Temperature-dependent Terahertz Time-Domain Spectroscopy as a Tool to Measure Drug-Polymer Interactions in Polymeric Nanoparticles

Polymeric nanoparticles are implemented as carriers in the pharmaceutical industry for drug delivery applications due to their high loading capability, biocompatibility and biodegradability. Such systems have demonstrated effective transport of the active ingredient to target sites at improved therapeutic efficacy; with the interaction between polymer and drug key to the design of these nanoparticles. Further work, however, is necessary for an improved understanding of the types and influences of drug-polymer interactions, as well as the optimum procedure to extract this information.

Consequently, the aim of this project is to assess the non-destructive and non-invasive terahertz timedomain spectroscopy (THz-TDS) as a tool to measure drug-polymer interactions, in order to optimise the design of polymeric nanoparticles. Typically ranging from 100 GHz to 10 THz, terahertz radiation lies between the infrared and microwave regions of the electromagnetic spectrum. Both intermolecular and intramolecular bond interactions, vibrations and rotations occur in this frequency range; thus, highlighting the potential of this technique to provide crucial insight into the molecular motions and dynamics involved in drug-polymer systems.

Fundamentally, the outcome of the project is dependent on three key objectives: to develop an understanding of the underlying principles through literature review and experimental work, to formulate a polymeric nanoparticle and to evaluate the designed polymeric nanoparticle. For analysis and characterisation, THz-TDS - as already stated - will be used in combination with complementary crystallography techniques in a reproducible manner.

The proposed investigation aligns to EPSRC's 'Sensors and Instrumentation' and 'Chemical Biology and Biological Chemistry' research areas and constitutes academic and societal worth, as well as practical importance in the pharmaceutical industry. Firstly, through appropriate work and publications, the project would enhance understanding of the fundamental principles surrounding drug-polymer interactions and aid in tackling existing discourse or disagreements in literature.

Moreover, by improving understanding of the fundamentals, the practical implications of the research on an industrial scale are significant. A greater idea of the necessary and unnecessary components for formulation would speed up development processes and save costs through an earlier appreciation of what would and wouldn't work. Further exploring the influence of interactions and investigating novel combinations brings the possibility of introducing new medicines - as well those previously failing trial phases - into application. Thus, the benefits to society include enhanced availability of drugs and the treatment of a wider range of diseases, at more affordable prices.

The project is funded by and will be carried out in conjunction with collaborators at AstraZeneca.

The primary outputs from the CDT will be cohorts of highly qualified, interdisciplinary postgraduates who are experts in a wide range of sensing activities. They will benefit from a world leading training experience that recognises sensor research as an academic discipline in its own right. The students will be taught in all aspects of Sensor Technologies, ranging from the physical and chemical principles of sensing, to sensor design, data capture and processing, all the way to applications and opportunities for commercialisation, with a strong focus in entrepreneurship, technology translation and responsible leadership. Students will learn in extensive team and cohort engaging activities, and have access to cutting-edge expertise and infrastructure. 90 academics from 15 different departments participate in the programme and more than 40 industrial partners are actively involved in delivering research and business leadership training, offering perspectives for impact and translation and opportunities for internships and secondments. End users associated with the CDT will benefit from the availability of outstanding, highly qualified and motivated PhD students, access to shared infrastructure, and a huge range of academic and industrial contacts.

Immediate beneficiaries of our CDT will be our core industrial consortium partners (MedImmune, Alphasense, Fluidic Analytics, ioLight, NokiaBell, Cambridge Display Technologies, Teraview, Zimmer and Peacock, Panaxium, Silicon Microgravity, etc., see various LoS) who incorporate our cross-leverage funding model into their corporate research strategies. Small companies and start-ups particularly benefit from the flexibility of the partnerships we can offer. We will engage through weekly industry seminars and monthly Sensor Cafés, where SME employees can interact directly with the CDT students and PIs, provide training in topical areas, and, in turn, gain themselves access to CDT infrastructure and training. Ideas can be rapidly tested through industrially focused miniprojects and promising leads developed into funded PhD programmes, for which leveraged funding is available through the CDT.

Government departments and large research initiatives are formally connected to the CDT, including the Department for the Environment, Food and Rural Affairs (DEFRA); the Cambridge Centre for Smart Infrastructure and Construction (CSIC); the Centre for Global Equality (CGE); the National Physics Laboratory (NPL); the British Antarctic Survey (BAS), who all push our CDT to generate impacts that are in the public interest and relevant for a healthy and sustainable future society. With their input, we will tackle projects on assisted living technologies for the ageing population, diagnostics of environmental toxins in the developing world, and sensor technologies that help replace the use of animals in research. Developing countries will benefit through our emphasis on open technologies / open innovation and our exploration of responsible, ethical, and transparent business models. In the UK, our CDT will engage directly with the public sector and national policy makers and regulators (DEFRA, and the National Health Service - NHS) and, with their input, students are trained on impact and technology translation, ethics, and regulatory frameworks.