Biomedical Engineering Reference
In-Depth Information
O
OH
OH
NH
2
NH
HO
HO
O
O
O
HO
O
O
O
O
HO
NH
2
NH
2
OH
n
OH
Chitosan
OH
O
OH
O
O
OH
HO
HO
O
HO
OH
O
HO
OH
O
O
OH
HO
OH
O
O
RO
OR
O
HO
O
HO
OH
n
O
OR
O
OH
HO
OH
HO
O
O
12-20% of R: H
88-80% of R: -(CH
2
)
2
-N-CH
2
-CH
3
)
2
O
OH
HO
DADE-dextran
β
-Cyclodextrin
Figure 4.19
Chemical structures of biopolymers.
more effective in entrapping DNA than low-molecular-weight analogues. It was
shown that transfection efficiency increases with the molecular weight of chitosan
polyplexes (213 kDa 98 kDa 48 kDa 17 kDa) when evaluated
in vitro
against
A549 cell lines
[349]
.
Chitosan with molecular weight 15-70 kDa and degree of deacetylation 80-90%
had high transfection efficiency
[345]
. In another study, chitosan of 162 kDa and
83% degree of deacetylation had the highest transfection efficiency
[346]
. Degree of
deacetylation, rather than the molecular weight of chitosan, plays a critical role for
cellular uptake and cytotoxicity of DNA-chitosan polyplexes
[350]
. Increased charge
density of the deacetylated polymer imparts stability to polymers. However, chito-
san with moderate degrees of deacetylation exhibited highest transfection efficiency
in vivo
.
Higher transfection efficiency of chitosan polyplexes can be achieved between pH
6.5 and 7.5, most favorably between pH 6.8 and 7.0. However, at pH below 6.5, cel-
lular uptake of chitosan polyplexes was noteworthy, but transfection efficiency was
low, possibly due to hindered endosomal release, whereas at a pH above 7.5, DNA
was dissociated from the complex, thereby hindering its cellular uptake
[345,351]
.
Chitosan-mediated gene delivery exhibited high-level gene expression with low
cytotoxicity. Surprisingly, the transfection efficiency of chitosan polyplexes in the
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