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

聚合物纳米粒具有高负载性、生物相容性和生物降解性，在制药工业中被用作药物输送应用的载体。这类系统已经证明，在提高治疗效果的同时，有效地将活性成分转移到目标部位；聚合物和药物之间的相互作用是这些纳米颗粒设计的关键。然而，为了更好地理解药物-聚合物相互作用的类型和影响，以及提取这些信息的最佳程序，还需要进一步的工作。因此，本项目的目标是评估非破坏性和非侵入性的太赫兹时域光谱(THz-TDS)作为测量药物-聚合物相互作用的工具，以优化聚合物纳米颗粒的设计。太赫兹辐射通常从100 GHz到10太赫兹，位于电磁光谱的红外和微波区域之间。分子间和分子内的键相互作用、振动和旋转都发生在这个频率范围内；因此，突出了这一技术的潜力，为药物-聚合物系统中涉及的分子运动和动力学提供了重要的洞察。从根本上说，该项目的结果取决于三个关键目标：通过文献回顾和实验工作了解基本原理，配制聚合物纳米颗粒，并对设计的聚合物纳米颗粒进行评估。对于分析和表征，THz-TDS-如上所述-将以可重复的方式与互补的结晶学技术相结合使用。拟议的调查与EPSRC的“传感器和仪器”和“化学生物学和生物化学”的研究领域相一致，并构成了学术和社会价值，以及在制药行业的实际重要性。首先，通过适当的工作和出版物，该项目将加强对围绕药物-聚合物相互作用的基本原则的理解，并帮助解决现有文献中的论述或分歧。此外，通过提高对基本原理的理解，这项研究在工业规模上的实际意义是重大的。对配方的必要和不必要的组成部分有一个更好的想法，将加快开发过程，并通过更早地认识到什么是可行的和不可行的来节省成本。进一步探索相互作用的影响，研究新的组合，使引入新药-以及那些以前失败的试验阶段-进入应用的可能性增加。因此，对社会的好处包括以更负担得起的价格提供更多的药品和治疗更广泛的疾病。该项目由阿斯利康的合作者资助，并将与阿斯利康的合作者共同实施。

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.