Eye on the Future: Navigating Trends in Ophthalmic Drug Delivery

The World Health Organization estimates that over 2.2 billion people are affected by eye diseases, including glaucoma, conjunctivitis, dry eye disease, and age-related macular degeneration, among others. 

Delivering medication to the eye, however, presents a unique challenge, and in recent years, the burden of these ocular diseases has been a catalyst for significant research and development in the field of ophthalmic drug delivery. To improve treatment efficacy and patient outcomes, researchers and pharmaceutical companies are testing innovative advancements and novel approaches that represent considerable potential.

Working with Dr. Wolf-Ulrich Nickel, a distinguished member of the GL CHEMTEC Scientific Advisory Board, we took a closer look at some of the most exciting advances in ophthalmic drug delivery, the challenges these advances need to overcome, and the role innovative formulation approaches have to play in the future of ophthalmic drug delivery.

Innovative Approaches to Ophthalmic Drug Delivery

A diverse range of approaches are being developed to improve ocular drug delivery, including:

• Traditional topical solutions: Accounting for 90% of the ophthalmic product on the market, topical solutions are still the preferred way to manage ophthalmic disorders due to their easy, non-invasive administration. However, they often struggle with limited corneal penetration and short residence times despite substantial efforts to enhance delivery with adhesive excipients.
• Intracameral and retinal injections: While more invasive, these delivery systems can deliver drugs directly into the eye's interior, achieving higher drug concentrations in specific regions.
• Contact lenses: Contact lenses are being explored to provide controlled or sustained release of medication, potentially improving patient compliance and treatment efficacy.
• Ophthalmic inserts: Inserts offer the potential for extended drug release, but their use can be limited by patient discomfort.
• Iontophoresis: This is a non-invasive technique for drug delivery, but it has limitations related to patient comfort and the type of drugs that can be delivered.

One of the most notable advancements in ophthalmic drug delivery, however, is the development of diverse nanocarrier technologies and carriers. Ranging from 10 nm to 1000 nm in size, nanocarriers currently being tested include: 

• Polymer-based nanocarriers
• Lipid-based nanocarriers
• Saturated lipid nanoparticles
• Nanostructured lipid carriers
• Liposomes
• Cubosomes
• Micro- and nanoemulsions
• Nanosuspensions
• Dendrimers
• Micelles

As highlighted in a recent review by Han et al. (2023), these nanocarriers offer several advantages over conventional delivery methods, including:

• Increased solubility, crucial for enhancing the bioavailability of drugs within the eye.
• Reduced toxicity, minimizing side effects
• Prolonged drug release, potentially reducing dosing frequency
• Facilitated targeted delivery to specific ocular issues, maximizing therapeutic effect and minimizing unwanted systemic exposure

Several innovative approaches have been utilized:

• Triamcinolone nanoparticles significantly enhanced trans-corneal permeation (lit reference)
• Tedizolid phosphate nanocrystals improved solubility and ocular bioavailability (lit ref)
• Hydrophilic moxifloxacin encapsulated lipid-polymer nanoparticles enhanced permeation and bioavailability (lit ref)

Overcoming Common Challenges in Ocular Drug Delivery

Anatomical barriers of the eye become quickly apparent when looking at intricacies of ocular drug delivery. These ocular barriers include:

• The cornea’s multilayered structure and hydrophobic outer layer, which is the primary barrier to drug penetration.
• The conjunctiva that covers the sclera and lines the inside of the eyelids, which presents additional challenges due to its tight junctions and limited permeability. 
• The blood-aqueous and blood-retinal barriers, which further restrict the entry of therapeutic agents into the posterior segment of the eye.

Even if the selected formulation manages to get past these barriers, factors such as tear film turnover and the eye’s natural defense mechanisms can limit drug bioavailability of topically administered medications. The rapid clearance of drugs via tear drainage reduces the time available for absorption, making it challenging to provide treatment within the eye. 

Enhancing Treatment Efficacy: Novel Formulations for Eye Diseases

Reaching target sites within the eye requires innovative approaches to enhance ocular penetration and prolong drug release. 

Nanocarriers, as we have mentioned, offer significant potential in this area. By encapsulating drugs within these carriers, researchers can overcome ocular barriers and achieve sustained and targeted drug release, while also minimizing off-target effects.

Specific examples of nanocarriers being explored for sustained drug delivery in the eye include (Silva-Cunha, 2021):

• Lipoplexes: Formed by nucleic acids and cationic liposomes, these complexes hold promise for both ocular delivery systems.
• Polymersomes and polymeric micelles: Promising for long-acting and targeted IVT drug delivery, with advantages over other nanocarriers, including a lack of harsh manufacturing conditions, encapsulation of both hydrophilic and lipophilic drugs and versatile for particle size, charge, rigidity, shape, and drug release.
• Nanomicellar formulations: Can encapsulate highly hydrophobic drugs and enhance their solubility, which can facilitate drug penetration and its effective delivery to the target tissue.
• Pullulan-dexamethasone conjugates: Formed by linking the drug dexamethasone to the polysaccharide pullulan, these have shown potential as a delivery system with prolonged drug release.

Nanoformulations use the small size and customizable surface properties of nanoparticles and nanoemulsions to increase drug uptake into the cornea (Agarwal et al., 2023). Examples of these tiny drug delivery systems include the eye drops Restasis and Lacrinmune for dry eye disease. These products utilize specific oil-based formulations along with water to deliver medication more effectively compared to traditional formulations.

Mucoadhesive polymers offer another novel approach for ocular drug delivery. These polymers adhere to the mucous membranes on the eye's surface, significantly extending the residence time of medications. According to a review by Peter and Panonnummal, this prolonged contact allows for better distribution and absorption of drugs, ultimately improving treatment outcomes. Additionally, surface modifications can further enhance the interaction between formulations and ocular tissues, optimizing drug delivery to the target site.

Ongoing research and clinical trials are needed to further explore the application of these novel formulations. The good news is that the challenges presented by ocular drug delivery have re-focused research on patient needs and fostered collaboration between researchers, pharmaceutical companies, and Contract Development Manufacturing Organizations (CDMOs).

CDMOs, in particular, will play an increasingly important role in the progress of ophthalmology. providing regulatory, manufacturing, and formulation development expertise that can accelerate the development of more effective, convenient, and patient-centric ophthalmic therapies.

How GL CHEMTEC Can Help 

With a wealth of experience in polymer design, advanced biomedical materials, and tailored drug delivery systems, GLC offers comprehensive solutions to address the complexities of ophthalmic drug delivery.

We provide: 

• Strong organic polymer expertise and advanced biomedical materials applied to medical devices, drug delivery, and ophthalmic applications.
• Unmatched expertise in polymer design and development, including tailored polymers, hydrogels, films, and emulsions/nano-emulsions.
• Experience with advanced custom hydrogels and silicone hydrogels for drug delivery through the eye.
• Full capability of formulation and analytical testing in-house.
• North American facilities, offering a reliable alternative to overseas supply chains and partners.
• A 22-year track record of success based on a highly customer-centric culture.
• ISO 9001:2015 and ISO 13485:2016 certifications.