Biomedical Engineering Reference
In-Depth Information
[ 206 - 208 ], artificial cells [ 209 ], bioreactors [ 210 , 211 ], and bioimaging tools
[ 212 , 213 ] have been reported.
The most versatile method to prepare such hollow capsules is self-assembly
[ 203 - 205 , 214 , 215 ]. Owing to their amphiphilic nature and molecular geometry,
lipid-based amphiphiles can aggregate into spherical closed bilayer structures in
water: so-called liposomes. It is quite reasonable that the hollow sphere structure of
liposomes makes them suitable as precursors for the preparation of more functional
capsules via modification of the surfaces with polymers and ligand molecules
[ 205 , 216 , 217 ]. Indeed, numerous studies based on liposomes in this context
have been performed [ 205 , 209 , 213 ].
On the other hand, polymer-based amphiphiles, in particular amphiphilic block
copolymers composed of a hydrophobic block and a hydrophilic block with
optimized lengths, can be self-assembled into bilayer structures in aqueous
solution: so-called polymersomes [ 203 ]. Preparation of polymersomes was first
reported by Discher and coworkers in 1999 [ 218 ]. Polymersome preparation is
similar to that of liposomes, usually using a film hydration technique or simple
direct dissolution technique as described in the literatures [ 218 , 219 ]. Since the size
of polymersomes is mainly governed by the volume fraction, which is defined as
the relative hydrodynamic volume ratio of hydrophilic block to the total copolymer
chain, polymersomes can be tuned to sizes ranging from nano- to micrometers
by modifying the polymer structures [ 207 , 220 ]. Compared with liposomes,
polymersomes possess several advantageous properties. The membrane thickness
of polymersomes determines their properties such as elasticity, permeability, and
mechanical stability [ 218 ]. Owing to the higher molecular weight of the polymers
as compared to lipids, the membrane of polymersomes is generally thicker and
tougher, and the membrane makes them more stable and less permeable than
conventional liposomes [ 221 ]. These characteristics enhance the benefit of
polymersomes, especially in drug and gene delivery systems for in vivo use,
because they result in stable blood circulating properties and a decreased rate of
drug release.
Polymersomes can be prepared from various amphiphilic block copolymers,
for example, poly(ethylene glycol)- b -poly(ethyl ethylene) (PEG- b -PEE) [ 218 ],
poly(acrylic acid)- b -polystyrene (PAA- b -PS) [ 222 ], poly(ethylene glycol)- b -poly
(2-vinylpyridine) (PEG- b -P2VP) [ 223 ], poly(glutamic acid)- b -poly(butadiene)
(PGlu- b -PBD) [ 224 ], and poly(ethylene glycol)- b -poly( N -isopropylacrylamide)
(PEG- b -PNIPAAm) [ 225 ]. PEG is a common choice as hydrophilic block of
copolymers that self-assemble into polymersomes, because PEG is noted for its
biocompatibility and resistance to both protein adsorption and cellular adhesion,
resulting in a prolonged blood circulation time for such PEG-based polymersomes.
For therapeutic applications, polymersomes preferably should be biodegradable
as well as biocompatible. Biodegradable polymersomes offer several advantageous
properties compared to nonbiodegradable polymersomes, such as facilitation of
the sustained release of encapsulated molecules and improved safeness through
removal of empty vehicles after the release of drugs. Accordingly, biodegradable
polymersomes have been prepared using block copolymers of PEG as hydrophilic
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