Project 10: Polymeric transfection agents for drug delivery to treat retinal damage and disease

Diseases of the posterior segment of the eye are increasing considerably, in part due to an ageing population. One such disease, Age-related macular degeneration (AMD), the most common cause of blindness in patients over sixty, accounts for almost 10% of blindness worldwide. Its predicted global incidence for 2020 is 196M, rising to 288M in 2040. Typical treatment involves regular injections into the eye, which is associated with significant patient discomfort and potentially serious side effects, including bleeding, infection and retinal detachment. As such, there is an unmet clinical need for the development of new and improved drug delivery techniques to treat this and similar diseases of the posterior segment of the eye.

This project aims to address this challenge through the development of drug-loaded eyedrops designed for targeted and controlled release of therapeutics for AMD and other posterior segment disease treatment. Novel polymer drug delivery platforms incorporating penetration enhancing agents (PEA) will greatly improve patient comfort and outcomes by negating or reducing the need for ocular injections. Research and experimental work will involve the synthesis, characterization and evaluation of novel polymers incorporating the drug-PEA complexes, that are capable of delivering pharmacologically relevant titres of neuroprotective drugs as dictated by the clinical need. The project is transdisciplinary in nature, incorporating chemical, biomedical, polymeric, industrial and clinical expertise, as well as being highly relevant to patients and industry.

The main phases of the research can be summarised as follows:

• Complete an advanced research training programme in nanotechnology and bioformulation methods for non-invasive drug delivery to the posterior chamber of the eye, together with receiving an enhanced understanding of the underpinning pathophysiology of retinal disease and learning techniques for drug evaluation focussed on relevant in vitro and in vivo models of retinal damage.
• To synthesise a small library of penetration enhancing agents (PEA)
• To evaluate the ability of synthesised PEA to transport therapeutically useful titres of neuroprotective drugs through biological barriers to the retina.
• To assess the capability of eye drops of PEA containing neuroprotective drugs to deliver therapeutic levels of these drugs in a rat/mouse models of ocular injury/disease and to effect similar therapeuticeffects to injected doses