2000
A
dry stream
QS 405-32-1
membrane deposition
∆fn (Hz)
0
∆f3
∆f5
∆f3 (fit)
∆f5 (fit)
-2000
USING THE QCM-D TECHNOLOGY TO CHARACTERIZE
-4000
MEMBRANE WATER PERMEABILITY
120
wet stream
dry stream
B
Transport of water molecules through cell membranes
is) crucial for many vital functions in living organisms. The human
∆D (x10
∆D (x10 )
80
body consists of ca. 70% water, which needs to be∆Dtransported
to tear ducts, saliva glands, kidneys, brain, lungs and
(x10 )(fit)
∆D (x10 )(fit)
blood, etc. Additionally, the outermost layer of the skin regulates hydration by modulating the uptake and release of
40
water. Methods for studying such processes are therefore relevant for skin related cosmetics, pharmacy and many
other medical applications. In this work the QCM-D technology was successfully applied to such studies.
-6
∆Dn (x10-6)
3
-6
5
-6
3
-6
5
0
0
INTRODUCTION
The outermost layer of the skin, the
skin in order to regulate the hydration
and prevent dehydration. Additionally,
it protects the underlying tissue from
Thickness
∆f3
∆f5
0.760
-4500
0.750
is roughly 10-40 µm thick and under
2000
lipid composition is highly relevant for
400
t(s)
dry stream
450
skin related pharmaceutics and cos-
(mass uptake), ∆f, and energy dissipation (viscoelasticity), ∆D, the mem-
membrane deposition
brane thickness could be determined
using the Voigt viscoelastic model in
∆f5
∆f3 (fit)
∆f5 (fit)
QTools (Figure 1).
wet stream
dry stream
When the humidity over the lipid mem-
-4000
brane is increased water vapor diffus120
toxicity of different compounds. Model
es into the lipid molecules and causes
B
membranes with different lipid compo-
swelling. This process results in a
∆Dn (x10-6)
∆D3 (x10-6)
APPROACH AND EXPERIMENTAL
SETUP
∆D5 (x10-6)
∆D3 (x10-6)(fit)
∆D5 (x10-6)(fit)
80
decrease in ∆f (mass increase) and
increase in ∆D (softer film). From the
swelling characteristics it was possi-
40
ble to extract physical properties such
as solubility, S, and diffusivity, D, of
0
In the work reviewed in this application
0
200
400
the water molecules in the membrane
600
(Figure 1). The water permeability, P,
note, a Q-Sense E4 instrument has
humidity could be controlled with high
precision using a moisture exchanger.
The model SC membranes consisted of
ceramides, free fatty acids and cholesterol in different compositions. These
of the membrane, i.e. at which rate wa-
0.770
Figure 1.C(A) The thicknesses of the membrane
-4000
during increased humidity asThickness
calculated using
∆f3
the
Voigt
model
in
QTools.
Displayed
is also the
0.760
∆f5
∆f response relative to the uncoated sensor. (B)
-4500
The frequency change ∆f and (C) the dissipa0.750
tion change ∆D for the uncoated sensor and the
sensor coated with a lipid membrane in a dry
0.740
and a humid stream respectively. The 3rd-5000
and
the 300
5th overtones
shown. 450
350 are400
500
t(s)
ter molecules are able to permeate, is
∆fn (Hz)
connected to the flow chambers and the
Thickness (µm)
been used and run in a well-controlled
gas environment. Nitrogen gas was
urements under identical conditions
tive changes in resonance frequency
metics, and also for understanding the
sitions are often used in such studies.
baseline could be established. Meas-
ing of the membrane. From the rela-
500
∆f3
-2000
uncoated sensor in dry nitrogen gas, a
were performed after an ex-situ coat-
0
∆fn (Hz)
water uptake processes as related to
350
A
extended immersion in water its increased hydration is revealed by the
several micrometers. By analyzing an
-5000
300
ternal factors. Normally the SC layer
from a few hundred nanometers up to
-4000
0.740
infection and damage caused by ex-
wrinkling of the skin. Understanding
600
∆fn (Hz)
for water transport into and out of the
400
C
0.770
Thickness (µm)
Stratum Corneum (SC), is responsible
200
proportional to the product of S and D.
