With nano- and microcapsules, we are able to swallow medication that is usually injected, enabling it to be targeted at a specific body part. But how far have researchers gotten with the development of the new drug delivery solutions, and what are the biggest challenges? Professor Anja Boisen responds to these questions. She is Center Leader of the IDUN basic research centre, which, among other things, develops microcontainers for vaccines, probiotics, and insulin.
Q: Why should we take medication in microcontainers?
A: The capsules protect the medication all the way down past the stomach. When they enter the intestines, they attach to the mucous layer (which protects the intestine, red.) and will therefore stay in one place longer than an ordinary capsule would. Additionally, the containers have only one opening, ensuring a targeted delivery of the content to the intestinal wall, where it is absorbed. This way, the medicine absorption becomes much greater, compared to a capsule that dissolves and releases its contents in all directions. If the medicine is released just 2 mm from the intestinal wall, almost nothing is absorbed and the medicine will be lost. So if these delicate molecules are to stand a chance, they must go through the mucous layer, hit the intestinal wall, attach themselves, and remain attached for a while. And we have discovered some great ideas to pursue relating to this.
Q: What does it take to pursue those ideas?
A: We need different competences and people who can pull together as a unit. What will it look like, and how can we make it as simple as possible to avoid the capsules turning into some kind of monster-sized engineering solution? It may look very good on paper, but it would never be used on a patient. I think there is something elegant in trying to make it as smart and simple as possible. It is mostly about looking at it from a creative angle and being inspired to figure out how to use the knowledge we already have. When IDUN opened, we had a visit from Peter Kurtzhals from Novo Nordisk. He reported that they had a bioavailability of 1 per cent (the proportion of the medicine that the body absorbs, red.) on the oral insulin product they were about to introduce on the market, and he said: “Anja, if you can increase it a few per cent, give me a call.” “OK,” I said, “challenge accepted!” And I think we can. We need some really good data from animals to show that it works. But the signs are promising!
Q: How far along is the development?
A: We can start to test the capsules on large animals at the beginning of next year. It can be a long road from testing to approval, but it is not a new type of medicine we are developing. Rather, it is the method that is new, which will hopefully speed up the approval procedure. It is starting to get really complicated and expensive, but we now know roughly what works and what we believe to be the right direction.
Q: Can microcontainers be used for anything other than medication?
A: Yes, we collaborate with DTU Food on probiotics (live microorganisms that change the intestinal flora, red.). The products currently on the market have a limited effect. Freeze-dried bacteria entering the intestines do ’wake up’, but they will meet an existing bacterial community, which they will need to fight against. Therefore, the vast majority of bacteria do not manage to attach to the mucous layer and multiply. They go right through the intestines or never get a chance to grab hold. If we can find a solution that could ensure that the supplied bacteria colonize the intestine, it could mean much bigger perspectives. It would perhaps become possible to supply bacteria other than those that are super resistant to being freeze-dried.
Q: What are the biggest challenges?
A: The biggest challenge is definitely to get the medication, insulin, or probiotics up close to the cell wall and to make sure that the microcontainers release the content in the right direction—i.e., towards, and not away from, the wall. The next challenge will be to get the microcontainer to attach and release its content in exactly the right spot. It could be in the lower part of the intestines—most probiotics need to travel as far down as possible. If you want to treat an inflamed area locally, the containers should be able to get there on their own—just like applying a plaster to a wound.
Q: Is it not closer to being science fiction?
A: It may well seem like science fiction, but some things just need to be examined, and that is also the point of having an institution like The Danish National Research Foundation, which thinks much further ahead than companies usually do. It is also important that we make mistakes once in a while. For example, after the first animal experiments with the traditional microcontainers and insulin, we had to accept that they do not work. We have to come up with something that can get them closer to the mucous layer. Such periods can be difficult, because you get frustrated. But it triggers a tremendously creative process—and it is important to see any mistakes and failures as an opportunity to start over.