An Injectable Implant Providing Long-Acting Drug Delivery for the Treatment of Chronic disease

Within Europe, chronic diseases are currently the leading cause of mortality and morbidity. In England alone, there are 15m people with long-term conditions who are estimated to account for 70% of the total health and social care spend. A significant factor in the management of chronic disease is the long-term nature of the treatment. Although often very efficient, therapies are only effective when combined with long-term medication adherence from the patient. Unfortunately, patient adherence is typically poor within long-term disease patient populations; only about 50% of patients adhere to their treatment regimes. Poor adherence can be addressed by the simplification of therapeutic regimes through reducing the dosing frequency. For example, when self-administered treatment regimens such as oral dosing are replaced with long acting formulations adherence can be greatly improved. Additionally, reducing the frequently of dosing is known to be appealing to patients with long-term therapy requirements.

This proposal seeks to develop a new drug delivery system that could be easily injected into the body and would provide long-acting drug release. This technology would address issues caused by poor medication adherence. The drug delivery system would be composed of responsive polymer nanoparticles and drug nanoparticles that form a nanocomposite, entrapping a reservoir of drug upon injection into the body. After the drug has been released the materials would degrade into non-toxic components and leave the body.

In order to accelerate the development of this novel technology toward clinical use, this project will consist of closely-integrated materials synthesis and biological assessment. The materials involved will be simultaneously prepared and evaluated in the presence of cells to check that they are biologically compatible. The responsive polymer nanoparticles will be synthesised to combine responsive behaviour with tuneable degradation, while the design of the drug nanoparticles will allow the drug release rate to be altered. A small number of optimised materials will undergo detailed biological evaluation. The resulting novel, biodegradable, nanocomposite material would have appropriate physical and biological properties for injection into the body. This technology will provide tuneable, long-acting release of drugs for the treatment of chronic disease.

Economy:
Long-acting drug delivery provided by a single injection would be a major step forward for the treatment of chronic disease. Relevant utilisation of this research will provide significant benefits for the pharmaceutical industry and the healthcare sector. The burden on the NHS associated with chronic disease is huge, estimated at £77bn per annum. Any technology that can assist in the treatment of patients with long-term conditions and reduce the likelihood of complications will provide a considerable opportunity for reducing NHS costs. Additionally, such savings provide a clear opportunity for the private commercialisation of the technology. Furthermore, re-purposing existing drugs would save companies huge resources normally required to bring a new drug to market. Upon the successful completion of the proposed research, the technology could be applied to other poorly-soluble drugs and could also lead to improved sustained drug delivery for a vast range of other diseases, allowing considerable impact across therapeutic healthcare. These economic opportunities will be realised by protecting and exploiting any new intellectual property and building on the applicants' strong track record of previous successful industry collaborations. New start-up companies would attract significant investment to commercialise this technology, creating new jobs and contributing to local wealth creation. For the NHS and other healthcare providers, drug delivery via an injectable, degradable nanocomposite could lead to significant time and cost savings through the reduction in the number of invasive treatments and associated hospital visits.

Society:
An injectable, degradable nanocomposite providing long-acting drug delivery would change clinical practice, it would reduce the burden to the NHS and provide a patient requested alternative to oral administration. In this proposal we aim to develop the technology to deliver drugs to treat five indications; epilepsy, HIV, cardiovascular disease, transplant rejection and diseases of the back of the eye. These diseases effect over 8 million people in the UK. Currently, poor adherence results in patients with increase numbers of complications meaning increased lost work days and the need for greater community support. Ultimately, poor adherence in reduces a patient's healthy lifespan. A long-acting implant would potentially dramatically improve quality of life for patients requiring chronic dosing overcoming poor adherence.
The PDRAs employed on the proposed project will develop a broad range of specialised skills in the fields of polymer chemistry, colloid science, materials science and pharmacology. In addition, all PDRAs will expand on their experience of successfully undertaking multidisciplinary research. Given that all the PDRAs will attend at least two conferences, they will also further develop their presentation skills and obtain networking opportunities through exposure to the UK and international research communities. Working in partnership with clinical academic colleagues will also broaden their experiences of different research environments. They will also undertake outreach activities, including those with potential end-users. Therefore these researchers will be have enhanced employment opportunities at the end of their employment on the project.