The Complex World of Polysaccharides
14
Chitosan details
(DD, MW)
Modification
Assessment
IC50
95% DD, 18.7 kDa Steric acid conjugation
micelle
In vitro ,A549 cells
369±27 μg/ml
95% DD, 18.7 kDa teric acid conjugation and
entrapment in micelle
In vitro ,A549 cells
234±9 μg/ml
97% DD, 65 kDa N-octyl-O-sulphate
Invitro, primary rat
hepatocytes
>200 mg/ml
87% DD, 20, 45,
200, 460 kDa
None, aspartic acid salt In vitro, Caco-2 cells,
pH 6.2
0.67±0.24, 0.61±0.10,
0.65±0.20, 0.72±0.16
mg/ml
87% DD, 20, 45,
200, 460 kDa
None, glutamic acid salt
0.56±0.10, 0.48±0.07,
0.35±0.06, 0.46±0.06
mg/ml
87% DD, 20, 45,
200, 460 kDa
None, Lactic acid salt
0.38±0.13, 0.31±0.06,
0.34±0.04, 0.37±0.08
mg/ml
87% DD, 20, 45,
200, 460 kDa
None, hydrochloride salt
0.23±0.13, 0.22±0.06,
0.27±0.08, 0.23±0.08
mg/ml
78% DD, <50 kDa None, lactic acid salt
In vitro B16F10 cells 2.50 mg/ml
82% DD, 150–170
kDa
None, lactic acid salt
In vitro B16F10 cells 2.00±0.18 mg/ml
>80% DD, 60–90
kDa
None, glutamic acid salt In vitro B16F10 cells 2.47±0.14 mg/ml
77% DD, 180–230
kDa
None, lactic acid salt
In vitro B16F10 cells 1.73±1.39 mg/ml
85% DD, 60–90
kDa
None, hydrochloric acid
salt
In vitro B16F10 cells 2.24±0.16 mg/ml
81% DD, 100–130
kDa
None, hydrochloric acid
salt
In vitro B16F10 cells 0.21±0.04 mg/ml
100% DD, 152 kDa Glycol chitosan
In vitro B16F10 cells 2.47±0.15 mg/ml
100% DD, 3–6 kDa 20, 44, 55% Trimethyl
chitosan, chloride salt
In vitro, MCF7 and
COS7 cells, 6 h & 24 h
>10 mg/ml
100% DD, 3–6 kDa 94% Trimethyl chitosan,
chloride salt
In vitro, MCF7, 6 h
1.402±0.210 mg/ml
100% DD, 3–6 kDa 94% Trimethyl chitosan,
chloride salt
In vitro, COS7, 6 h
2.207±0.381 mg/ml
100% DD, 100 kDa 36% Trimethyl chitosan,
chloride sal
In vitro, MCF7, 6 h
0.823±0.324 mg/ml
100% DD, 100 kDa 36% Trimethyl chitosan,
chloride sal
In vitro, COS7, 6 h
>10 mg/ml
Is Chitosan a New Panacea? Areas of Application
15
Chitosan details
(DD, MW)
Modification
Assessment
IC50
84.7% DD, 400,
100, 50, 25, 5 kDa
40% Trimethyl chitosan In vitro, L929 cells, 3 h 30, 70, 90, 270, >1000
μg/ml
84.7% DD, 1.89
MDa
12% PEG modified 40%
trimethyl chitosan
In vitro, L929 cells, 3 h 220 μg/ml
84.7% DD, 3.6
MDa
25.7% PEG modified 40%
trimethyl chitosan
In vitro, L929 cells, 3 h 370 μg/ml
84.7% DD, 300
kDa
6.44% PEG modified 40%
trimethyl chitosan (and
all PEG modified TMC
with lower Mw)
In vitro, L929 cells, 3 h >500 μg/ml
97% DD, 65 kDa N-octyl-O-sulphate
In vivo, IV, mice
102.59 mg/kg
97% DD, 65 kDa N-octyl-O-sulphate
n vivo, IP, mice
130.53 mg/kg
Table 1.
Toxicity of chitosan
and chitosan derivatives
Table taken from [94]
In a series of articles are described the effects of chitosans with differing molecular weights
and degree of deacetylation in vitro and in vivo. Toxicity was found to be degree of
deacetylation and molecular weight dependent. At high DD the toxicity is related to the
molecular weight and the concentration, at lower DD toxicity is less pronounced and less
related to the molecular weight [93].
A summary of toxicities of chitosan and derivatives assessed through IC
50
values is
presented in the next table [94].
From this table it can be gathered that most chitosans (and derivatives) are not significantly
toxic compared to a toxic polymer such as polyethylenimine [94].
It appears that the toxicity of chitosan is related to the charge density of the molecule,
toxicity increases with increasing density. It appears that there is a threshold level below
which there are too few contact points between a molecule and the cell components to
produce a significantly toxic effect. This balance is between 40 and 60% DD, or degree of
trimethylation, although any sufficiently small chitosan (<10 kDa) is not appreciably toxic.
Modifications that do not increase the charge on the molecule seem to have little effect on
the toxicity beyond that of the native molecule [94].
17. Antimicrobial activity
The exact mechanism by which chitosan exerts its antimicrobial activity is currently
unknown, it has been suggested that the polycationic nature of this biopolymer that forms
from acidic solutions below pH 6.5 is a crucial factor. Thus, it has been proposed that the
positively charged amino groups of the glucosamine units interact with negatively charged
components in microbial cell membranes, altering their barrier properties, and thereby