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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