RESULTS AND DISCUSSION
Different parameters were varied in order to determine their impact on S, D
and thereby P. First the thickness of the
were applied to the sensor surface
tightly-packed and homogenous lipid
SC membrane was varied, with a con-
(Au) using an airbrush, thereby forming
membranes with thicknesses ranging
stant composition, as shown in Figure 2.
QS 405-32-1
A
the membrane surface is the limiting
20
factor, rather than the diffusion laterally
15
in the membrane.
1
Additionally, the effect of the free fatty
0.1
P (Barrer)
P (Barrer)
10
acid chain length was investigated.
1.0
2.0
3.0
Thickness (µm)
on the other hand, increased with the
chain length; as a result of these off-
B
setting trends in S and D, P remained
1
constant. When comparing saturated
clear that P in the former case is signif-
0.1
icantly lower (Figure 3). This is due to
more order in the lipid membrane likely
0.01
0.0
1.0
2.0
3.0
Thickness (µm)
S(cm3 STP)/(cm3 cmHg)
100
C
leading to a higher resistance against
penetrating water molecules.
This effect is utilized in cosmetics and
Saturated FFA
dition of unsaturated free fatty acids
increases the water permeability of the
1
skin and therefore benefits moisturizer
performance. Model membranes can
m1 m2
Linoleic
Oleic Petroselinic
FFA mixture Unsaturated FFA
B
4
2
10
8
C 14 16 18 20 22 23 24
Saturated FFA
m1 m2
Linoleic
Oleic Petroselinic
FFA mixture Unsaturated FFA
C
6
4
2
0
C 14 16 18 20 22 23 24
Saturated FFA
skin related pharmaceutics. The ad-
10
0.1
0.0
C 14 16 18 20 22 23 24
8
0
and unsaturated free fatty acids it is
S(cm3 STP)/(cm3 cmHg)
D (10-10 cm2/s)
10
decrease in S could be observed. D,
5
8
bicity with increased chain length, a
D (10-10 cm2/s)
0.01
0.0
10
0
Due to a slight increase in hydropho-
A
m1 m2
Linoleic
Oleic Petroselinic
FFA mixture Unsaturated FFA
Figure 3. (A) The water permeability, P, (B) diffusivity, D, and solubility, S, for the model SC
membrane with varying lipid chain length and
saturation.
be customized on a molecular level
1.0
2.0
Thickness (µm)
3.0
Figure 2. (A) The water permeability, P, (B) diffusivity, D, and solubility, S, for the model SC
membrane plotted as a function of membrane
thickness. All other parameters were kept constant.
in order to optimize factors affecting
the membrane permeability on a very
ACKNOWLEDGEMENTS
detailed level.
We would like to thank Professor Daeyeon Lee at the University of Pennsylvania for kindly providing valuable input.
CONCLUSIONS
The effect of membrane composition
on water permeability in SC was
REFERENCES
D strongly increased with the mem-
successfully studied using QCM-D.
[1] Myung Han Lee, Bomyi Lim, Jin
brane thickness whereas the effect on
Based on the swelling characteris-
Woong Kim, Eun Jung An and Daeyeon
S was less pronounced. As an over-
tics, which were sampled through
Lee. Effect of composition on water per-
all effect P increased with increased
the changes in resonance frequency
meability of model stratum corneum lipid
membrane thickness. This is to be ex-
and energy dissipation, the diffusiv-
membranes. Soft Matter, 2012, 8, 1539-
pected since it is well known that the
ity and solubility of water molecules
1546.
diffusion of water molecules normal to
in the membrane was calculated. The
permeability is directly proportional
to the product of these two factors.
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