Skin Electroporation: Modeling Perspectives - Porous Media: Applications in Biological Systems and Biotechnology - page 344

molecules by longer pulses that have been associated with large temperature
rises.

9.6.2 Long Pulse (Thermal)
For larger molecule transport, longer duration pulses (up to several hundred
ms) are required. Longer pulses make possible two important secondary effects:
electrophoresis and Joule heating.
Electrophoresis is the electric-field-induced motion of charged particles
through a solution. Even with increased permeation of the SC , larger molecules
experience greater viscous resistance to transport through the tortuous SC .
Because simple diffusion is not adequate to overcome this barrier, the electric
field provides the force to overcome resistive viscous forces and drive the large
charged molecule through the layers of the SC . Thus, longer pulsing times are
used to increase the distance that the electrophoretic forces move the solute.
Also important to skin permeation studies are the Joule-heating-induced
local temperature rises. It is understood that the effects of long duration skin
electroporation pulses ( > 25 ms) are Joule heating and the resulting localized
temperature rises, which result in thermotropic phase transitions within the
lipid bilayer matrix of the SC (Denet et al. 2004). At temperatures around
70 ◦ C the barrier function of the SC is dramatically reduced (Golden et al.
1987; Potts and Francoeur 1990) because the SC lipid lamellar structure expe-
riences a fluidizing phase transition (Golden et al. 1987; Cornwell et al. 1996;
Al-Saidan et al. 1998). It is recognized that localized Joule heating associ-
ated with electroporation contributes to increased permeability of the SC by
lipid chain melting (Pliquett et al. 1998, 2005; Vanbever et al. 1999; Denet
et al. 2004). The temperature rises are proportional to Joule heating, Q J , and
pulsing times, τ P , by the relation

τ P Q J
ρC p

∆ T ∝ (9.20)

m- to
mm-sized regions of increased permeability. Early researchers of skin electro-
poration have used the phrase LTR to describe these concentrated electrically
induced regions of increased permeability (Pliquett et al. 1996, 1998). The
development of LTRs is always associated with thermal effects (Pliquett et al.
2008), and it is stressed that this increase in permeability due to Joule heating
should not be mistaken for pure electroporation (which does not require large-
scale temperature rises.) To the reader unfamiliar with skin electroporation,
the distinction between short- and long-pulse electroporation is stressed; the
reader must also recognize the distinction between the nonthermal primary
nm-sized pores that occur within a single bilayer and the

The thermal alterations associated with these longer pulses result in µ

m- to mm-sized
LTRs that pass through the entire SC and are associated with Joule heating.
Also the reader should not confuse the term SC thermal LTR formation with
actual macroscopic voids within the skin. This type of electroporation of the

µ