Self-Assembled Nanoreactors - Cluster for Molecular Chemistry

1466 Chemical Reviews, 2005, Vol. 105, No. 4 Vriezema et al.
Figure 18. Electron micrographs of various types of morphologies formed by aggregated block copolymers. (a) Micelles
and (b) micellar rods from polystyrene-b-poly(acrylic acid) (Reproduced with permission from ref 203. Copyright 1999
National Research Council of Canada), (c) vesicles from poly(ethylene oxide)-b-polyethylethylene (Reproduced with
permission from ref 204. Copyright 1999 American Association for the Advancement of Science), (d) lamellae from
polystyrene-b-poly(phenylquinoline) (Reproduced with permission from ref 207. Copyright 1998 American Association for
the Advancement of Science), (e) branched wormlike micelles from poly(ethylene oxide)-b-polybutadiene (Reproduced with
permission from ref 206. Copyright 2003 American Association for the Advancement of Science), and (f) left-hand helices
from polystyrene-b-poly(L-isocyanoalanyl-L-alanine). (Reproduced with permission from ref 205. Copyright 1998 American
Association for the Advancement of Science.)
referred to as polymersomes. Since the first reports,
208,209 a large number of examples describing the
formation of polymersomes have been published. 210-213
The structure of vesicle-forming block copolymers can
vary from simple coil-coil diblock copolymers and
further to rod-coil diblock copolymers to coil-coil
and rod-coil multiblock copolymers with and without
additional cross-linkable groups (Figure 19).
The advantage of polymersomes over liposomes is
their increased stability and the rigidity of their
membrane system, which contribute to their increased
lifetime. The vast amount of available monomers
and the ability to vary the ratio of the two
blocks make it possible to tune the properties of the
resulting vesicles, for example, vesicle size, polarity,
stability, toxicity, etc. In general, however, the permeability
of the membranes of block copolymer
vesicles is reduced because their thicknesses are
higher and their membranes have less fluidic character
as compared to liposomes. 211
In the group of Discher, much effort has been put
into establishing the physicochemical properties of
polymersomes based on poly(ethylene oxide)-b-polybutadiene
(PEO-PBD) and poly(ethylene oxide)-bpolyethylethylene
(PEO-PEE). 204,214-216 As a first step
toward in vivo applications, encapsulation experiments
were performed with the proteins myoglobin,
hemoglobin, and albumin (Figure 20).
The encapsulation of these proteins was rather
straightforward, viz., adding the solid block copolymer
to an aqueous solution of the desired solute and
waiting for 24 h. The encapsulation efficiencies for
the different proteins, however, varied. 217 The polymersomes
appeared to be stable in blood plasma and
were observed to be inert to white blood cells and
cultured cells. In vivo studies performed with these
polymersomes in rats showed that their in vivo
circulation times were about 2 times longer than
“PEGylated” stealth liposomes (20-30 h in rats). 218
These circulation times turned out to be primarily
dependent on the PEO block length, rather than on
the hydrophobic core-forming block. These experiments
clearly show that these PEO-based diblock
copolymers have great potential as drug delivery
vehicles.
For the controlled release of encapsulated solutes,
much effort is being focused on the development of
stimuli-responsive vesicles, that is, capsules that are
disrupted by changes in their environment. Such a
system based on polymersomes was prepared by
encapsulating the enzyme glucose oxidase (GOx)
within polymersomes of poly(ethylene glycol)-b-poly-
(propylene sulfide)-b-poly(ethylene glycol) (PEG-PPS-
PEG) (Figure 21). 219
The thioethers in the hydrophobic middle block are
converted to more hydrophilic sulfoxides and sulfones
upon exposure to an oxidative environment, in that
way increasing the hydrophilicity and solubility of
the macromolecular amphiphile. GOx converts glucose
to gluconolactone, and, in the presence of oxygen,
hydrogen peroxide is formed. It was shown that
destabilization of the GOx-encapsulating polymersomes
occurred upon the oxidative action of the
formed hydrogen peroxide when glucose was extra-