Biomedical Engineering Reference
In-Depth Information
channel proteins into the polymersome membranes (Choi and Montemagno
2005
).
In most applications it is highly desirable to be able to control the release of encap-
sulated substance by triggering a change in membrane properties of polymersomes
via the action of a stimulus. The present chapter focuses on this issue of controlled
release and reviews the most promising approaches to create stimuli-responsive
polymersomes. So far, two strategies have been followed to achieve the controlled
disassembly of polymersomes. The first one exploits the vast possibilities of chemi-
cal synthesis to develop polymer membranes sensitive to the chemical stimuli,
including hydrolysis, oxidation reaction, reduction reaction and pH change. The
second strategy, which also takes advantage of the chemical diversity of polymers,
uses physical stimuli, such as temperature variation, light, magnetic fields, electric
field, osmotic shock or ultrasonic wave, to remotely destroy the polymersomes.
Stimuli-responsive polymersomes are then reviewed in detail according to these
two strategies by dividing the stimuli into chemical and physical stimuli.
2
Polymersomes Responsive to Chemical Stimuli
2.1
Response to Hydrolytic Degradation
Biodegradable polyester-based polymersomes have been made from polyethyle-
neglycol-
b
-polylactic acid (PEG-
b
-PLA) (Ahmed and Discher
2004
), (Meng et al.
2003
), polyethyleneglycol-
b
-polycaprolactone (PEG-
b
-PCL) (Ghoroghchian et al.
2006
), and polyethyleneglycol-
b
-poly(g-methyl-e-caprolactone) (PEG-
b
-PMCL)
(Zupancich et al.
2006
). Under physiological conditions (pH = 7.4), these polyesters
degrade by hydrolysis. However, polyester hydrolysis is accelerated by low pH,
which may be useful given the acidic environment in tumors and endolysosomes.
To provide controllable degradation and adjustable release times ranging from
hours to weeks, polymersomes were formed by blending PEG-
b
-PLA and PEG-
b
-
PCL with inert PEO-
b
-PBD (Ahmed and Discher
2004
). These polymersomes were
loaded with two anticancer drugs. Doxorubicin (water soluble) was loaded in the
aqueous interior of the polymersomes while paclitaxel (water insoluble) was
included in the hydrophobic layer of the membrane. The loaded polymersomes
were degraded in vivo and drug release occurred with a time scale of a day. This
degradation and release was shown to be coupled with the phase transition behav-
iour of the block copolymer amphiphiles (see Fig.
1
). Polyester hydrolysis occurs
preferentially at the chain end, thereby increasing the hydrophilic/hydrophobic
ratio of PEG-polyester chains and preferred curvature of the self-assembly. If we
discuss with the packing parameter
p,
the hydrophobic chain shortening induces a
decrease of
p
value from 1 to 1/2 to 1/3. The comparatively short hydrophobic
blocks of the degraded chains are unstable in a bilayer. Instead, they tend to segre-
gate, congregate, and ultimately induce hydrophilic (i.e., PEG-lined) pores and
eventually the vesicular carriers disintegrate into mixed micellar assemblies. These
polymersomes are a promising method for multi-drug delivery.
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