Researchers develop technology to help medicines reach the right place in the body

Every second of every day, the human body works to protect its organs and vital functions from external threats. Cells carefully control what is allowed to pass through their membranes, while the blood-brain barrier prevents harmful substances from reaching the brain.

Without these gatekeeping mechanisms, the body could not function. Yet from a drug development perspective, researchers sometimes wish they were a little less strict.

If selected substances could be allowed through, it would become easier for medicines to reach the places where they can do their job.

Professor Carsten Uhd Nielsen, Department of Physics, Chemistry and Pharmacy, explains:

“Of course we don't want all kinds of harmful substances entering our brains and cells, so these defence mechanisms are essential. But if we can develop a technology that allows selected compounds to get through, it could help patients recover from disease or at least help them feel better while they are living with a disease.”

The gatekeeping role is carried out by so-called transport proteins, which are found in every cell. Their job is to stop unknown or unwanted substances from entering. Among these proteins are the P-glycoproteins, known as P-gp, which are the focus of Carsten Uhd Nielsen's innovation project, supported by DKK 894.000 from the the Innovation Fund at the Faculty of Science.

SDU has filed a patent application

His team aims to develop compounds that can attach themselves to the transport proteins and temporarily prevent them from blocking selected active drug ingredients. The goal is to test the compounds in rats and demonstrate that they work, providing the foundation for eventually moving towards clinical trials in humans.

“This has evolved from an academic research project into an innovation project. It would be exciting if some of the younger researchers involved eventually had the opportunity to take it further through a spin-out company,” says Carsten Uhd Nielsen.

In addition to Carsten Uhd Nielsen, the team includes Assistant Professor Laust Moesgaard, Postdoctoral Researcher Konrad Pakula, Laboratory Technician Maria Pedersen and Professor Jacob Kongsted. Bachelor's and master's students are also involved in the project. The project has received proof-of-concept funding from SDU RIO, and SDU has filed a patent application based on the discoveries made so far.

This innovation project is a team effort

“For me, it is important that this is a genuine team effort. We all share ownership of the project, and we're doing it because we enjoy it. Having students involved matters too. Innovation gives them a different perspective and shows them that it is not enough for an idea to work on paper. It has to work in cells and animals. Otherwise, it is never going to work in humans,” says Carsten Uhd Nielsen.

The potential of blocking transport proteins is significant and extends to several areas of medicine, including cancer treatment. P-gp proteins play an important role here because cancer cells exposed to chemotherapy often increase their production of these proteins, making them even better at protecting themselves from the active compounds used in treatment. As a result, chemotherapy drugs may become less effective, or in some cases stop working altogether.

P-gp proteins are also highly active in the intestine, where they can prevent active drug ingredients from being absorbed into the bloodstream. The same blocking mechanism is found in the blood-brain barrier.

Vast databases and virtual compounds

“The blood-brain barrier is there to protect the brain from everything circulating in our bloodstream. That protection is absolutely essential. At the same time, it is becoming increasingly important to deliver compounds into the brain because people are living longer and face a greater risk of diseases that require diagnosis or treatment in the brain. This is another area where we would like to be able to block P-gp,” explains Carsten Uhd Nielsen.

So where do researchers find compounds capable of blocking P-gp and allowing carefully selected medicines to pass through?

The days when medicinal chemists relied primarily on trial and error in the laboratory are long gone. Today, much of the work involves exploring vast databases and using virtual compounds. Researchers design and evaluate promising molecules on a computer before ordering them from specialised manufacturers that produce compounds on demand. If the results continue to look promising, the next step is to test them in animals.