Skin Electroporation: Modeling Perspectives - Porous Media: Applications in Biological Systems and Biotechnology - page 343

(a) (b)

Electorode
Gel
Epidermis

r

SC

Dermis

Fat

z

FIGURE 9.4
Electroporation overview: (a) skin fold, (b) close-up of composite representa-
tion of skin electroporation.

electroporation takes place in which nm-sized pores develop within the lipid
bilayer membranes (and under the right conditions, through the corneocytes).
Although this phenomenon has been documented in countless experimental
studies (both in vitro and in vivo ), the exact mechanism behind the sudden
development of these pores is not fully understood. The general theoretical
description of this process has been developed for single lipid bilayers and
is believed to be related to pulse magnitude and lipid-lipid interactions. It
is understood that within an individual lipid bilayer membrane, electropores
are created initially hydrophobic: at this early stage of pore formation the
edges of the pore consist of exposed hydrophobic lipid tails. As the pulse
progresses, the electroporation pore makes a transition to hydrophilic: the
hydrophilic lipid heads position themselves to the edge of the pore (thus cover-
ing the hydrophobic tails). This formation of individual nm-sized hydrophilic
pores within the individual lipid bilayer membrane is electroporation in its
strictest sense. When approaching electroporation of the skin it is impor-
tant to consider that the individual electropores do not cross the entire SC ,
but only single bilayers. The concept of single lipid bilayer electroporation
should be contrasted with skin electroporation. The SC cannot be repre-
sented by a single bilayer because it consists of a lamellar network of lipid
bilayers (about 100) that surround the corneocytes. Thus, for drug molecules
to pass through the SC , they must pass through an electropore in each
of the 100 bilayers. Only small drugs are capable of being transdermally
transmitted through the small, tortuous pathways created during short-pulse
electroporation.
Because the pulse duration is short, there is no significant rise in tem-
perature associated with Joule heating. This means that the SC lipid struc-
ture does not experience a thermal moderate scale fluidization at the mm
scale, although it has been postulated that nm-scale heating contributes to
what is considered to be nonthermal electroporation (Pliquett et al. 2008).
In the following section attention is directed to transdermal transport of larger