Bioactivities of Chitosan and Its Derivatives - Chitosan Based Hydrogels: Functions and Applications - page 160

TAble 3.5
Cytotoxicities of COS-SA, DOX HCl Solution, and DOX-COS-SA Against
MCF-7 Cells, and MCF-7/Adr Cells.

IC 50 n = 3( μ g mL − 1 ± SD)

Material MCF- 7 Cells MCF- 7/Adr Cells Reversal Power

COS-SA 223.7 ± 24.8 254.1 ± 18.0 —

DOX ⋅ HCl 0.11 ± 0.02 33.7 ± 13.7 —

DOX-COS-SA-3 1.27 ± 0.12 3.26 ± 0.36 10.5

DOX-COS-SA-6 2.22 ± 0.36 5.20 ± 0.38 6.5

DOX-COS-SA-10 4.54 ± 0.35 7.70 ± 0.90 4.4

Note: Reversal power was calculated from the equation of value of drug solution against
drug resistance cells; value of drug solution against drug sensitive cells; value of
DOX-COS-SA against drug resistance cells.

paclitaxel in the form of conjugates with LMWC [215]. DTX (i.v.) (10 mg/kg) showed a
marked weight loss, indicating severe toxicity. In contrast, neither high nor low doses of
the LMWC-DTX conjugate group exhibited body weight change when compared to the
saline control group, suggesting much lower toxicity. The LMWC-DTX conjugate (p.o.) is
comparably effective in inhibiting tumor growth but is much less toxic compared to the
same dose of DTX (i.v.). The much reduced toxicity may be due to the gradual or sustained
release of DTX from the LMWC-DTX conjugate into the bloodstream after oral adminis-
tration. The LMWC-based conjugate system may be used as a promising oral delivery
platform for sparingly soluble chemical drugs.

3.4.4.4 Self-Assembly Chitosan Derivatives for Antitumor Activity

Colloidal systems have found numerous applications as promising delivery vehicles for
drugs, proteins, antigens, and genes due to their low toxic side effects and enhanced thera-
peutic effects. Polymeric self-assembly systems (SAs) represent one type of colloidal sys-
tem that has been widely investigated in terms of micellar behavior in both biotechnology
and pharmaceutics. Precise control of size and structure is a critical design parameter of
micellar systems for drug delivery applications. To control the size of an SA, chitosan was
depolymerized with sodium nitrite, and hydrophobically modified with deoxycholic acid
to form the SA in aqueous media (Figure 3.26) [216]. The size of the SA could be varied from
130 to 300 nm in diameter.
Because of the chain rigidity of chitosan, the SA was suggested to have a cylindrical
bamboo-like structure, which could form only a very poor spherical form in a bird's nest-
like structure. In the test of the potential application of the SA as a gene delivery carrier, a
significant enhancement of transfection efficiency by the SA was observed against
COS-1 cells (up to a factor of 10). This approach to control the size and structure of the
chitosan-derived SA may find a wide range of applications in gene delivery as well as in
general drug delivery applications. Lee et al. reported the delivery of adriamycin (ADR)
using the SA of the deoxycholic acid-modified chitosan [217]. Deoxycholic acid was cova-
lently conjugated to chitosan via an hydrochloride[N-ethyl-N-(3-dimethylaminopropyl)]
carbodiimidehydrochloride (EDC)-mediated reaction to generate SA nanoparticles. ADR
was physically trapped inside the SA and slow release of ADR was thereby achieved.