-pass corneal metabolism, enhancing posterior segment convection and reducing the time to peak vitreous concentration by approximately half compared with topical delivery.
Corneal and scleral marginal pathways
Nanoparticles targeting corneal limbal stem cell niches (vascular pore size 50–80 nm) can be surface-modified with peptides such as CXCR4 antagonists to achieve localized drug enrichment. In experimental models, local drug concentrations can be more than 12 times higher than systemic levels, while avoiding drug exposure to the lens and systemic circulation, providing precise anterior segment targeting.
Diffusion-dominated and erosion-dominated dual-phase release: PLGA nanoparticles (75/25) exhibit an initial diffusion-driven release of ~30% of payload within 48 hours, followed by polymer erosion-mediated near zero-order release of the remaining 70% over approximately 14 days, maintaining stable drug concentrations in the aqueous humor. Although peak vitreous concentrations may be lower than free drug, the overall area under the curve (AUC) can increase up to ninefold, avoiding transient high-concentration fluctuations.
pH- and enzyme-responsive pulse release: Interpenetrating polymer networks of polyacrylic acid and chitosan remain contracted at tear pH (~7.4) to retain drug content. In acidic inflamed microenvironments (pH ~6.5), the network swells, releasing ~80% of drug within 3 hours. Concurrently, upregulated matrix metalloproteinase-2 cleaves surface peptide crosslinks, triggering accelerated pulsatile release proportional to local pathological activity.
Ion-strength-triggered in situ gelation: Calcium alginate nanoparticles undergo ion exchange with Na⁺ in tears, forming a viscoelastic gel within 30 seconds. This increases corneal residence time from ~5 minutes to 45 minutes and improves aqueous drug bioavailability from 2% to 18%, effectively converting a single drop into a sustained ocular depot.
PEG stealth coating: Dense PEG chains reduce protein corona formation by approximately 85%, extend vitreous half-life from 4 hours to 24 hours, and decrease macrophage uptake, resulting in threefold higher drug retention in the choroid.
Charge-reversal strategy: pH-sensitive block copolymers remain neutral at tear pH to minimize nonspecific interactions. Upon reaching endosomal pH (~5.5), tertiary amines protonate, shifting ζ-potential from −5 mV to +18 mV, enhancing endosomal escape and increasing cytosolic drug concentration by approximately sixfold.
Ligand-receptor mediated targeting: Hyaluronic acid-modified nanoparticles bind CD44 on corneal basal epithelial cells, enhancing internalization tenfold. RGD peptide-functionalized lipid nanoparticles specifically recognize αvβ3 integrins on neovascular endothelium, increasing targeted accumulation by eightfold and reducing pathological vascular leakage by 70%.
Glycocalyx-mimetic surface: Sialic acid–PLA copolymers form a brush-like layer that interacts with retinal receptors to evade efflux transporters. Following intravitreal injection, retinal sublayer drug concentrations increase fivefold without compromising cellular viability, balancing high efficiency with biocompatibility.
Fig.1 Nanotechnology drug delivery systems for eye treatment1,2.
BOC Sciences offers versatile nanoparticles engineered for targeted drug delivery and therapeutic applications. Our customized solutions enhance treatment efficacy and precision.
Lipid-based nanoparticles are favored in ocular applications due to their excellent biocompatibility and biodegradability. Solid lipid nanoparticles and nanostructured lipid carriers can encapsulate both hydrophobic and hydrophilic drugs, with the lipid composition finely controlling release kinetics. These systems enhance corneal penetration and intraocular retention.
Liposomes, one of the earliest supramolecular carriers applied in ophthalmology, possess bilayer structures that closely mimic biological membranes. Cationic liposomes not only serve as drug carriers but also facilitate nucleic acid delivery through electrostatic interactions with negatively charged DNA or RNA, improving intraocular transfection efficiency.
Functionalized liposomes achieve precise targeting via surface modifications. PEGylation extends intraocular circulation time, while ligand conjugation enables cell-specific recognition. Temperature- and pH-sensitive liposomes respond to local pathological conditions, allowing controlled and intelligent drug release.
Biodegradable polymeric nanoparticles are widely used in ophthalmology. Synthetic polymers such as poly (lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) offer tunable degradation rates and controlled drug release profiles. Natural polymers, such as chitosan and hyaluronic acid, are prized for their mucoadhesive properties, extending corneal residence time. Gelatin-based nanoparticles provide chemically adjustable degradation rates, enabling tailored therapeutic schedules.
Polymeric micelles formed from amphiphilic block copolymers efficiently solubilize poorly water-soluble drugs and, due to their nanoscale dimensions, penetrate ocular tissues effectively. Stimuli-responsive micelles release drugs in response to pH, enzymatic activity, or redox changes in the eye, enhancing therapeutic precision.
