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Objective: to stay just within the skin’s protective barrier

2015-04-08

RESEARCH. How do you get a substance to penetrate the skin, a substance which can heal and do good? To get it through our barrier against the outside world, but not so far that it is transported away by the blood – enabling it to remain where its effects are needed? This is what Biofilms – Research Center for Biointerfaces at Malmö University is investigating in a new research project funded by the KK Foundation.

Johan Engblom 1The outermost layer of the skin is only ten microns thick and yet it is the main barrier between the body and its surroundings. In total, skin is half a millimetre thick and its most important functions include protecting us against cold and dehydration. But sometimes, for example if we have eczema, we want the skin to absorb a pharmaceutical substance in a cream or ointment we apply to the exact spot we want to treat.
"What we are going to investigate is how to make it easier for the drug molecules to penetrate and then stay in the location where they can be useful", explains Johan Engblom, who is a reader in Pharmaceutical Technology in charge of this research field at Biofilms – Research Center for Biointerfaces.

"The major challenge is to get the substance through the stratum corneum, the outermost layer of the skin which forms blisters when the skin is rubbed sore. It is often said that this layer accounts for approximately 80 per cent of the barrier properties. It consists of dead, flattened cells, whereas the underlying layer consists of living tissue. This is the level at which we want the substance to remain and be absorbed, rather than transported away from the site by the blood to affect the rest of the body", says Johan Engblom.

This is precisely the advantage of allowing drugs to be absorbed through the skin: the parts of the body where the drug is not needed are not involved in the treatment through blood circulation or digestion, which limits the risk of side-effects. The amount of active substance needed is also reduced when the drug is delivered through the skin instead of via the blood.

The project originates from research work conducted by Johan Engblom's doctoral students and postdocs at Malmö University. The project has received SEK 4.8 million from the KK Foundation and partners are pharmaceutical companies Emeriti Pharma, Galenica AB and Bioglan AB. Gothenburg University is also in the group behind the application.

In fact the pharmaceutical substances involved are of secondary importance; the object of the investigation is how molecules with different chemical properties can more easily get to where they are needed.
"We have chosen a fat-soluble and a water-soluble model substance. These molecules can go different ways – it's quite possible that a larger door will be opened for the water-soluble molecule than for the fat-soluble one, or vice versa. Most pharmaceutical molecules have oil properties, i.e. they are fat-soluble, whereas most creams are water-soluble.

Oil and water don't mix. This is central to much of what we do here at the research centre. To simplify somewhat, creams are usually drops of oil in water, together with an emulsifier which makes the consistency smooth. But water drops in oil make the cream more like an ointment. Ointments are stickier and not as manageable as creams. There is more demand for creams. Gels consist largely of water which evaporates on application to the skin. Ointment, cream or gel – often a company can choose to produce a variant of each with the same pharmaceutical substance, in order to cover a larger market segment. We are working with all three variants, but creams are the most common".

Johan Engblom observes that the research network which is now being established in southern Sweden is strong and competitive, and will connect chemistry and medicine more closely. The project has been underway since March and will run for three years. From Malmö University, the participants are Johan Engblom, Tautgirdas Ruzgas, Peter Falkman, Cathrine Albèr and a new postdoc. Further participants are Henri Hansson and Anna Karin Morén from Galenica, Birgitta Svensson and Torbjörn Sund from Bioglan, David Gustafsson and Tomas Fex from Emeriti Pharma, and Marica Ericson from Gothenburg University. The project is expected to generate at least six research publications.

"We have a formalised timetable, but as with all scientific studies, new issues are bound to arise along the way and the lessons we learn from them will obviously affect the paths we choose in the project", says Johan Engblom.

Text: Evelina Mildner Lindén

Last updated by Jerome Nilsson Aja