Biomedical Engineering Reference
In-Depth Information
Fig. 3
Poly
(2-(dimethylamino)ethyl
methacrylate) (PDMAEMA)
n
O
O
N
(especially systemic administration) using PDMAEMA has been largely limited,
since polyplexes based on this polymer could induce severe aggregation of erythro-
cytes (Verbaan et al.
2001
). Attempts have been made to improve the transfection
efficiency of PDMAEMA by chemical modifications. These studies concerned the
incorporation of additional tertiary amino groups in each structural unit to promote
the 'proton sponge' effect (Funhoff et al.
2004a
), the change of ammonium groups
in PDMEMA to pyridine, imidazole, and carboxylic acid functionalities to improve
endosomal escape (Dubruel et al.
2003
), the incorporation of guanidinium side
groups to facilitate membrane penetration (Funhoff et al.
2004b
). In addition,
PDMEMA has been copolymerized with variety of monomers such as methyl meth-
acrylate, N-vinyl-pyrrolidone, and ethoxytriethylene glycol methacrylate in order to
reduce its cytotoxicity (van de Wetering et al.
1998, 2000
). Thorough these proce-
dures, DMAEMA based polycations with a better transfection/toxicity ratio could
be reached.
3.5
Biodegradable Polycations
For the clinical applications of polymeric carriers for gene therapy, their long-term
fate in the host has to be considered. Biocompatible and biodegradable polymers
that can be degraded
in vivo
are therefore advantageous. In addition to biodegradable
PEI and PLL, other degradable polymers have been synthesized and investigated
for gene delivery (Fig.
4
). These polymers include poly[a-(4-aminobutyl)-L-
glycolic acid], poly(4-hydroxy-L-proline ester), poly(amino esters), polyphosphoe-
sters and polyphosphoramidates, and polyphosphazenes. Depending on their
structures, these polycations can be hydrolyzed within different time periods.
3.5.1
Poly[a-(4-Aminobutyl)-L-Glycolic Acid]
Poly[a-(4-aminobutyl)-L-glycolic acid] (PAGA) is a biodegradable analogue of
PLL, which was synthesized by the polymerization of N
e
-cbz-L-oxylysine mono-
mers followed by a deprotection (Fig.
4a
) (Lim et al.
2000b
). PAGA could effectively
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