Chitosan-Based Gels for the Drug Delivery System - Chitosan Based Hydrogels: Functions and Applications - page 265

that the hydrophobic block was introduced into chitosan, which could change the
strong hydrophilicity of chitosan and improve its properties as a DDS. The decomposition
of the ester linkages as well as the degradation of chitosan in the hydrogel caused the col-
lapse of the gel, which may last for 30 days [36]. The degradation behavior can be adjusted
by the ratio of ethylene oxide/propylene oxide, grafting percentage, and molecular weight
of Pluronic.

6.2.2.2 Chitosan-g-PEG

Bhattarai et al. [37,38] also developed a chitosan-poly(ethylene oxide) (PEO) copolymer
(chitosan-g-PEG) that was produced by chemically grafting monohydroxy PEG onto the
chitosan backbone using Schiff base and sodium cyanoborohydride chemistry ( cf .
Figure 6.5). The resultant copolymer was an injectable liquid at low temperature and trans-
formed to a semisolid hydrogel at body temperature. The hydrogel was proved to be capa-
ble of acting as a protein drug carrier by studying the release of bovine serum albumin
(BSA) as a model protein [38].

6.2.2.3 Chitosan-g-Cyclodextrin [20]

Cyclodextrin has gained prominence in recent years because its hydrophobic cavity is
capable of binding aromatic and other small organic molecules [20], and therefore facili-
tates the entrapment and controlled release of hydrophobic drugs [10]. Chitosan-g-
cyclodextrin is one of the most attractive drug vehicles for delivering hydrophobic
molecules. Tojima et al. [39] prepared chitosan-g-cyclodextrin via the reductive amination
strategy ( cf . Figure 6.6). Briefly, an aldehyde group was introduced into α-cyclodextrin.
The aldehyde group reacted with the amine group of chitosan when mixing their solu-
tions to form Schiff base, which was subsequently reduced using NaBH 3 CN as the reduc-
tive agent. A coupling reaction was also employed to prepare chitosan-g-cyclodextrin by
using EDC [40]. Details of the reaction procedure are shown in Figure 6.7 [20].

OH

O

O

HO

n

NH 2

Chitosan

(1) CH 3 O(CH 2 CH 2 CHO) m CH 2 CHO
(2) NaCNBH 3

OH

O

O

HO

n

NHCH 2 CH 2 (OCH 2 CH 2 ) m OCH 3

PEG-g-chitosan

Figure 6.5
Chemical reaction scheme for grafting PEG onto chitosan. (From Bhattarai, N., Matsen, F. A., and Zhang, M. Q.
2005. Macromol Biosci 5: 107-111. With permission.)