Drug risk assessment and repurposing using biomimetic chromatography and body-on-chip technology

Drug discovery pipelines can be lengthy, expensive and prone to a high degree of attrition with few drug candidates successfully reaching the market. Animal testing has been amply used to select lead drug candidates for first-in-Man clinical studies.

Although the use of animals can be useful to assess drug distribution, metabolism and therapeutic effects, species differences versus humans often decrease the translational success rate of a new drug. Moreover, the use of animals at early stages of drug screening or during repurposing exercises can be expensive, can be impractical when handling large libraries of prospective drug candidates and can have low scientific value at the cost of a high number of animals used. Therefore, there is a need to design more efficient drug discovery pipelines and to increase confidence on selection of the lead compounds at early stages of the process.

This project will investigate the use of biomimetic chromatography as a fast, economic and high-throughput platform to screen and rank compounds' physicochemical properties, drug interaction with silence sites, and binding to human plasma proteins. In this project we will couple biomimetic chromatography with a modified body-on-chip technology to screen compounds' affinity to different human cell targets (to aid drug risk assessment and repurposing exercises), characterise multi-organ biodistribution and metabolism, and predict drug success in humans. Validation of the new methodology will be done by comparing it with gold-standard in vivo outcome measurements of the same drugs already tested in humans using micro-dosing Positron Emission Tomography (PET) imaging.

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PhD Studentship

Status

Active

Institution

University of Edinburgh

Co-Investigator

Dr Mark MacAskill; Dr Patrick Hadoke

Grant reference number

NC/V001302/1

Award date

Jan 2021 - Nov 2023

Grant amount

£90,000 (Joint award with Unilever)