Localized Transport Regions in Human Skin, unconstrained (left) and constrained (right)
Rapid, controlled molecular transport across human skin is of great
interest for transdermal drug delivery and non-invasive chemical sensing.
The main barrier is the stratum corneum (SC), which can be described by
a ``brick wall'' model in which the dead, hydrated corneocytes are the
bricks, and the surrounding multilamellar lipid bilayer membranes are
the mortar. Small lipid-soluble molecules can partition into the SC,
and then diffuse across the lipid bilayer membranes, but water soluble
molecules, particularly charged molecules, cannot penetrate significantly
by this route.
Our general hypothesis is that high voltage (HV) pulsing
(Uskin > 50V) creates aqueous pathways (``pores'') through
stratum corneum (SC) lipid bilayer membranes,
a more specific hypothesis is that short pathway segments
are formed across 5--6 lipid bilayer membranes
which connect adjacent corneocyte interiors
forming transcellular straight-through pathways.
Moderate voltage (MV) (Uskin = 5 to 50V)
pulses appear to electroporate cell linings of the appendages.
Our overall aim continues to be understanding of
the mechanism of electrical creation of pathways,
and the associated ionic and molecular transport.
Previous work shows that pulsing causes large and rapid
increases in the flux of charged molecules across human skin.
The basic idea is to permeabilize the SC (reversibly or
irreversibly, under control), to provide major improvements
in transdermal drug delivery and the possibility of better
minimally-invasive sampling of subcutaneous fluid
analytes (e.g. glucose).