Researchers at the University of Nottingham in the UK are launching a study aimed at developing a more “realistic”, cell-based model of drug uptake that could serve as a reliable alternative to animal testing.

The three-year project has funding of £152,780 from the Dr Hadwen Trust for Humane Research, the UK-based charity that promotes the development of alternatives to animal studies in biomedical investigations.

A team led by Dr Martin Garnett, Associate Professor in the University’s School of Pharmacy, wants to develop an improved cell-based model for determining how easily drugs and nanoparticles enter the body through the gut.

Epithelial basis

Existing cell models for studying drug uptake across the gut are based on epithelial tissues, which constitute one of the main barriers to uptake, the researchers note.

In these studies, epithelial cells are grown on a porous artificial membrane, or substrate, that allows scientists to measure the passage of drugs and other molecules across the cells.

However, this substrate has been found to prevent the movement of some larger molecules and particles, the researchers point out.

In the new study, therefore, the substrate will be replaced by an innovative new support made from woven nanofibres. This was developed by Professor Bob Stevens from the School of Science and Technology at Nottingham Trent University.

Basement membrane

An important part of the project will be building on the Nottingham team’s previous findings related to the basement membrane, the thin layer of fibres underlying the epithelium. This component is present in the normal human gut but missing from conventional cell models.

The previous research, which was also funded by the Dr Hadwen Trust, showed that the basement membrane “is important for both the normal growth of epithelial cells and as a barrier to uptake of some molecules and nanoparticles”, Dr Garnett explained.

“In our new work we will extend these findings to produce a more realistic model.”

Transporter cells

Mucus produced by some cells in the epithelium can affect how quickly drugs pass into the gut, while so-called M cells (microfold epithelial cells) have been found to help transport some nanoparticles.

Both of these cell types will be incorporated into the new model in an effort to improve its accuracy.

Hopefully the end result will be “a comprehensive and accurate model for studying uptake of all drugs and nanoparticles”, the Nottingham researchers said. 

“This will have the potential to reduce the need for animal studies in both the pharmaceutical industry and for toxicology studies on nanoparticles.”