Stimuli-Responsive Polymersomes - Intracellular Delivery: Fundamentals and Applications - page 303

insoluble above pH 7. In the cross-linked hydrophobic membranes of polymer-
somes, a decrease in solution pH protonates the DEA residues which causes in turn
the membrane swelling and the permeability increasing.

2.4.2 pH Responsive Polymersomes Formed from Peptide-Based

Polymersomes

Polypeptides are a special class of building blocks for vesicle-forming amphiphilic
block copolymers because of their stimuli-responsiveness (to pH or temperature),
secondary structures, functionalities, and biocompatibility (Schlaad 2006 ), (Carlsen
and Lecommandoux 2009 ). Nevertheless, there are only a limited number of
examples of polymersomes made from polypeptide-containing block copolymers
and these examples can be divided into two main families. The first family is com-
posed of hybrid block copolymers, where the polypeptide is the hydrophilic block
and a classical synthetic polymer, such as polybutadiene (PBD) or polyisoprene
(PI), is the hydrophobic block. The second family includes co-polypeptides in
which both the hydrophilic and hydrophobic blocks are polypeptides. Polymersomes
formed by hybrid block copolymers with a polypeptide as the hydrophobic block
and a synthetic polymer as the hydrophilic one have not yet been reported.
Polymersomes have been formed in aqueous solutions using polybutadiene- b -
poly(L-glutamic acid) (PBD- b -PGlu, 17-54 mol% glutamate) (Kukula et al. 2002 ;
Checot et al. 2002, 2005 ), polybutadiene- b -poly(L-lysine) (PBD 165 - b -PLys 88 and
PBD 107 - b -PLys 27 ) (Sigel et al. 2007 ; Gebhardt et al. 2008 ) and polyisoprene- b -
poly(L-lysine). In these systems, a change in pH or temperature can induce a change
in the secondary structure of the hydrophilic polypeptide corona (charged coil,
a-helix or b-sheet). The secondary structure of poly(L-glutamic acid) (a polypeptide
with -COOH side groups) changes from a charged coil at high pH (pH > 6) to an
a-helix at low pH (pH < 5), while that of poly(L-lysine) (a polypeptide with -NH 2
side groups) changes from an a-helix at high pH (pH = 11) to a charged coil at low
pH (pH = 6). It has been reported that the transition from a charged coil to a a-helix
conformation in the hydrophilic corona did not change the morphology of the poly-
mersomes, but did cause a large decrease in their size (hydrodynamic radius, by
20-50%). Savin's group has also reported that in basic conditions (pH = 10.9), a
temperature increase induced a transition from an a-helix to a b-sheet conformation
in the poly(L-lysine) corona of polymersomes made from PBD 107 - b -PLys 27 (Gebhardt
et al. 2008 ). Consequently, the hydrodynamic radius of the polymersomes increased
by a factor of two (from 70 nm to 140 nm) when the temperature was raised from
40°C to 63°C. This block copolymer is a good example of a dual-responsive system
sensitive to both pH and temperature changes.
Similar pH and temperature dual-responsive polymersomes were also formed
from a series of triblock ABA copolypeptides (poly(L-lysine)- b -poly(g-benzyl-L-
glutamate)- b -poly(L-lysine) (PLys- b -PBGlu- b -PLys)) in which the block ratios
ranged widely (Iatrou et al. 2007 ). For example, the hydrodynamic radius of poly-
mersomes made by PLys 134 - b -PBGlu 64 - b -PLys 134 was of 129 nm at pH = 7.4 and
T = 25°C (PLys in charged coil); this value decreased to 92.5 nm at pH = 11.7 and