Bioactivities of Chitosan and Its Derivatives - Chitosan Based Hydrogels: Functions and Applications - page 157

53% and 59% against S-180 and H22, respectively, by At the same dose of 0.5 mg/kg by, chi-
tosan nanoparticles showed much higher efficacy than the chitosan group. TWI against S-180
and H22 reached 43% and 52%, respectively, while that of the chitosan group was just about
30%. cDDP as a positive control drug exhibited higher antitumor efficacy than chitosan nano-
particles. However, cisplatin also showed great side effects compared with chitosan and
nanoparticles. Chitosan nanoparticles resulted in only a small decrease in body weight of the
mice relative to the saline control, which indicated weak side effects. On the contrary, cDDP
led to a significant loss in body weight of mice. In the saline control group, 6 out of 12 and 7
out of 12 mice, separately in S-180 and H22 mouse models, died due to the transfer of tumor
on the seventh day; cDDP also had a lethal toxicity of 4 out of 12 and 3 out of 12 mice, respec-
tively, while in chitosan and nanoparticles groups, no lethal toxicity occurred for the inhibi-
tion of tumor growth. The histopathological slices from the liver and kidney tissues were
also examined by a microscope. No pathological changes due to the administration of nano-
particles were seen, which also indicated weak side effects of chitosan nanoparticles.
For the S-180-bearing mouse model, at the same dose, the efficacy of chitosan nanopar-
ticles (40 nm) by oral administration (p.o.), i.p. injection, and i.v. injection was 43%, 40%,
and 49%, respectively. For the H22-bearing mouse model, the TWI of chitosan nanoparti-
cles by the three administration routes was 52%, 51%, and 54%, respectively. The results
showed that chitosan nanoparticles exhibit effective antitumor activities using different
administration routes.
3.4.4.3 Chitosan Colloidal Drug Carrier Systems for Antitumor Activity
The oral route for colloidal drug carrier systems remains the most convenient and popu-
lar way of administration [197]. However, many anticancer drugs by oral administration
are not bioavailable and adsorbable/interactive in the GI tract, because the drugs could be
eliminated from the first-pass extraction by the cytochrome P450-dependent metabolic
processes and the overexpression of the plasma membrane transporter P-glycoprotein
(P-gp) in the physiological systems involved (intestine, liver, etc.) [198]. Application of
nanoparticles with size small enough to improve adhesion and absorption to the intesti-
nal cells and to escape from the recognition of P-gp may provide better solutions for oral
administration (p.o.) of anticancer drugs. It is currently accepted that nanoparticles are
taken up by the M-cells of PPs and the isolated follicles of GALT and also via the entero-
cytes [199]. Recently, positively charged colloidal particles were shown to be able to
increase the electrostatic interaction between particles and negatively charged mucin on
the mucosal surface, thus improving their bioavailability and reducing their side effects.
Chitosan nanoparticles exhibited positive charge and small particle size, which is respon-
sible for their in vivo e f ic ac y.
Conventional colloidal carriers are rapidly removed from the bloodstream by the reticu-
loendothelial system (RES), which is a part of the mononuclear phagocyte system (MPS)
after i.v. administration [200]. Nanoparticulate systems have been used to improve the
blood circulating time and tumor-targeting efficacy of vincristine [201], because the tumor
vascular permeability allows the penetration of particles up to 400 nm in diameter [202].
Therefore, the antitumor efficacy of chitosan nanoparticles administered by i.v. injection is
probably attributed to their small particle size.
Particle size has been proved to be an important feature related to obtaining optimal in vitro
efficacy of chitosan nanoparticles. Particle size also has a crucial impact on the in vivo fate of
a particulate drug delivery system [203]. Decreasing particles size can increase the surface-to-
volume ratio and specific surface area, which could increase the dissolution and thus increase