The human eye is incredibly resilient. It has several physiological barriers to resist penetration of foreign molecules and particles, which makes drug delivery to the eye a real challenge.
The last 20 years have seen continual progress in both the availability of new ocular therapies and novel delivery mechanisms (especially for chronic and age-related eye disorders such as glaucoma and macular degeneration).
All forms of delivery to the eye can be stressful for patients but the growth of the ophthalmic drug market in the last few years has driven ground-breaking innovations to reduce stress and improve patient outcomes. These include: advancements in less frequent, longer acting injectables, development of ocular implants with a slow release system and less-invasive solutions such as drug-eluting contact lenses.
When developing ocular delivery devices, designers and manufacturers must address several challenges:
• maintaining device sterility to prevent infections
• controlling dosing accuracy (especially when delivering small/concentrated volumes)
• managing the opportunities for use errors during the delivery process, such as poor needle and plunger control with injection devices
All of the above challenges could harm the patient and significantly compromise their treatment outcome.
In this blog, I will look at the main ocular drug delivery routes and highlight some of the associated challenges. Before we start, it’s important to consider that ocular disorders are typically designated in two ways:
Anterior segment: this refers to pathologies of the front of the eye such as dry eye, cataract and allergic conjunctivitis
Posterior segment: eye diseases involving the back of the eye, for example, diabetic retinopathy, diabetic macular edema and wet age-related macular degeneration (wet AMD)
Approximately 90% of all ocular therapeutics are delivered topically, usually via drops or as a fine mist spray using either a dropper bottle or a metered dose pump. This is the preferred method for delivery of therapeutic agents to the anterior eye segment as it is the least invasive and patients can often administer the therapy for themselves. The main challenges for topical delivery are both dosing, considering the low proportion of drug which actually enters the eye (low bioavailability), and patient compliance. Patient compliance is crucial, especially with elderly patients and when frequent administration is required.
This is where a therapeutic is injected underneath the eyelid into the eyeball, also called conjunctiva. This type of drug delivery to the eye is performed mainly for the treatment of lesions, glaucoma or cytomegalovirus retinitis (CMS). The subconjunctival route bypasses the epithelium (the main barrier to drug entry into the eye). This approach is relatively common, but it can be distressing for patients and depending on the volume injected, a portion of the drug can leak on the surface of the eye and mix with tear film, reducing efficacy.
Intravitreal injections involve the administration of small volumes of drug, typically between 20 and 100 µL into the vitreous – the jelly like fluid inside the eyeball. Injections are prepared by technicians and administered by experienced retina specialists in clinical settings. The standard of care is to inject the patient using various types of devices such as syringe and vial or pre-filled syringes. This route is very effective for treating a range of retinal diseases such as AMD as it can easily bypass all ocular barriers. However, this type of injection to the eye is invasive and can sometimes cause retinal damage as it is less targeted than other methods of ocular delivery.
The therapeutic agent is injected at the front of the eye but travels to the choroid and retina. This delivery route is indicated for patients with neovascular age-related macular degeneration, diabetic retinopathy, uveitis and more. The main advantage is that this technique delivers the drug to specific tissues at high concentrations, as opposed to being spread into both affected and healthy tissues. However, this method does require extra training for healthcare professionals, especially if microneedles are used as preparation and delivery of small liquid volumes can be challenging.
This technique is performed in an operating room and is the standard method for injecting gene therapy for people with retinal diseases. This drug delivery route is very targeted but also very invasive and can lead to complications and additional risks for patients.
For the last 15 years, treatment options for people with retinal diseases have been limited. While intra ocular injections are effective in treating diseases, many patients require regular monthly (or bi-monthly) injections to optimise drug efficiency. More recently, cutting-edge ocular implants have been revolutionising the treatment of retinal diseases. Current implants come in two categories: biodegradable (bioresorbable – which are inserted and absorbed by the body over time) and non-biodegradable (biodurable – implants that do not break down in the eye and have to be removed or refilled once the treatment is complete).
A prime example of a biodurable implant is the port delivery system developed by Genentech/Roche to deliver ranibizumab for the treatment of wet, or neovascular age-related macular degeneration (AMD). The port device is implanted surgically and is a permanent refillable eye implant, approximately the size of a grain of rice, designed to continuously deliver a customised formulation of ranibizumab over a period of months. This process can reduce the treatment burden associated with frequent eye injections. Other examples of a bioabsorbable implant is Allergans Ozurdex® – a small implant that slowly releases corticosteroid medication over time, without the need for monthly injections. It dissolves naturally and does not need to be surgically removed.
Overall, implants offer patients many improvements for ocular treatments compared to injections. However, the development of manufacturing controls to ensure homogenous drug concentrations is essential. In addition, the development of surgical procedures, including identification and assessment of associated human factors risks, require considerable expertise to manage.
At Team Consulting, we have a 35-year history of developing novel drug delivery technologies to treat a wide range of therapy areas. We would be delighted to talk about how we can help solve your ocular delivery challenges. Get in touch.
Robin G Stanley, Subconjunctival Drug Administration. Small Animal Clinical Pharmacology (Second Edition), 2008.
Shelley E. et al. Biomechanics of Suprachoroidal Drug Delivery: From Benchtop to Clinical Investigation in Ocular Therapies. Expert Opinion on Drug Delivery, 2021, Vol. 18 Issue 6.
Gote V. et al. Ocular Drug Delivery: Present Innovations and Future Challenges. Journal of Pharmacology and Experimental Therapeutics, 2019, Vol. 370 Issue 3.
Timo Kangastupa, A New Platform ofr Suprachoroidal Drug Delivery Using Standard Commercially Available Needles. ONdrugDelivery, 2022, Issue 130.
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