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

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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