Growing the guts to improve drug uptake testing
Dr Martin Garnett and his team at the University of Nottingham have made a substantial contribution to making studies of drug uptake across the gut lining more accurate and realistic than existing animal and human cell models.
How does the research help humans?
To ensure new medicines are safe, it is important to measure how they get into the body. The main route to drug uptake in humans is a layer of cells in the gut known as the epithelium. Drugs are therefore routinely tested to see how well they are transported across the gut epithelium into the body. There are also concerns about the safety of various nanoparticles produced in today’s society. This research can also be applied to test whether, how, and in what quantities nanoparticles can get into the body.
Why did we fund this human-relevant animal-free research?
The currently available cellular models are too simple to determine drug and nanoparticle uptake across the epithelium accurately, so animal experiments are still widely used. The Nottingham research team aimed to produce a much more realistic cell culture model of drug uptake across the gut epithelium, to replace these experiments.
How many animals are typically used in this type of research?
In 2011 there were 57,624 mammalian experiments in the UK associated with ‘alimentary studies’ mainly using mice and rats. A subset of these experiments would have been associated with drug testing, although the pharmaceutical industry also carries out many animal experiments abroad for cost and regulatory reasons. The issue of how reliable and realistic the cellular models are will affect the number of animal experiments carried out.
How are the animals used?
The pharmaceutical industry still uses a wide range of models to predict oral uptake of drugs under development. These range from in vitro cell assays, assays on excised animal tissue and chronic experiments in surgically modified dogs.
This research produced a much more realistic cell culture model of drug uptake than any other animal or human cell study. The team developed a human cell model by growing gut cells on a basement membrane; this avoided using animal serum routinely used in cell culture and grew more realistic looking human epithelium. The resulting cell model also solved a known problem occurring in other cell studies, where cells stick together too tightly and so don’t allow some drugs to squeeze through. By solving this problem, the team could demonstrate reproducible permeability of their model, which is important for future validation of the method.
This research provides a more realistic model for drug transport and toxicology studies that, once complete, could be used to replace animal studies. Dr Garnett adds, “We have made a number of key steps towards the objective of reducing animal experiments and have a better understanding of what still needs to be done to reach our goal”. The team now want to focus on adding another cell type to their model that will produce a mucus layer, to make it even more lifelike.