Biomedical Engineering Reference
In-Depth Information
Electroporation is still in the experimental stage, and many researchers have
employed model nontherapeutic molecules to demonstrate the feasibility of its use.
More biotechnologic and therapeutically derived molecules have now been investigated
for transdermal delivery, including heparin
[14]
, oligonucleotides
[15]
, and genes
[16]
.
The main hurdle to electroporation is its further development for practical applications.
Mechanism of Electrical Methods
Electroporation involves the application of high-
voltage pulses for a very short duration. The pulses are thought to produce transient
aqueous pores in the lipid bilayers of the SC, which may be seen as a localized area
capable of drug transport called the localized transport region (LTR). These openings
provide momentary pathways for drug diffusion all the way through the horny layer
[17-19]
. The technique of electroporation is more typically applied to the unilamellar
phospholipid bilayers of cell membranes. The feasibility of electorporation for trans-
dermal drug delivery was first demonstrated by Prausnitz et al.
[14,18]
. The electri-
cal behavior of the human epidermal membrane (HEM) as a function of the scale and
period of the applied voltage mimics closely the breakdown and recovery of bilayer
membranes seen during electroporation. In contrast to iontophoresis, electroporation
acts mainly on the skin, with less effect by electromigration due to the short pulse
“on” time. The SC requires approximately 1V pulse per bilayer, and 100 multilamel-
lar bilayers require 100V pulses for electroporation
[18,19]
. As with iontophoretic
and electroporative transport, some studies have indicated that high-voltage pulse-
induced transdermal delivery of charged or even neutral drugs could be controlled
by the proper use of electric considerations, that is, pulse voltage, width, and number
[20-22]
. Although it is generally believed that electroporation involves the creation
of aqueous pathways (pores) in the SC, to some extent this theory is controversial
[23]
. These proposed channels have not yet been identified in any microscopic study,
which may be due to their small size (about 10 nm), sparse distribution (0.1% of
the total skin area), and ephemeral nature (millisecond to second). Electroporation
results in the breakdown of lipid bilayers, hydration of skin, and decreased resis-
tance of skin. Existing successful
in vitro
studies should be supplemented with
in vivo
studies for a step toward the development of the electroporation system
[24,25]
.
Notably, during electroporation highly localized pockets of molecular transport
are observed, revealed by real-time video imaging for fluorescent molecules called
as LTR
[17]
. The mechanism that explains the perturbation of the lipid barrier of the
horny layer during electroporation is a heat dissipation phenomenon. Considering
three compartment models in skin, it was observed that localized areas with large
micropore is generated
[26]
. Although it was stated to be a nonthermal process, the
temperature rose after electric pulses of 100V (transmembrane voltage) applied for
1 ms. A “pore” is supposed to form very rapidly, preceding any potential tempera-
ture rise. However, localized heating may also occur at sites of large current den-
sity, especially with extended pulses. Even though convection spreads the heat front
across the skin, the Joule heating could be sufficient for the melting of skin lipids
with phase transitions around 70°C, which suggests that the temperature augmenta-
tion plays an important role. The transport of water-soluble molecules was observed
to be facilitated by the electric field due to the electrophoretic impetus in conjunction
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