Electroporation nanocarriers containing insulin resulted in fourfold


In contrast to iontophoresis, electroporation uses
high voltage pulses for short duration to create localized aqueous permeable
regions in between lipid membranes by destabilization. Usually square waves or
exponential voltage pulses are used for the period of 10ms-500ms where create
transmembrane potential of 1 ekV in SC layer of the skin.  This method is shown to be more effective as
compared to iontophoresis for several drug molecules in vitro. However there
are not much data about in vivo studies and its clinical importance is still to
be tested.Rastogi
et al. (2010) studied the transdermal delivery of insulin using electroporation
and it was reported that insulin flux increases linearly when voltage is
linearly increased.  Polymeric
nanocarriers containing insulin resulted in fourfold increase of insulin
deposition in rat skin when compared with solution and the insulin’s
therapeutic levels were maintained upto 36 hours.Sonophoresis

In sonophoresis, ultrasound of frequency
higher than 20 kHz is used to create destabilization of the membrane. In TDDS,
ultrasound in low frequency region of 20 kHz to 10MHz with intensities up to 3
W/cm2 is gaining importance to enhance the drug delivery.  Park et al suggested those low frequency
ultrasounds (i.e. ~20 kHz) are 1000 fold better in inducing greater perturbation
of the skin (Park EJ, Werner J, Smith
NB (2007) Ultrasound mediated transdermal insulin delivery in pigs using
a lightweight transducer. Pharm Res 2007
Jul;24(7):1396-401).  Sonophoresis
induces thermal, chemical and mechanical chances in skin tissues which lead to
enhanced drug delivery. During sonophoresis different things happen like pore
size increases due to increase in skin temperature which further causes
alteration in SC lipid bilayer as well as cavitation is also caused due to
formation of gas pockets within the cell. However thermal and cavitation are
the most significant mechanisms by which sonophoresis drives the drugs into our
system . When ultrasonic waves pass through a medium, wave pressure amplitude drops
with the distance and this attenuation is caused either by absorption by the
medium or scattering effect. When ultrasonic waves are absorbed, they cause
increase in medium temperature by transforming ultrasonic energy into heat,
however this temperature increase depends on the frequency, intensity and
exposure time .  But Aldwaikat et al. (2013) reported that in case
of metronidazole diffusion, thermal
effect promoted the reverse diffusion of the drug. Therefore it is contemplated that permeation ehnacement due to
ultrasound might be due to cavitation mechanism