the regeneration reactions, which give rise to various novel biofunctional macromolecular products having the original or new types of organization [24]. The
chemical modification of chitosan is a powerful tool for controlling the interaction
of the polymer with drugs and thus to enhance the load capability to tailor the
release profile of the particles [112]. Chemically modified chitosan improves its
bulk properties for the preparation of sustained release systems. There are different
ways to chemically modify chitosan. Among them, chemical modification via graft
copolymerization seems promising as it can provide a wide variety of molecular
characteristics. In view of increasing the water solubility of chitosan, amphiphilic
derivatives of chitosan have received much attention by researchers. To prepare
such types of compound, hydrophobic moieties are introduced to the chitosan
backbone using methodologies such as alkylation, acylation, and graft copolymerization. Many works related to chemical modification of chitosan have been reported
in the literature. This section will describe the procedures for some of the chemically modified chitosans.
8.1 Chitosan-g-PEG Copolymer [113]
Under normal conditions, neither the hydroxyl groups nor amino groups of chitosan
react with the hydroxyl end groups of poly(ethylene glycol) (PEG). Therefore,
the monomethyl ether of PEG (mPEG) is used. Firstly, mPEG is converted into
PEG-aldehyde (mPEG-CH═O) by oxidizing it with DMSO and acetic anhydrate
[114]. Then, mPEG-CH═O is reacted with chitosan in the presence of NaCNBH 3
in order to prepare the grafted materials. In this case, Schiff base is produced
first by the reaction of an amino group of chitosan with the aldehyde group of
mPEG-CH═O, followed by reductive amination to obtain the copolymer of
chitosan and PEG (CS-g-PEG). In brief, chitosan (0.5 g) was dissolved in a mixture
of aqueous 2% acetic acid (40 mL) and methanol (20 mL) and then a previously
prepared aqueous solution of mPEG-CH═O of molecular weight (M w ) 2,000 g/mol
(2.9 g) was added dropwise under stirring for 30 min at room temperature [115].
After that, the pH of the chitosan/PEG-aldehyde solution was gradually increased
by adding Na 2 CO 3 until pH 6. After 1 h, NaCNBH 3 (0.183 g) was added and the
mixture was stirred for 5 h at 55
C. The precipitate was obtained by pouring the
reaction mixture into a saturated ammonium sulfate solution [116]. The precipitate
was filtered and dialyzed against aqueous 0.05 M NaOH and water alternately for
96 h using a dialysis membrane bag with a molecular weight cut-off of 12,400.
The solutions were frequently changed until the pH of the external water phase
reached 7. The material from the inner solution was freeze-dried and washed
with ethanol and acetone in order to remove unreacted mPEG in the system.
Finally, after drying in a vacuum oven, a white powder of CS-g-PEG was obtained.
Basically, it is a two-step process. A schematic diagram for the synthesis of CS-g-PEG
copolymer is shown in Fig. 7.
Engineering of Polysaccharides via Nanotechnology
103
chemical modification of chitosan is a powerful tool for controlling the interaction
of the polymer with drugs and thus to enhance the load capability to tailor the
release profile of the particles [112]. Chemically modified chitosan improves its
bulk properties for the preparation of sustained release systems. There are different
ways to chemically modify chitosan. Among them, chemical modification via graft
copolymerization seems promising as it can provide a wide variety of molecular
characteristics. In view of increasing the water solubility of chitosan, amphiphilic
derivatives of chitosan have received much attention by researchers. To prepare
such types of compound, hydrophobic moieties are introduced to the chitosan
backbone using methodologies such as alkylation, acylation, and graft copolymerization. Many works related to chemical modification of chitosan have been reported
in the literature. This section will describe the procedures for some of the chemically modified chitosans.
8.1 Chitosan-g-PEG Copolymer [113]
Under normal conditions, neither the hydroxyl groups nor amino groups of chitosan
react with the hydroxyl end groups of poly(ethylene glycol) (PEG). Therefore,
the monomethyl ether of PEG (mPEG) is used. Firstly, mPEG is converted into
PEG-aldehyde (mPEG-CH═O) by oxidizing it with DMSO and acetic anhydrate
[114]. Then, mPEG-CH═O is reacted with chitosan in the presence of NaCNBH 3
in order to prepare the grafted materials. In this case, Schiff base is produced
first by the reaction of an amino group of chitosan with the aldehyde group of
mPEG-CH═O, followed by reductive amination to obtain the copolymer of
chitosan and PEG (CS-g-PEG). In brief, chitosan (0.5 g) was dissolved in a mixture
of aqueous 2% acetic acid (40 mL) and methanol (20 mL) and then a previously
prepared aqueous solution of mPEG-CH═O of molecular weight (M w ) 2,000 g/mol
(2.9 g) was added dropwise under stirring for 30 min at room temperature [115].
After that, the pH of the chitosan/PEG-aldehyde solution was gradually increased
by adding Na 2 CO 3 until pH 6. After 1 h, NaCNBH 3 (0.183 g) was added and the
mixture was stirred for 5 h at 55
C. The precipitate was obtained by pouring the
reaction mixture into a saturated ammonium sulfate solution [116]. The precipitate
was filtered and dialyzed against aqueous 0.05 M NaOH and water alternately for
96 h using a dialysis membrane bag with a molecular weight cut-off of 12,400.
The solutions were frequently changed until the pH of the external water phase
reached 7. The material from the inner solution was freeze-dried and washed
with ethanol and acetone in order to remove unreacted mPEG in the system.
Finally, after drying in a vacuum oven, a white powder of CS-g-PEG was obtained.
Basically, it is a two-step process. A schematic diagram for the synthesis of CS-g-PEG
copolymer is shown in Fig. 7.
Engineering of Polysaccharides via Nanotechnology
103