31. March 2022

The picture of a rat filled with microcontainers wins 1st prize in the DNRF’s Photo Competition 2022

The winner of the first prize in the DNRF’s Photo Competition 2022 is a computed tomography scan of a rat that has been filled with microcontainers loaded with an x-ray contrast agent and then spread out in its digestive system. The picture was taken during a study that examines new types of delivery systems for oral drugs. In this study researchers used little containers on a microscale.

Photo: Rolf Bech Kjeldsen.

There is a play of colors that reveals just enough for the viewer to see a rat’s skeleton filled with tiny microcontainers. The image reminds the viewer of the general complexity of a skeleton’s anatomy while also revealing the amazing beauty one can find with the help of an x-ray image. The winner of the first prize in the DNRF’s Photo Competition 2022 is a computed tomography scan of a rat that has been filled with microcontainers loaded with an x-ray contrast agent and then spread out in its digestive system. The picture was taken during a study at the Center of Excellence IDUN at the Technical University of Denmark (DTU). Over the last 10-15 years the project has examined delivery systems for oral drugs and is currently experimenting with little containers on a microscale.

“The image comes from a study that is about the so-called drug delivery system, which, translated to Danish, is about the delivery of medicine. In our group, we’ve worked with very small devices called microcontainers over the last 15 years. So, it started long before I joined the research group,” said Ph.D. student Rolf Bech Kjeldsen, who took the winning photo.

Small containers on a microscale

The so-called microcontainers are very small containers about the same size as a grain of sugar. The container has an internal cavity that can be filled with different medicine. Once the correct dosage of the medicine has been added to the container, the open upper parts will be sealed with a thin, protective pH-sensitive lid.

“Microcontainers are more or less the same size a sugar grain, so we are speaking about 300-400 µm. You can fill put any medicine in the microcontainer. It could be general medicine, such as a paracetamol, the active drug in pills against headache, or more advanced things, such as vaccines or even insulin,” said Kjeldsen.

When humans take medicine orally, it has to go through the stomach, which is designed to break down many of the key components of a medicine. Therefore, the idea is to get the medicine through the stomach and down to the small intestine, where it will be absorbed into the blood stream and the medicine will have the most effect.

“The thin, pH-sensitive lid protects the medicine, so it gets to the small intestine before the lid starts to dissolve. Then the medicine will be released and absorbed into the blood stream,” said Kjeldsen.

An interest in finding new ways to consume oral medicine has long existed, since this is the kind of dosing that has the best “patient compliance,” a term for how much the patient complies with the treatment. But after Covid-19 interest has greatly increased, since people experienced how time consuming and difficult it was to transport and mass-administer vaccines.

“Even before Covid-19 hit the world, we were working toward developing oral vaccines with the help of microcontainers, but it is clear that interest has grown fast during the pandemic.”

The microcontainers journey through the digestive system

The microcontainers in the image have been filled with an x-ray contrast agent to help improve the understanding of what exactly happens once the microcontainers have been administered orally, and then start to move down the digestive system. The x-ray contrast agent enables researchers to see the microcontainers with the help of a computed tomography scan.

“The image shows how microcontainers act after they have been orally administered and then move down the digestive system and into the small intestine. It is taken with a computed tomography scan, which is a technique we know from hospitals. It is usually used to look at broken bones. We can see all the small red dots, which are the microcontainers with the x-ray contrast agent. If I hadn’t filled the microcontainers with the x-ray contrast agent, they wouldn’t appear on the image, and we wouldn’t be able to identify as well quantify them,” said Kjeldsen.

After the rat was dosed orally with the microcontainers with the x-ray contrast agent, the computed tomography scan images were taken continuously to study the microcontainers’ movement in the digestive system. The winning photo shows the rat five hours after it had been dosed, and you can see that the microcontainers have been evenly distributed in the digestive system.

“Something that we particularly look for is to see if the containers are stuck somewhere or if they move fast and easily in the digestive system.”

Beauty and complexity in one

While the x-ray scanning images are very resourceful and rely on a strong technique, they also have an aesthetic beauty, which the winning photo of the rat shows.

“The image reminds you about the general complexity of skeletal anatomy while it reveals the gorgeous beauty obtainable with x-ray imaging.”

The study with microcontainers in rats is only the first step in a longer project. The research group has moved on to the next step and carried out a preliminary study on rabbits. The next study uses the same principle as with x-ray imaging and has moved on to the processing of the data and images at this stage.

“In regard to how microcontainers act in bigger animals, such as, for example, rabbits, we haven’t yet concluded anything. The two cases with rats and rabbits are very different. Generally, a rat has a much shorter transit time than a rabbit. From the moment a rat eats something until it comes out the other end is relatively short – a few hours. The transit time is longer in rabbits, even longer in pigs, and much, much longer in humans, as we know. It will be exciting to continue on this road when it comes to bigger animals and maybe even people later on,” said Kjeldsen.

Kjeldsen’s time as a Ph.D. student is almost over, but he has received support to continue the research, and going forward, he will have responsibility for the imaging activities in the research group for a period of time.

“Generally, I will have the responsibility for the imaging activities and will continue to look at how the microcontainers act, but I will also look at how we can study and examine without putting the animals down in the end. As mentioned before, we are also working on vaccine delivery, but there is also a big interest in insulin delivery, and I actually think that is where my main focus will be,” said Kjeldsen.

All the studies are being carried out at the Center of Excellence IDUN at DTU.

Raed more about Rolf Bech Kjeldsen and his research here:

Read “X-ray Imaging for Gastrointestinal Tracking of Microscale Oral Drug Delivery Devices” here

Read ”Mikrocontainere: fremtidens vacciner kan være på størrelse med sandkorn” (in Danish) here

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