A study comparing PDMAEMA with PEGylated derivatives and different functional groups such as tertiary amine, pyridine, imidazole, and acid groups was
conducted by Schacht and colleagues [146]. They found that the presence of
methacrylic acid in P(DMAEMA-co-MA) (Fig. 7k) increased the amount of polymer needed for DNA condensation with increasing amount of acid groups, which
can be explained by the repulsive effect between anionic DNA and the negatively
charged carboxylate groups. A similar effect was observed for imidazolecontaining polymers, as the imidazole groups are not protonated under the experimental conditions. These results also correlated with the zeta potential
measurements: the greater the amount of these groups (negatively charged or
neutral), the lower the zeta potential of the polyplexes. P(DMAEMA-co-MA),
P(DMAEMA-co-HYMIMMA) (Fig. 7l), and P(DMAEMA-co-HENIMA)
(Fig. 7m) were able to condense DNA into nanoparticles with size <300 nm at a
charge ratio of 2:1 but with bimodal or trimodal distributions (not well-defined,
possibly due to aggregation).
PNIPAM Derivatives
Homopolymers of PNIPAM have a lower critical solution temperature
(LCST) around body temperature. The LCST of copolymers of PNIPAM such as
P(DMAEMA-co-NIPAM (Fig. 8a) gradually increased with increasing content of
DMAEMA (hydrophilic monomer) and was independent of the molecular weight
(38.3–45.7
C for a DMAEMA content of 15–30% and >80
C for a content of 80%)
[147]. All P(DMAEMA-co-NIPAM) copolymers (M w > 91 kDa), even with a low
DMAEMA content of 15 mol%, were able to bind to DNA. With increasing
NIPAM content, the charge density of the copolymer decreased and the P:DNA
ratio needed for condensation to occur increased. Concerning the polyplexes, with
increasing NIPAM content, the zeta potential of the polyplexes at the optimum
P:DNA ratio decreased, as did the cytotoxicity and transfection efficiency. The
authors postulated that these polyplexes interacted less with the negatively charged
membrane, thus leading to lower transfection efficiency. At 37
C, even if the LCST
was not passed, complexes made from low molecular weight polymers (independent of the content) or of high molecular weight with low DMAEMA content (15%)
showed poor properties as transfection agents, which was linked to their poor
stability.
The condensation properties of PLL-g-PNIPAM (Fig. 8b) were governed, like in
the last case, by the PNIPAM content related to the condensing units such as lysine
(higher content of PNIPAM, less condensation efficiency) but the molecular weight
of the PNIPAM grafts did not have a significant effect [148]. As also observed in
the previous study [147], the size of the complexes increased with increasing
PNIPAM content at 25
C due to an internal swelling of the hydrated PNIPAM
chains. At 38
C (above the phase transition of PNIPAM), the size of the polyplexes
decreased as a consequence of the collapse of PNIPAM chains, accompanied by a
higher structural density and thus a more difficult release of DNA.
144
A. Bertin
conducted by Schacht and colleagues [146]. They found that the presence of
methacrylic acid in P(DMAEMA-co-MA) (Fig. 7k) increased the amount of polymer needed for DNA condensation with increasing amount of acid groups, which
can be explained by the repulsive effect between anionic DNA and the negatively
charged carboxylate groups. A similar effect was observed for imidazolecontaining polymers, as the imidazole groups are not protonated under the experimental conditions. These results also correlated with the zeta potential
measurements: the greater the amount of these groups (negatively charged or
neutral), the lower the zeta potential of the polyplexes. P(DMAEMA-co-MA),
P(DMAEMA-co-HYMIMMA) (Fig. 7l), and P(DMAEMA-co-HENIMA)
(Fig. 7m) were able to condense DNA into nanoparticles with size <300 nm at a
charge ratio of 2:1 but with bimodal or trimodal distributions (not well-defined,
possibly due to aggregation).
PNIPAM Derivatives
Homopolymers of PNIPAM have a lower critical solution temperature
(LCST) around body temperature. The LCST of copolymers of PNIPAM such as
P(DMAEMA-co-NIPAM (Fig. 8a) gradually increased with increasing content of
DMAEMA (hydrophilic monomer) and was independent of the molecular weight
(38.3–45.7
C for a DMAEMA content of 15–30% and >80
C for a content of 80%)
[147]. All P(DMAEMA-co-NIPAM) copolymers (M w > 91 kDa), even with a low
DMAEMA content of 15 mol%, were able to bind to DNA. With increasing
NIPAM content, the charge density of the copolymer decreased and the P:DNA
ratio needed for condensation to occur increased. Concerning the polyplexes, with
increasing NIPAM content, the zeta potential of the polyplexes at the optimum
P:DNA ratio decreased, as did the cytotoxicity and transfection efficiency. The
authors postulated that these polyplexes interacted less with the negatively charged
membrane, thus leading to lower transfection efficiency. At 37
C, even if the LCST
was not passed, complexes made from low molecular weight polymers (independent of the content) or of high molecular weight with low DMAEMA content (15%)
showed poor properties as transfection agents, which was linked to their poor
stability.
The condensation properties of PLL-g-PNIPAM (Fig. 8b) were governed, like in
the last case, by the PNIPAM content related to the condensing units such as lysine
(higher content of PNIPAM, less condensation efficiency) but the molecular weight
of the PNIPAM grafts did not have a significant effect [148]. As also observed in
the previous study [147], the size of the complexes increased with increasing
PNIPAM content at 25
C due to an internal swelling of the hydrated PNIPAM
chains. At 38
C (above the phase transition of PNIPAM), the size of the polyplexes
decreased as a consequence of the collapse of PNIPAM chains, accompanied by a
higher structural density and thus a more difficult release of DNA.
144
A. Bertin