Unique holistic approach to cyclodextrin research at Aalborg University

Unique holistic approach to cyclodextrin research at Aalborg University

Cyclodextrins are created when starch polymers are degraded by enzymes and turned into miniscule rings of glucose that resemble a cup. These cups, which in themselves are soluble in water, are capable of containing either H2O or other molecules – even whole molecules or parts of molecules that are not otherwise soluble in water.

- “One of the key properties of cyclodextrins is their ability to form complexes with a variety of substances when dissolved in water. This ability can be used in a wide range of contexts because it enables the dissolution of otherwise hydrophobic molecules or substances in water. But it also means that if you dissolve cyclodextrins in water, they can ‘catch’ other molecules that you want removed from the water – for instance if you want to purify the water – or you can convert liquids into dry or crystallized forms that emerge when they form inclusion complexes with the cyclodextrins” Kim Lambertsen Larsen explains.

FOCUSING ON BOTH BASIC RESEARCH AND PRACTICAL USE

When Kim Lambertsen Larsen started working at Aalborg University in 1994, the work in the research unit primarily focused on what he calls the science of cyclodextrins: Figuring out how these glucose rings are created, and what their properties are. Now, however, the scope is much wider and contains both the chemistry behind the cyclodextrins and their practical application as a technology in industry. This comprehensive approach is unique for the research group in Aalborg, as other researchers usually only look at one aspect of these tiny starch polymers:

“You could say that we work with every aspect of the cyclodextrins, from studying how they interact with water on a molecular level or how they behave when in crystal structures to looking at how we can turn these properties into a technology that can be used in medicine, in weight-loss, in cleaning products and so on” 

This thorough research into a wide range of properties and applications of cyclodextrins is in part facilitated by Aalborg University’s problem-based learning model where groups of students can aid the researchers in their work. “The chance to have students working on this with us gives us the opportunity to try out a wider range of things than if we ourselves were to perform all the experiments. We can ask the students, “We have this idea, will you test it in a project?” And that will give us an indication of whether or not to pursue that line of thinking – and that path of research” Kim Lambertsen Larsen says.

CYCLODEXTRINS IMPROVE THE EFFECT OF MEDICINE

One field that has a long history of utilizing the properties of cyclodextrins is medicine. Here, the cyclodextrins are used as an inert excipient facilitating efficient delivery of drugs, but recently also as a medicine in themselves.

- “When we get medicine in tablet form, these are swallowed and will dissolve in the stomach and digestive system. The speed with which the medicine is absorbed in the colon depends on the speed with which the tablet dissolves. First the solid tablet needs to disintegrate into small crystals of the medicine, and then these crystals need to dissolve so that the medicine can be absorbed by the body. The dissolution of the medicine in crystalline form and the intrinsic solubility of the medicine is usually fairly low, which are the main reasons that some medicines have poor bioavailabilities” Kim Lambertsen Larsen explains. If, however, cyclodextrins are added to the mix that makes up the tablet, the medicine will form complexes with them, and the dissolution rate of the tablet will increase markedly.

“This enables us to absorb the medicine faster and more efficient because the medicine dissolves more quickly in our digestive system or even in a glass of water before we take it – think, for instance, of the way TREO or Panodil Zapp works” Kim Lambertsen Larsen adds.

The faster dissolution of the tablets increases the concentration of medicine in the colon, which again increases the speed with which the medicine is absorbed through the colon membrane and into the bloodstream – and as such the speed with which it takes effect.

FROM EXCIPIENT TO ACTUAL MEDICINE

In recent years, the use of cyclodextrins in medicine has been extended to utilizing their ability to bind other molecules for medicinal purposes: “Cyclodextrins have proved to be very, very good at binding cholesterol. This means that it is now possible to remove cholesterol by injecting cyclodextrins straight into the brain of a patient suffering from Niemann-Pick type C disease and improve that patient’s cholesterol balance. Even more, recent studies have shown that cyclodextrins may be used for the treatment of atherosclerosis, the most common cardiovascular disease and one of the most common causes of death worldwide. Here, the cyclodextrins simply dissolve the cholesterol crystals and reduce the atherosclerotic plaques” Kim Lambertsen Larsen explains and adds:

- “In addition, they are now used as an antidote to counteract the effects of certain types of muscle relaxants that are used during surgeries or endoscopies where the patient needs to have a tube down his or her throat. Earlier, the after effects of the muscle relaxant would last for maybe half an hour, but now the patient gets an injection of cyclodextrins tailored to the removal of this specific medicine from the bloodstream, and the recovery period is down to two minutes.”

INVENTING NEW USES OF CYCLODEXTRINS

The use of cyclodextrins has also moved into a variety of other industrial fields. One of the most well-known examples is the odor remover Febreze that utilizes cyclodextrins for binding the molecules that make clothes or dog baskets smell unpleasantly. Kim Lambertsen Larsen has, together with former students, invented a new way of applying cyclodextrins’ properties: Using cyclodextrins as coating for surfaces which can then be used to either absorb or release molecules to the surroundings. The technology is currently on the verge of being commercialized.

“During my work with the cyclodextrins, I got this idea that maybe we could trick the cyclodextrins into attaching themselves to a surface through placing them in a water-ethanol solution – in other words, create a type of coating that will enable us to place their complex-forming properties on a specific surface. We tested the idea in our laboratories and got very good results” Kim Lambertsen Larsen explains and adds: “Now, imagine using this on filters where we utilize the ability of cyclodextrins to form complexes with medicines for removing medicinal residues from our wastewater before sending it back into the water cycle. Or, the other way around: If we want to release a scent from, say, a fabric, we can coat that fabric with a layer of cyclodextrins and deposit the scent in them. The scent will then be released slowly and potentially only under certain conditions such as a specific level of heat and humidity – such as when we sweat or just wear the clothing.”

The researchers are currently working with a major German company concerning the use of the coating technology at a major scale.

“This is one of those instances when you get the chance to go all the way from basic research to applied technology. You have an idea, you go into the lab to test it, and you make it work. It will be amazing if we can make it fly commercially and see it brought into use in other contexts to solve challenges in society”