copolymers with shorter PMPC blocks (10 or 20) had DNA binding affinities
comparable to PDMAEMA homopolymer and higher DNA binding affinities than
copolymers with longer PMPC blocks. When the percentage of PMPC was 65%
and higher, the copolymers exhibited decreased affinity for DNA, suggesting that
the presence of a long PMPC block was deleterious to DNA complexation; moreover, above a 1:1 ratio, the presence of this steric stabilizer reduced the association
of the excess polymer with the polyplexes formed, as already observed for
PDMAEMA-b-PEG [182], and prevented aggregation, which was not the case for
copolymers with shorter PMPC blocks (10 or 20). PDMAEMA 40 -b-PMPC 30 and
PDMAEMA 40 -b-PMPC 40 formed well-defined polyplexes with hydrodynamic
diameters of approximately 150 nm, while PDMAEMA 40 -b-PMPC 50 formed larger
polyplexes with DNA with higher polydispersity. In the PMPC 30 -based copolymers
series, increasing the size of the PDMAEMA block resulted in higher condensation
ability as well as in smaller polyplexes in the sub-200 nm size range (except for
PDMAEMA 10 -b-PMPC 30 ), but also decreased the solubility of the polyplexes. As
expected, the presence of PMPC block reduced the cellular association of these
polyplexes, which correlated with their low transfection efficiencies (in the range of
free DNA). A content ratio of the MPC unit to tertiary amine higher than 2 was
required to produce spherical, well-condensed particles; MPC unit to amine ratios
lower than 2 produced irregular structures ranging from toroids to rods [230].
Narain and coworkers studied copolymers of N-(2-aminoethyl) methacrylamide
and 2-methacryloxyethyl phosphorylcholine as block or statistical copolymers
[PAEMA-b-PMPC, P(AEMA-stat-MPC)] and (3-aminopropyl) methacrylamide
and 2-methacryloxyethyl phosphorylcholine as block or statistical copolymers
[PAPMA-b-PMPC, P(APMA-stat-MPC)] (see Fig. 23d) [231] in the same range
of molecular weights as in the previous study [229] and around 50% modification in
MPC. Unfortunately, little information is given about the physico-chemical
characteristics of the polyplexes. Moreover, it was not clear which polymer:DNA
ratios were used in order to obtain polyplexes with diameters ranging from
50 to 200 nm, but in general statistical polymers yielded polyplexes with larger
diameters and irregular shapes compared to the corresponding diblock copolymers
(which yielded spherical nanoparticles). Hence, not only the composition of
MPC-based copolymers had an influence on the size and shape of the polyplexes
but, as already seen for other systems, the architecture also played an important
role. Copolymers with low molecular weights (6–7 kDa) showed lower gene
expression as compared to polymers with higher molecular weights (10–12 kDa).
A further increase in molecular weight led to a decrease in gene expression,
probably due to their higher cytotoxicity. Moreover, the block copolymer architecture resulted in better transfection efficiency than the statistical copolymer,
which was not due to an enhanced cellular uptake.
178
A. Bertin
comparable to PDMAEMA homopolymer and higher DNA binding affinities than
copolymers with longer PMPC blocks. When the percentage of PMPC was 65%
and higher, the copolymers exhibited decreased affinity for DNA, suggesting that
the presence of a long PMPC block was deleterious to DNA complexation; moreover, above a 1:1 ratio, the presence of this steric stabilizer reduced the association
of the excess polymer with the polyplexes formed, as already observed for
PDMAEMA-b-PEG [182], and prevented aggregation, which was not the case for
copolymers with shorter PMPC blocks (10 or 20). PDMAEMA 40 -b-PMPC 30 and
PDMAEMA 40 -b-PMPC 40 formed well-defined polyplexes with hydrodynamic
diameters of approximately 150 nm, while PDMAEMA 40 -b-PMPC 50 formed larger
polyplexes with DNA with higher polydispersity. In the PMPC 30 -based copolymers
series, increasing the size of the PDMAEMA block resulted in higher condensation
ability as well as in smaller polyplexes in the sub-200 nm size range (except for
PDMAEMA 10 -b-PMPC 30 ), but also decreased the solubility of the polyplexes. As
expected, the presence of PMPC block reduced the cellular association of these
polyplexes, which correlated with their low transfection efficiencies (in the range of
free DNA). A content ratio of the MPC unit to tertiary amine higher than 2 was
required to produce spherical, well-condensed particles; MPC unit to amine ratios
lower than 2 produced irregular structures ranging from toroids to rods [230].
Narain and coworkers studied copolymers of N-(2-aminoethyl) methacrylamide
and 2-methacryloxyethyl phosphorylcholine as block or statistical copolymers
[PAEMA-b-PMPC, P(AEMA-stat-MPC)] and (3-aminopropyl) methacrylamide
and 2-methacryloxyethyl phosphorylcholine as block or statistical copolymers
[PAPMA-b-PMPC, P(APMA-stat-MPC)] (see Fig. 23d) [231] in the same range
of molecular weights as in the previous study [229] and around 50% modification in
MPC. Unfortunately, little information is given about the physico-chemical
characteristics of the polyplexes. Moreover, it was not clear which polymer:DNA
ratios were used in order to obtain polyplexes with diameters ranging from
50 to 200 nm, but in general statistical polymers yielded polyplexes with larger
diameters and irregular shapes compared to the corresponding diblock copolymers
(which yielded spherical nanoparticles). Hence, not only the composition of
MPC-based copolymers had an influence on the size and shape of the polyplexes
but, as already seen for other systems, the architecture also played an important
role. Copolymers with low molecular weights (6–7 kDa) showed lower gene
expression as compared to polymers with higher molecular weights (10–12 kDa).
A further increase in molecular weight led to a decrease in gene expression,
probably due to their higher cytotoxicity. Moreover, the block copolymer architecture resulted in better transfection efficiency than the statistical copolymer,
which was not due to an enhanced cellular uptake.
178
A. Bertin