Injectable devices for sustained ocular drug delivery

This Healthcare Impact Partnership will use drug delivery technologies previously invented by us to develop novel, injectable devices to provide targeted, controlled and sustained drug delivery to the inside of the eye. These devices will address unmet clinical needs in two groups of patients. In addition, we will develop sophisticated benchtop and computer models of drug release in the eye, to allow us to speed up development and reduce the amount of animal testing required to use the devices in humans.

Over 5.7 million people in the UK are living with sight-threatening eye conditions. These include conditions that can develop as a result of diabetes, macular degeneration and retinal detachment. The current best practice for treatment of the scarring that can follow retinal detachment is injection of silicone oil into the eye to replace the vitreous. It has been proposed that, in addition to the oil, sustained drug delivery could help reduce the development of scarring. We have previously developed technology to achieve controlled, extended release of drugs from silicone oils, and now wish to apply these technologies to silicone oils that are suitable for use in patients. Treatment for other sight-threatening conditions requires patients to have frequent injections of drugs directly into the eye over many years. This can be uncomfortable and inconvenient for patients, places a burden on the healthcare system and is not feasible in developing countries. A small number of drug delivery devices that reduce the number of injections needed are available, but these must either be removed once the drug release is complete, or, if the device is degradable, do not last much longer than standard injections. We have previously developed technology to make drugs into nanoparticles. We will develop a drug delivery system constructed of nanoparticles inside a material that forms a gel when it is injected into the eye. After the drug has been released, the gel would degrade into non-toxic components. The advantages of this over existing devices are that this technology could be tailored in terms of the drug and dosing, and that higher doses will be possible due to the use of nanoparticles. Both of our delivery devices are injectable, and will improve patient outcomes, particularly in developing countries and patients that present late.

Our team is multidisciplinary, including academics specialising in ophthalmic biomaterials and drug delivery. A clinical ophthalmologist specialising in drug delivery will ensure that our technologies are suitable for clinical use. We will also engage with patients groups, who will help inform our development strategy. In order to accelerate the technologies towards the production of devices that are suitable for use in patients, we have partnered with a company who manufacture silicone oil products used to treat retinal detachment. With their expertise, we will be able to ensure that we include certain crucial aspects as we develop our technologies, such as how to scale up manufacture from the laboratory to that suitable for commercial use, and the generation of data that is required for the products to gain a licence for clinical use. Another commercial partner specialising in the production of models to replace animal testing will help us optimise our models, and promote their use to other organisations who are interested in reducing animal use.

We will apply our silicone oil-based drug release technology to commercially-available oils, ensuring the resulting product has appropriate physical properties to remain functional in the eye, is not toxic, and has optimal drug release. We will also develop our nanoparticle system, optimising physical, drug-release and toxic properties. At the same time, we will develop existing benchtop and computer models so that they will be able to predict drug release from our devices.

Commercial impacts: the technology to be developed in this proposal, funded previously by EPSRC, has been protected by patent filings, and team members have experience in IP protection and licencing. Protection of emerging IP will help strengthen commercial impacts and provide more opportunities for future development. The development of novel, injectable drug delivery devices presents a significant market opportunity to industrial partner Fluoron GmbH, who have a track record of commercialising silicone oil technologies developed in universities, and this partnership provides a proven route towards achieving healthcare and commercial impacts from the technology. Their close involvement will also help de-risk the next stage of investment, making future development more cost-effective for investors, developers and, ultimately, customers. The second industrial partner, Kirkstall Ltd, is a UK-based SME which produces "organ-on-a-chip" models to replace the use of animals in medical research. The models developed within this proposal will help extend their product portfolio and attract more customers from the pharmaceutical industry. The models will accelerate the development of future treatments, meaning they can be brought into clinical use more rapidly and at a much lower cost.

Healthcare impacts: there is an unmet clinical need for injectable, sustained drug delivery to the eye. Patients will benefit from this technology by way of a reduction in uncomfortable and time-consuming clinic visits, and better outcomes, as well as a reduction in the chance of complications. Those in developing countries may have a new, practical solution for treatment. At the same time, healthcare systems will gain a cost-effective means of delivering treatment and improving clinical outcomes. Patient involvement will benefit the project team, and connect patients to research. The clinical partner will have the opportunity to input into the project, which will lead to more rapid development of effective treatments for his patients and, if the technology progresses to clinical studies, increase institutional prestige.

Societal impacts: outreach and engagement activities will bring societal impact. Interaction with patient groups will increase patient knowledge of advances in treatment, and may encourage their engagement in their own treatment and inspire lobbying for the funding of eye research. Communication to public and schools events will also help raise awareness about eye health and research. The targeting of under-represented student groups will help inspire the next generation of scientists and engineers, and also raise aspirations in those students, another important societal impact. The benchtop and computer models developed within this proposal bring significant ethical impacts, as they will reduce animal use in this and future projects, both academic and commercial.

Researcher and academic impacts: VK will gain significant experience in managing a multi-partner project, formal training in regulatory issues and electrophysiology, all of which will help her develop towards being a leader in ophthalmic biomaterials. TM and SR will be able to extend their research to a new clinical area. The project will deliver skills training and experience of working on a truly multidisciplinary project to the PDRAs. Both will experience research in a commercial setting, and PDRA1 will gain exposure to clinical research that is not common for a polymer chemist. Clinical trainees will also experience laboratory research, helping to bridge the gap between clinical and academic researchers. There will also be a knowledge impact for a wide range of academics interested in ocular drug delivery, nanomedicines and models for testing drug delivery technology. All of these contribute towards strengthening the UK research base.