Gold nanoparticles (AuNPs) have diverse applications in ocular imaging and therapy. Their surface plasmon resonance enables biosensing and high-resolution imaging, while photothermal properties allow localized closure of abnormal vasculature, offering minimally invasive treatment for retinal vascular diseases.
Silica nanoparticles, particularly mesoporous silica, feature uniform pore structures for high-capacity drug loading and controlled release. Their large surface area and easy functionalization make them versatile platforms for combined therapeutic and diagnostic applications.
Quantum dots (QDs) are primarily used in ocular imaging but can be surface-functionalized for targeted drug delivery. High brightness and photostability make them ideal for studying intraocular distribution of nanoparticles, providing critical insights for optimizing carrier design. Emerging carbon-based nanomaterials, such as graphene quantum dots, combine exceptional optical properties with drug-loading capabilities, expanding the toolkit for advanced ocular nanomedicine.
Nanoparticle-based formulations have introduced innovative strategies for glaucoma management. Conventional intraocular pressure (IOP)-lowering therapies often face limitations such as low ocular bioavailability and the need for frequent dosing. Nanocarriers enhance corneal penetration and prolong residence time in the anterior chamber, thereby significantly improving therapeutic efficiency. Solid lipid nanoparticles (SLNs) loaded with latanoprost, for instance, demonstrate sustained-release properties, maintaining IOP-lowering effects for over 24 hours with a single administration, which substantially reduces dosing frequency.
Multidrug delivery systems show particular value in combination glaucoma therapy. A single nanoparticle can encapsulate both prostaglandin analogs and β-blockers, enabling precise control over their release kinetics to achieve synergistic IOP reduction. This strategy not only enhances therapeutic outcomes but also minimizes ocular surface toxicity associated with preservatives.
Targeted nanoparticle systems aimed at the trabecular meshwork are under active development. Surface-modified nanoparticles carrying specific peptide sequences preferentially accumulate in trabecular meshwork tissue, enhancing aqueous humor outflow. Advanced systems even carry gene-editing tools to trabecular meshwork cells, enabling regulation of genes involved in fluid drainage and offering a fundamentally new paradigm for glaucoma therapy.
Nanoparticle systems in AMD primarily address the challenges associated with frequent intravitreal anti-VEGF injections. Biodegradable polymeric nanoparticles can encapsulate therapeutic agents such as bevacizumab or ranibizumab, providing sustained release within the vitreous for several weeks to months, thereby significantly extending dosing intervals.
Stimuli-responsive nanoparticles are designed to react to pathological features of AMD, releasing drugs in response to oxidative stress or inflammatory signals. For example, disulfide-containing nanoparticles accelerate degradation in environments with elevated reactive oxygen species, facilitating targeted delivery of anti-angiogenic agents. This on-demand release approach enhances therapeutic precision and efficiency.
Emerging nanoparticle strategies for geographic atrophy focus on neuroprotection and complement system modulation. Nanoparticles serve as carriers for neuroprotective agents and complement inhibitors, slowing the degeneration of retinal pigment epithelium and photoreceptor cells. Certain systems also deliver neurotrophic factors to promote retinal cell survival, offering promising avenues for disease modification.
Nanomedicine approaches for diabetic retinopathy (DR) target multiple pathological mechanisms, including vascular leakage, inflammation, and neurodegeneration. Multifunctional nanoparticles can concurrently target several disease pathways. For instance, nanoparticles loaded with anti-inflammatory and antioxidant agents synergistically reduce retinal inflammation and oxidative damage.
Penetration of the blood-retinal barrier (BRB) remains a critical challenge in DR therapy. Functionalized nanoparticles can traverse this barrier via receptor-mediated transport. Transferrin receptor-targeted nanoparticles, in particular, demonstrate high retinal specificity, providing an ideal platform for gene-silencing therapeutics.
In inflammatory ocular disorders such as uveitis, nanoparticles exploit enhanced permeability and retention (EPR) effects to accumulate preferentially at inflamed sites. Dexamethasone-loaded nanoparticles exhibit prolonged anti-inflammatory effects in experimental uveitis models, controlling inflammation for weeks with a single administration. Targeting inflammatory cells further increases the precision of immunomodulatory interventions.
BOC Sciences continues to invest in research and development in the field of ocular nanocarrier research, dedicated to advancing the scientific development of ocular drug delivery systems. The company has established a systematic technological capability in nanocarrier design, characterization and evaluation, customized formulation development, and collaborative innovation, significantly improving the research and development efficiency and performance optimization of ocular nanocarriers. This provides the industry with sustainable solutions and scientific support.
