Personalised Pulsatile Materials (PPM)

The project aims to develop a ground-breaking class of materials: functional porous polymers able to expand and collapse their volume fully autonomously in a predesigned rhythm for a predesigned duration. The goal of this fellowship is to produce biocompatible rhythmic (pulsatile) materials for medical applications. In particular, for controlled/targeted drug delivery in chronopharmacotherapy to treat diseases with established oscillatory rhythms in their pathogenesis, e.g. arthritis (10 million people in UK), duodenal ulcers (1 in 10 people in UK), cancer (1 in 4 of all deaths in UK) and cardiovascular diseases (1 in 4 adults in UK). Also, for mechanoresponsive tissues (e.g. bone and the vascular system) in regenerative medicine to facilitate cell activity and the assembly of mechanically robust and biologically functional tissue (organs). The proposed methodology incorporates collaboration with BDD (http://www.bddpharma.com/) and internationally recognised academic partners. This will enhance progress, knowledge dissemination, mitigate risks and ensure the materials are suitable for end-user driven development of fit-for-purpose products, and will accelerate transfer of research outcomes to healthcare applications. The proposal is built on the ground-breaking discovery of chemical oscillators employing polymeric substrates (Chem Commun 2014) and in-depth studies of biocompatible intelligent hydrogels (Adv Mater Sci Eng 2015) resulting from CAF2009. The project duration is 2 years and the methodology has 3 work packages (WP). WP1 in collaboration with Professor Vancso's group, Twente University, addresses the synthesis and experimental validation of proof-of-principle autonomous polymeric materials. In WP2, in collaboration with BDD company, characterisation and validation of the materials is pursued to meet end-user needs and regulatory requirements. WP3 in collaboration with Professor Kolar-Anic's group, Belgrade University, focuses on the development of predictive physico-chemical models to aid experimental studies and facilitate the design of patient-tailored materials. The proposal is aligned with Healthcare Technologies Grand Challenges (Developing Future Therapies; Optimising Treatment) and Advanced Materials and Future Manufacturing Technologies areas of research.

The proposed research is pioneering. Developing a new class of intelligent materials, namely rhythmic (pulsatile, oscillatory) materials, whilst academically significant, has the strong potential for applications leading to societal and economic gain worldwide. Oscillatory chemical reactions employing polymeric substrates are currently unique to the Novakovic research group and taking them from discovery to applications is timely and momentous. The outcome of the proposed research will open a new chapter in the area of nonlinear dynamics in chemical systems and offer new directions in materials science, pharmacotherapy and tissue engineering.

In the area of drug delivery a successful outcome will offer truly personalised, drug delivery on demand. The economic impact of a successful research outcome is enormous. Active Pharmaceutical Ingredients (API) are the core of drug manufacturing. The price of APIs is the main cost driver for manufacturing. Only a limited number of pharmaceutical companies have their own API manufacturing capabilities, and none of them can make all required APIs in-house. Technology that leads to the reduction of the amount of API needed in medication while increasing its efficiency guarantees a large economic effect.

The technological solutions proposed here have the strong potential to improve the quality of life for a large number of people and, importantly, enable solutions previously not possible. Proposed rhythmic materials would lead to reduced side effects of the drug delivered and offer truly personalised treatment regimes. An aging population can significantly benefit from reliable hands-free drug delivery technology that would further result in far less reliance on hospital care. This is of direct relevance to Government as it directly leads to reducing costs to the NHS due to less wastage and further reduced costs by lessening patient reliance on hospitals.

User engagement is strongly exercised in the research methodology by close collaboration with Bio-Images Drug Delivery (BDD) a specialist drug formulation company with keen interest in controlled drug delivery. BDD has extensive knowledge of the relevant areas in the field of pharmacotherapy, will take an active role in the proposed research and is perfectly positioned to move from the research project outcome to full application and full release of impact. While the research proposed is pre-clinical BDD is a key link to fast and meaningful development in line with current regulatory requirements and enhanced technology transfer. To secure knowledgeable engagement in addition to a first-hand understanding of the pharmaceutical industry and related processes, Novakovic will train in the area of Health Economics and GLP.

Academic project partners are in place (the Vancso Materials Science and Technology of Polymers research group, Netherlands and the Kolar-Anic Non-linear Dynamics research group, Serbia) to aid project progress and promptly take research outcomes to new directions increasing impact further. To aid worldwide academic impact prospective project outcomes have been discussed with other academic leads keen to "take up" and further accelerate the research outcomes (Arthritis Centre UK, Newcastle section - rhythmic materials as scaffolds for mechanoresponsive tissue; Kuksenok group, Clemson University - computational design of rhythmic materials).

To create long-lasting academic capability a strong accent is placed on training skilled researchers and staff from the Novakovic, Vancso and Kolar-Anic groups in this multidisciplinary area so all three groups gain capabilities previously not available to them.

As the development of novel medical methods and technologies is relevant to the whole of society, engagement and communication with the general public will be pursued and executed (talking to patient groups via Wellcome Trust, public lectures, media).