A
research team at Karolinska Institutet in Sweden has succeeded in
describing the structure and function of the outermost layer of the
skin—the stratum corneum—at a molecular level. This opens the way not
only for the large-scale delivery of drugs via the skin, but also for a
deeper understanding of skin diseases.
“You
could say that we’ve solved the puzzle of the skin barrier, something
that has great potential significance for dermatology,” says principal
investigator Dr. Lars Norlén, associate professor at Karolinska
Institutet’s Dermatology and Venereology Unit.
The
upper layer of the skin is a watertight barrier called the stratum
corneum. A research group at Karolinska Institutet have now structure
determined this barrier layer at a molecular level, unlocking the
secrets of the skin’s perviousness. This will hopefully enable the
widespread administration of drugs though the skin instead of via pills
or injections, which brings several advantages; for example, it means
that drugs can be delivered evenly over time instead of in doses, and
patients bypass the first-passage metabolism, whereby the entire dose
passes the liver, thus increasing the risk of adverse effects.
“We
can now construct computer simulations to help us find out which
substances have to be added to different drugs to open up the skin,”
says Norlén. “We hope to one day be able to administer regular drugs
like insulin and antibiotics this way.”
To
conduct their study, the researchers developed an entirely new
experimental approach involving rapidly freezing tiny skin samples and
studying them under a low-temperature electron microscope.
“This
has given us an unprecedented opportunity to determine the molecular
structure and function of native cells and tissues in situ without
having our data muddied by the addition of dyes, solvents or plastics,”
adds Norlén.
Their
discovery has profound significance for dermatology. The majority of
skin diseases manifest themselves in some kind of functional disorder of
the skin’s protective barrier, and the researchers now want to use
their method to determine such changes at a molecular level. If they
succeed in this, it will be a decisive step towards a deeper
understanding of these diseases and, hopefully, the development of new,
improved treatments.
“This
may be a breakthrough for dermatology,” says Norlén. “Our team has
devoted the past 20 years to unlocking the mysteries of the stratum
corneum.”
All
land-living organisms are surrounded by a protective watertight shell.
In humans and other vertebrates, it comprises a uniquely complex layer
of fat between the cells of the stratum corneum.
“Understanding
how this protective barrier has developed is an important step towards
explaining why life on land exists and is even possible,” says Norlén.
Publication:
The Human Skin Barrier is Organized as Stacked Bilayers of
Fully-extended Ceramides With Cholesterol Molecules Associated With the
Ceramide Sphingoid Moiety
Source: Karolinska Institutet
