287045 Effect of Stretching On Transport Across the Stratum Corneum

Wednesday, October 31, 2012
Hall B (Convention Center )
Monica Hwang, Annie Jensen, Kristina Runas, Bruce Yan, Olivia Warren and Nancy K. Lape, Engineering, Harvey Mudd College, Claremont, CA

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 Ecorneocyte >> ESC, 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.


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