Biomedical Engineering Reference
In-Depth Information
The distributive function is based on the exponential form (Tezel et al.
2003)
γ ( r P )= χ exp
ςr P
(9.19)
The constants χ and ς may be derived from singular experiment, for exam-
ple, the values of these constants as measured for pig SC are given as
follows: χ =0 . 024; ς =0 . 00045 (Tezel et al. 2003). The distributive func-
tion is ex pli citly defined as the normalized distributive function in which
χ =2 2 π ; ς =2 σ 2 , where σ is the standard deviation, whose value is also
determined experimentally (Kushner et al. 2007b).
The methods that rely on nondestructive transport (low voltage electrically
assisted and pure diffusion) are successful only for small molecular transport.
To transport larger drugs into the skin, researchers have focused on altering
the barrier function of the SC . To facilitate transdermal transport of “large
molecule,” the barrier structure of the SC and the lamellar lipid bilayers
must be altered. In the following section a method called electroporation,
which relies on electrical and thermal destruction of the SC barrier function,
is introduced.
9.6 Skin Electroporation
Skin electroporation is an approach used to enhance localized transdermal
transport in which the skin is exposed to a series of electric pulses (Regnier
et al. 1999; Denet et al. 2004). Typically, in skin electroporation a section of
skin coated with an applicator gel is pinched between two electrodes, which
deliver the electric pulses to the skin (see Figure 9.4[a]). Electroporation of the
SC barrier dramatically increases the permeability and electrical conductivity
of the SC by creating microscopic pores through which agents are able to
pass through the outer barrier (Pliquett et al. 1995; Prausnitz 1996; Vanbever
and Preat 1999; Pliquett and Gusbeth 2000). Electroporation pulses can be
classified in one of the two regimes: short pulse and long pulse, and because
the physical effects of the two regimes differ greatly, the choice of which regime
to use is dependant largely on the drug size (Denet et al. 2004).
9.6.1 Short Pulse (Nonthermal)
Small molecules require lower permeability increases, and once this minimum
SC permeability is met, solutes of low molecular weight can access deeper
skin layers purely by diffusion. Electroporation pulse times that are classi-
fied as short duration are typically
100
µ
s . In this regime nonthermal skin
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