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NC3Rs: National Centre for the Replacement Refinement & Reduction of Animals in Research
Project grant

Defining drug delivery into and across the oral mucosa using a tissue engineering and mathematical modelling approach

Portrait of Professor Craig Murdoch

At a glance

In progress
Award date
December 2021 - March 2024
Grant amount
£430,354
Principal investigator
Professor Craig Murdoch
Institute
University of Sheffield

R

  • Replacement
Read the abstract
View the grant profile on GtR

Contents

Overview

Why did we fund this project?

This award aims to develop the first mathematical models of oral mucosal drug delivery to replace in vivo drug delivery optimisation studies.

Most drugs are administered through ingestible tablets or by injection. These delivery routes have a number of drawbacks, including degradation by liver enzymes before the drug reaches the bloodstream and patient discomfort or anxiety due to needles. There is increasing interest in delivering drugs through the oral mucosa both to treat oral disease and as an alternative to tablets and injections. This has led to a rise in the number of in vivo studies using a range of species, including rodents and rabbits, but pigs are often used as their oral mucosa is most similar to humans in terms of structure, morphology, and permeability characteristics. Depending on the study, repeat blood sampling or whole-body imaging under anesthesia may be used to determine drug delivery success whereas topical applications typically require tissue to be excised.

Professor Craig Murdoch will use data from human tissue to create an in silico model of the oral mucosa. This model will incorporate key biological and physical mechanisms, including discrete cells and multiple penetration pathways (trans- and para-cellular). The in silico model will then be used to optimise various points of drug delivery including how long the drug stays in the mucosal tissue, how quickly it enters the bloodstream, and any differences between healthy and diseased tissue.