Targeting small molecule drugs to lymph nodes and brain by highly lipophilic prodrugs approach

The main aim of this project is to develop a combined chemistry-based and formulation-based approaches to deliver active therapeutic agents (small immune-oncology compounds) to tumour microenvironment in the brain, and to lymph nodes.

CDT themes

This project aligns with three CDT themes - Predictive Pharmaceutical Sciences, Advanced Product Design, Complex Product Characterisation

Predictive Pharmaceutical Sciences - Development of an improved in silico model for prediction of association of drugs with chylomicrons and the intestinal lymphatic transport

Advanced Product Design - In silico model-assisted design and synthesis of highly lipophilic prodrugs of small molecule immuno-oncology drugs. This will be also combined with design of appropriate lipid-based drug delivery systems for the selected lead candidate prodrugs.

Complex Product Characterisation - In vitro and ex vivo assessment of the synthesized prodrugs for selection of lead candidates for in vivo studies (association with artificial and natural chylomicrons, biorelevant intestinal fluids stability with esterase activity added, lymph/plasma stability. We will also perform in vivo assessment of pharmacokinetics and biodistribution of selected prodrugs and the parent drugs, followed by pharmacokinetic analysis, modelling and simulation.


EPSRC remit

This project fully aligns with EPSRC remit of Transformative Healthcare Technologies

Pharmaceutical technologies underpin healthcare product development. Medicinal products are becoming increasingly complex, and while the next generation of research scientists in the life- and pharmaceutical sciences will require high competency in at least one scientific discipline, they will also need to be trained differently than the current generation. Future research leaders need to be equipped with the skills required to lead innovation and change, and to work in, and connect concepts across diverse scientific disciplines and environments. This CDT will train PhD scientists in cross-disciplinary areas central to the pharmaceutical, healthcare and life sciences sectors, whilst generating impactful research in these fields. The CDT outputs will benefit the pharmaceutical and healthcare sectors and will underpin EPSRC call priorities in the development of low molecular weight molecules and biologics into high value products.

Benefits of cohort research training: The CDT's most direct beneficiaries will be the graduates themselves. They will develop cross-disciplinary scientific knowledge and expertise, and receive comprehensive soft skills training. This will render them highly employable in R&D in the pharmaceutical, healthcare and wider life-sciences sectors, as is evidenced by the employment record in R&D intensive jobs of graduates from our predecessor CDTs. Our students will graduate into a supportive network of alumni, academic, and industrial scientists, aiding them to advance their professional careers.

Benefits to industry: The pharmaceutical sector is a key part of the UK economy, and for its future success and international competitiveness a skilled workforce is needed. In particular, it urgently needs scientists trained to develop medicines from emerging classes of advanced active molecules, which have formulation requirements that are very different from current drugs. The CDT will make a considerable impact by delivering a highly educated and skilled cohort of PhD graduates. Our industrial partners include big pharma, SMEs, CROs, CMOs, CMDOs and start-up incubators, ensuring that CDT training is informed by, and our students exposed to research drivers in, a wide cross-section of industry. Research projects in the CDT will be designed through a collaborative industry-academia innovation process, bringing direct benefits to the companies involved, and will help to accelerate adoption of new science and approaches in the medicines development. Benefit to industry will also be though potential generation of IP-protected inventions in e.g. formulation materials and/or excipients with specific functionalities, new classes of drug carriers/formulations or new in vitro disease models. Both universities have proven track records in IP generation and exploitation. Given the value added by the pharma industry to the UK economy ('development and manufacture of pharmaceuticals', contributes £15.7bn in GVA to the UK economy, and supports ~312,000 jobs), the economic impacts of high-level PhD training in this area are manifest.

Benefits to society: The CDT's research into the development of new medical products will, in the longer term, deliver potent new therapies for patients globally. In particular, the ability to translate new active molecules into medicines will realise their potential to transform patient treatments for a wide spectrum of diseases including those that are increasing in prevalence in our ageing population, such as cardiovascular (e.g. hypertension), oncology (e.g. blood cancers), and central nervous system (e.g. Alzheimer's) disorders. These new medicines will also have major economic benefits to the UK. The CDT will furthermore proactively undertake public engagement activities, and will also work with patient groups both to expose the public to our work and to foster excitement in those studying science at school and inspire the next generation of research scientists.