Table 1. Ocular Nanocarrier Products for Precision Medicine.
| Product Name | Product Description | Applicable Fields | Inquiry |
| Lipid Nanoparticles | Used for encapsulating both hydrophilic and lipophilic drugs, improving corneal penetration and ocular retention time. | Glaucoma, AMD, Diabetic Retinopathy, Local Ocular Treatment | Inquiry |
| Solid Lipid Nanoparticles (SLNs) | Provides sustained release properties, suitable for the treatment of glaucoma and other diseases. | Glaucoma, Intraocular Pressure Management | Inquiry |
| Polymeric Nanoparticles | Adjustable degradation rates, enhancing local therapeutic effects of drugs for ocular drug delivery. | Chronic Ocular Diseases, Ocular Drug Delivery | Inquiry |
| Liposomes | Bilayer structures mimicking biological membranes, improving drug release in the eye and facilitating nucleic acid delivery. | Gene Therapy and Drug Delivery for Ocular Diseases | Inquiry |
| Gold Nanoparticles | Exhibits photothermal properties, useful for ocular imaging and treatment, ideal for retinal vascular diseases. | Retinal Diseases, Ocular Imaging | Inquiry |
| Quantum Dots | Excellent optical properties, useful for ocular drug delivery and imaging monitoring. | Ocular Imaging, Ocular Drug Delivery | Inquiry |
| PLGA Nanoparticles | Achieves long-term controlled release of drugs, providing sustained therapeutic effects. | Glaucoma, Age-Related Macular Degeneration, Diabetic Retinopathy | Inquiry |
In nanocarrier design, BOC Sciences integrates nanomaterial science and drug delivery technologies to achieve precise construction of ocular-specific carriers. The company conducts systematic optimization on key parameters such as nanoparticle size, surface charge, and hydrophilic-lipophilic balance, aiming to improve the distribution characteristics of the carriers in the cornea, sclera, and vitreous body. The research team has also explored functional surface modification techniques, including ligand modifications and the introduction of responsive materials, to enhance the targeting and controlled release capabilities of nanocarriers in the ocular microenvironment. By combining computational simulations with experimental validation, BOC Sciences is able to predict carrier performance in the early stages, significantly reducing experimental iteration costs and accelerating the development of high-performance nanocarriers.
In characterization and quality evaluation, BOC Sciences has established a multidimensional analysis system that includes physical-chemical properties, structural stability, and biocompatibility indicators. The company utilizes techniques such as particle size distribution, zeta potential measurement, morphological observation, thermodynamic and spectroscopic analysis to comprehensively assess the preparation quality and consistency of nanocarriers. Additionally, in vitro drug release profiles and stability tests are used to validate the functionality of the carriers in simulated ocular environments. This series of evaluation methods provides a scientific basis for subsequent formulation optimization, while ensuring the controllability and reproducibility of the nanocarriers in terms of material characteristics and functional performance.
In formulation development, BOC Sciences emphasizes customization and adjustability, designing personalized nanocarrier systems based on the characteristics of different drug molecules and ocular delivery requirements. The company develops formulations that include liposomes, polymeric nanoparticles, and composite material carriers. By optimizing drug loading efficiency, release rates, and adhesion properties, the company ensures precise delivery and high bioavailability. For different application scenarios, such as anterior chamber, vitreous body, or corneal local delivery, the team can adjust carrier size, surface modifications, and drug loading amounts to achieve targeted delivery and controlled release, providing diversified solutions for ocular drug development.
Table 2. Tailored Nanoparticle Solutions for Ocular Drug Delivery.
| Service Name | Service Description | Inquiry |
| Nanocarrier Design and Optimization Services | Provides nanocarrier design for ocular diseases, including optimization of particle size, surface charge, and drug loading. | Inquiry |
| Customized Ocular Drug Formulation Development Services | Offers tailor-made ocular drug formulations, optimizing drug loading efficiency, release properties, and adhesion. | Inquiry |
| Nanoparticle Characterization and Quality Evaluation Services | Provides comprehensive nanoparticle characterization, including particle size distribution, surface charge, stability, and drug release profiles. | Inquiry |
| Surface Functionalization Technology Services | Introduces ligand modifications or responsive materials to enhance drug delivery accuracy and targeting. | Inquiry |
In terms of technology translation, BOC Sciences focuses on interdisciplinary collaboration and industrial chain integration, accelerating the application of nanocarrier technology through partnerships with materials science, pharmaceutical chemistry, and engineering fields. The company provides comprehensive R&D support, ranging from early-stage carrier design and characterization validation to customized formulation development, helping partners shorten experimental cycles and improve R&D efficiency. In addition, the team actively participates in academic exchanges and joint research projects, rapidly translating the latest scientific research findings into applicable nanocarrier systems, and driving the industrialization of ocular nanodrug delivery technologies.
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