Skin Electroporation: Modeling Perspectives - Porous Media: Applications in Biological Systems and Biotechnology - page 345

skin provides a measure of disruption of the SC architecture (the lamellar
lipid sheets), and it is this disruption that allows for increased permeability.
These disruptions do not generally occur homogenously throughout the skin,
but at localized spots. Skin electroporation causes local regions of high per-
meability on a membrane that in its unperturbed state acts as a barrier. To
reiterate: skin electroporation does not create large voids through the SC , but
local regions of high permeability.

9.6.3 LTR: Experimental Observation
Experimentally it has been shown that in some cases the high-temperature
contours associated with Joule heating may originate near skin appendages
(sweat glands or hair follicles) and as the pulse is applied the LTRs propa-
gate (spread) radially outward along the SC (Pliquett and Gusbeth 2000).
Figure 9.5 depicts a close-up of the SC near a preexisting pore. As the lipid-
phase transition temperatures are attained and move radially outward, the
lipid sheets become fluidized as in the lower panel of Figure 9.5. Depending on
pulse intensity, the scale of the distances covered by these high-temperature
fronts is on the order of 100

m occurring on a timescale of 10-100 msec
(Vanbever et al. 1999). As this heat front moves through the SC , it supplies
the energy to activate lipid-phase transitions. Thus the lipid-phase transition
(barrier function breakdown) can be thought of as a propagating heat front
through the SC . Adding support to this idea are the results of in vitro studies
in which it is shown that within the front the electrical and mass perme-
abilities may be many orders of magnitude higher than outside of this front
(Vanbever et al. 1999; Pliquett and Gusbeth 2004).
Direct evidence of the localized moving heat front and localized regions
of transport is not available in vivo (within living tissue) studies, although
remarkable findings are given from in vitro studies that are conducted in
which human SC is removed and electroporated under observation (Pliquett
et al. 1995, 2005; Prausnitz 1996; Vanbever and Preat 1999; Vanbever et al.
1999; Pliquett and Gusbeth 2000, 2004). Using fluorescence microscopy and
time-resolved freeze fracture electron microscopy during applied pulses of 80 V
at various durations, structural changes occurring within the SC (human and
porcine) are found as a result of localized Joule heating, and it is shown that
these structural changes are highly localized, taking up less than 1% of the
skin's surface area (Pliquett et al. 2005). A fluorescence microscope matched to
a very sensitive camera is used to capture the progression of the growing heat
front associated with Joule heating (Pliquett and Gusbeth 2000). For pulses
shorter than 1 msec, Joule heating is negligible; however, when pulses of 200 V
intensity and 200 msec length are used, striking thermal phenomena are cap-
tured. In fact, in that study, the moving thermal front is captured in a series
of microscopic photographs at 40, 80, 160, and 240 msec by tracking isotherms
of 40 ◦ C and 60 ◦ C that grow radially outward from a point of origin. By 240
msec the front diameter has grown to 0.4 mm. A comparison between local

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