Integrated radiomaterials chemistry for simultaneous multi-component tracking of nanomedicines in biological matrices

The current global clinical use of nanomedicines benefits patients daily and has considerable market value; global estimates = US$75bn ('11), predicted to be $US160bn by 2015. The decision to develop new nanomedicines balances the needs of patients (are conventional medicinal approaches failing or unable to help?), type of disease/threat to health (is the disease potentially terminal?) and dosing regimes (oral or injectable administration; chronic or acute dosing?). Many therapies require long-term dosing to maintain health over prolonged periods. For example, >33 m people (incl. children) are currently living with HIV/AIDS and the optimised daily dosing (over decades) of highly active antiretroviral therapies helps to prevent progression of HIV to AIDS, and allows a life for many patients that is as close to normal as possible. In contrast, due to the acute nature of cancer (imminent threat to life) short-term interventions, including highly toxic therapies, are required for rapid cure. Cancer research has seen many nanomedicine benefits including the targeting of poorly soluble drugs to solid tumours. Similar contrasts are seen in antiepileptic and cholesterol-lowering therapies (long term health maintenance) versus systemic fungal infections or acute respiratory distress (immediate cure required). Most nanomedicines are enabled by polymer science ranging from polymer-bound drugs through to polymers stabilising drug nanoparticles or forming nanosized drug encapsulants. Nanomedicine expansion to long-term dosage forms and chronic diseases will increase and the behaviour/fate of polymeric materials in the body must be studied to generate safety and toxicology information, to increase the speed-to-clinic (ie patient benefits) and enable decision-making of pharmaceutical companies and regulatory bodies.

Currently, the study of low concentrations of polymeric materials in complex environments is extremely difficult. The use of radioactive isotopes for biomedical research is well established with drugs labelled to allow rapid quantification and tracing, however, very few reports describe radiolabelled polymeric components of candidate nanomedicines and facilities for polymer radiochemistry have largely disappeared in UK Universities. The University of Liverpool has created facilities to enable radiomaterials chemistry, providing new academic UK skills and enabling pharmacological studies of polymers used in nanomedicine strategies and other applications. This 3 year programme aims to conduct the first nanomedicine studies that simultaneously monitor drug AND enabling polymeric materials, whilst exploring the synthesis of radiolabelled polymers with the most up-to-date techniques. This will place UK nanomedicine research at the forefront of understanding and provide an engagement platform for global pharmaceutical companies and regulatory bodies as the huge potential for nanomedicine is realised for patients of all ages across multiple disease areas.

The key focus of the proposal addresses the lack of radiomaterial studies within UK academia and underpins nanomedicine research aimed at improving delivery of new patient benefits.

Whilst new material concepts are developed in global research programmes to enhance drug delivery and action, these materials require BOTH safety and performance studies to ensure they are appropriate and safe for use in new medicines. We aim to engage researchers in the utilisation of radiomaterials approaches to demonstrate the potential patient benefits of their prospective drug delivery methods. Within the field of nanomaterials and nanomedicine, a series of ongoing societal and governmental debates continue to discuss the safety and application of nanoscale technologies. Uniquely, this programme aims to introduce new techniques to facilitate this debate (and future scientific developments) whilst developing a Radiomaterials Laboratory within UK academia that can continue to provide benefits, across multiple scientific activities, for many years after the term of the funding. We will also seek to engage directly with regulatory authorities with clear data that may impact future policies.

The proposal is a collaboration across the sciences of chemistry, nanotechnology, pharmacology and toxicology. It involves a multi-national company keen to invest in the provision of UK academic radiomaterials capabilities, through the recognition that a) the UK is severely lacking in these skills, and b) considerable benefits for universities, industry and the UK economy may be gained by taking a leading position within this science area. This skills gap has been recognised by EPSRC/MRC working groups, citing the need for "multidisciplinary collaboration", highlighting a "shortages of research leaders...in radiochemistry and a need to establish more Principal Investigator level researchers" and stating "radiochemistry research that can develop new chemistry and probes is key".

We aim to advance the understanding of nanomedicines and considerably improve the potential for further development into products and the delivery of future improved patient outcomes. It is hoped that, within 10 years of the start date, the outputs of this research will provide key considerations for global research studies and regulatory bodies when de-risking new nanomedicine candidates.

The beneficiaries of the research therefore are diverse and include scientists, clinicians, general public, patients and industry. It is expected that non-medical disciplines may also benefit strongly (eg engineering/ nanotechnology/data storage/coatings/environmental studies/sustainability) and ongoing research programmes may be enhanced by new understanding. Within our targeted field of nanomedicine, we aim to interact internationally to complement nanomedicine activities focussed on drug delivery benefits and increase the potential for therapy options that will be commercially protected and attractive for industrial exploitation. With the conversion of therapy options into medicines, the potential impact will widen to patients over coming years.

It is important to note that NO NEW DRUGS are being developed but rather the performance and safety of proposed new drug delivery strategies is being studied. If sufficient data can be produced to understand behaviour and direct future research towards fruitful studies, the production of platforms capable of generating benefits across multiple diseases will lead current drugs to better safety profiles and improved performance with the goal of cheaper, more targeted and more appropriate dosing to patients globally.