Stimuli-Responsive Polymersomes - Intracellular Delivery: Fundamentals and Applications - page 321

3.4 Responses to Electric Field, Osmotic Shock

and Ultrasonic Wave

The effects of electric field on giant polymersomes of PEO- b -PBD (Aranda-
Espinoza et al. 2001 ; Bermudez et al. 2003 ) and on giant liposomes (Vlahovska
et al. 2009 ; Riske and Dimova 2005, 2006 ; Dimova et al. 2007 ) have been studied
by the group of Discher and by the group of Dimova, respectively. The stimulation
by an electric field is not specific to a given amphiphile. The response of the
vesicles to the electric field and the destruction of the membrane are due to an
increase tension of the vesicle directly induced by the electric field. The hydropho-
bic core of the membrane thickness d and dielectric constant e (low compared to
that of the aqueous environment) behaves as a capacitance C (typically in the order
of mF.cm −2 ). The charging time for the membrane depends on the environmental
conductivity inside and outside the vesicle, and typically takes the order of a frac-
tion of ms in saline solution. Consequently, if the pulse duration supply is larger
than the charging time of the capacitance, the transmembrane potential V thus
generated can be considered constant and only dependent on the applied electric
field E, the radius R of the vesicle and the angle q between the field direction and
the normal to the membrane: V = REcos(q). This potential creates an electro-
compressive stress perpendicular to the plane of the membrane s = 1/2CV 2 . The
increase in electric field applied resulting in a net increase in tension of the mem-
brane. There is a threshold electric potential for which the vesicle tension reaches
its lysis value and consequently the vesicle disintegrates. This experiment is illus-
trated in Fig. 22 . In practice, the critical transmembrane potential is of order of
V c = 1-10 V. The critical constraints are then in the order of s c = 10 (liposomes) to
30 (polymersomes) pN.nm -1 . Nevertheless, it should be noticed that the magnitude
of the electric field necessary to achieve polymersome lysis is kV/cm. Apply these
fields through the human body for drug delivery would be likely accompanied by
severe side effects.
The responsive polymersomes to osmotic shock has been reported by the group
of Weitz (Shum et al. 2008 ). Polymersomes encapsulating 1-hydroxypyrene-3,6,8-
trisulfonate sodium (HPTS) were produced from PEG- b -PLA block copolymer
using microfluidic fabrication. Although the membrane is impermeable to the small
HPTS salts, water molecules can diffuse in and out of the polymersomes. The
osmotic pressure, p osm , is related to the concentration of solutes,

π= cRT

osm

where c is the molar concentration of the solutes, R is the gas constant and T is the
temperature. Due to osmotic pressure difference, water diffuses from regions with
a low salt concentration to regions with a higher concentration. Osmotic pressure
can therefore be used to tune the sizes of the polymersomes. If the osmotic pressure
change is sudden and large, the resulting shock can break the polymersomes. The
kinetics of the polymersomes' response following a large osmotic shock is too fast
to visualize; the process is therefore slowed down for visualization by gradually