(593ao) Effect of Stretching On Transport Across the Stratum Corneum

EFFECT OF STRETCHING
ON TRANSPORT ACROSS THE STRATUM CORNEUM

M. Hwang, A. Jensen, K. Runas, B. Yan, O. Warren, N.K. Lape

Harvey
Mudd College, 301 Platt Blvd., Claremont, CA 91711

The SC consists of layers corneocytes, often
considered impermeable, imbedded in an intercellular lipid bilayer matrix which
is considered the main diffusion pathway for molecule transport through the SC.
Young's Modulus (E; a measure of stiffness) for the SC is reported to be 420kPa¹,whereas
for an isolated corneocyte, E was found
to be 450MPa². Given that E_corneocyte >> E_SC, it is likely that the lipids will expand more than
the corneocytes under applied strain. An extension of the SC is therefore
hypothesized to increase the lateral surface area of the lipid bilayer. This
indicates that the application of uniaxial strain should increase permeability
and thus drug transport through the SC.

To investigate this
effect, a stretching device was designed and implemented to apply constant
strain to a test site on the ventral side of a human forearm. The stretching
mechanism consisted of two tabs holding 3M healthcare tape attached to the
subject's arm; the tabs pull outwards from the test site. The position of the
tabs was controlled by an Arduino Decimilia,
which operated two GWS S03N STD Servo motors. An in vivo tape stripping study was performed on n=20 participants to
analyze the effect of drug transport on stretched skin compared to
non-stretched skin. 40% strain was applied to the test site on the subject's
right forearm. The left forearm was used as an un-stretched control site. A
saturated Methylparaben (MPB) solution was placed on the test site for 1 hr.
The site was then tape stripped 10 times. The amount of SC per tape strip was
determined using a SquameScan850. Capillary electrophoresis was used to
quantify the amount of MPB on each tape strip. An in vivo trans epidermal water loss (TEWL) study was performed,
using a Delfin? Vapometer (n=7) and a BioX? Aquaflux system (n=3) to
determine the difference in water flux out of the skin between stretched (40%
strain) and un-stretched skin.

        The cumulative amount of MPB was plotted
against the cumulative amount of SC removed for the control and stretched sites
of each participant. Slopes of this data indicate the MPB permeation rate. The
ratio between the slopes of the stretched to control site were calculated for
each participant (Figure 1) as a measure of the change in permeability. A
permeability ratio that is greater than one (red line in Figure 1) indicates a
higher permeation rate for the stretched skin. The ratio of the TEWL
measurements between stretched and un-stretched skin are shown in Figure 2. The
results indicate that the effect of mechanical stretching generally causes a
decrease in both MPB transport and TEWL.

The
current data in both studies does not account for the change in surface area
between stretched and un-stretched skin. When skin is stretched the skin's
natural folding decreases, causing the area of application to decrease. This
reduction of area in contact with MPB during the tape stripping experiments
could reduce the amount of relative transport. Using PRIMOS imaging equipment
the surface profile was obtained in vivo
using the stretching device for both stretched (40% strain) and un-stretched
skin. A polynomial fit will be used to determine the change in surface area. This
correction will be applied to MPB and TEWL to confirm or reject the original
hypothesis.

Acknowledgements

The
authors are grateful for financial support from the Patton and Claire Lewis Fellowship
in Professional Practice, The Howard Hughes Medical Institute (HHMI), and
Johnson & Johnson, as well as assistance from Russell Walters (Johnson
& Johnson), Catherine Mack Correa (Johnson & Johnson), and Paul Stovall
(Harvey Mudd College).

References

1.    Agache
PG, Monneur C, Leveque JL, De Rigal
J.  1980. Mechanical Properties and
Young's Modulus of Human Skin in Vivo. Archives of Dermatological Research. 269: 221-232.

2.    Leveque JL, Poelman MC, De Rigal J, Kilgman AM. 1998. Are Corneocytes Elastic? Dermatology. 176: 65-69.