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

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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.