Bioactivities of Chitosan and Its Derivatives - Chitosan Based Hydrogels: Functions and Applications - page 156

The sample LCOS containing more molecules with lower COSs showed lower activity.
This may have been due to the high content of pentamers or smallers, which are known to
have no activity [187]. The sample UCOSAc from acetylation of UCOS-B also showed high
antitumor activity, but it has a different optimum dose from UCOS-B. Nevertheless, a part
of UCOSAc had poor water solubility.
It is interesting that the oral administration of water-soluble chitosan was effective in
decreasing the weight of tumor, because lentinan was reported to have no antitumor effects
by p.o. [188]. Water-soluble chitosan with small size also had a lower antitumor effect. The
experiment shows that there were no significant differences in the spleen weights. Ftorafur
as the positive group had a high antitumor effect and a strong side effect.
Many polysaccharides are shown to exhibit growth-inhibitory effects against solid-type
tumors in experimental animals. The antitumor activity of polysaccharide seems to depend
not only on chemical structure but also on molecule size [189]. For example, schizophyllan
exhibits most activity within the range of 100-200 kDa, and no activity below 10 kDa. COSs
and their N -acetylated analogs, which are soluble in basic physiological environment,
might be good candidates for biological activity. Hexa- N -acetylchitohexaose and chito-
hexaose were reported to be growth inhibitory against S-180 and MM-46 solid tumors
transplanted into mice when given by i.v. administration [190]. The hexaoses were also
growth inhibitory to Meth-A solid tumor transplanted in mice, but the lower homologs of
the hexaoses were unable to exhibit the same effect [191]. Although the mechanisms of the
antitumor activity of hexa- N -acetylchitohexaose and chitohexaose were different, they can
be assumed to be acceleration of the production of and response to IL-1 and IL-2 for matu-
ration of splenic T-lymphocytes to killer T-cells [187]. Seo et al. [192] demonstrated that
water-soluble chitosan oligomers could activate murine peritoneal macrophases for tumor
cell killing in the presence of IFN-γ. The amino groups as base groups might contribute a
lot to the antitumor effect of chitosan.
3.4.4.2 Antitumor Activity of Chitosan Nanoparticles
The unique character of nanoparticles for their small size and quantum size effect could
make chitosan nanoparticles exhibit biological activities [193]. Chitosan nanoparticles
with small particle size and enhanced zeta potential have been prepared and character-
ized in previous reports [193-194], and their in vitro cytotoxic effects against various
human tumor cell lines have also been studied. It was shown that chitosan nanoparticles
with small particle size and positive surface charge could exhibit higher antitumor activ-
ity than other chitosan derivatives, and the physiochemical properties of nanoparticles
such as particle size and zeta potential could have a significant effect on their efficacy [195].
The antitumor mechanism of chitosan nanoparticles was related to its membrane-dis-
rupting and apoptosis-inducing activities [196].
To evaluate the in vivo antitumor activity of chitosan nanoparticles with different particle
sizes, against the mouse tumor model, S-180 tumor and mouse hepatoma H22 (H22) with
chitosan and cisplatin (cDDP) were used as reference drugs, and 0.9% saline solution was
used as the blank control. Drugs were administered from the fifth day after establishing the
mouse model, when the volume of subcutaneous tumor in mice grew by about 3 mm 3 .
Chitosan nanoparticles with different doses and different particle sizes were administered
once daily by i.v. injection, i.p. injection, and p.o., respectively, for seven consecutive days. The
results showed that chitosan nanoparticles exhibited very impressive antitumor efficacy in
vivo against S-180 and H22, higher than the chitosan group. Chitosan nanoparticles elicited
dose-dependent tumor-weight inhibitions (TWIs); the efficacy at a dose of 2.5 mg/kg achieved