Environment–Stimuli Response of Chitosan-Based Hydrogels - Chitosan Based Hydrogels: Functions and Applications - page 245

5.3.1.4 Chitosan/Polyol Salt Thermosensitivity Hydrogels
Chitosan/glycerophosphate (chitosan/GP) hydrogel, a novel thermosensitive hydrogel
first reported by Chenite et al. [42], is an important system due to its sol-gel transition at
body temperature. Chitosan/GP is a physical hydrogel formed when hydrogen bonds
between chitosan/GP and water become unstable at higher temperatures. As shown in
Figure 5.16, this system remains liquid at room temperature and solidifies into a hydrogel
as the temperature is increased to body temperature [43]. Chitosan/GP hydrogels have a
heterogeneous microstructure, with large interconnected solvent-rich areas and a
polymer-rich phase of agglomerates that aggregate into chains and large volume particu-
lates ( cf. Figure 5.17). GP plays two essential roles in the chitosan/CG system: (1) to increase
the pH value of chitosan solution to the physiological range of 7.0-7.4 and to prevent imme-
diate precipitation or gelation of chitosan solution, which is due to its mild basic character
and potentially due to the attraction of phosphate moieties of GP to the remaining charged
amine of chitosan, and thereby exposing the glycerol moiety to separate chitosan chains in
solution and maintain its solubility at low temperature; (2) to allow for controlled hydrogel
formation when an increase in temperature is imposed [44]. There are three interactions in
the chitosan/GP system [45]: (1) electrostatic attraction between the amino group of chito-
san and the phosphate group of glycerophosphate; (2) hydrogen bonding between chito-
san chains; and (3) chitosan-chitosan hydrophobic interactions. At low temperatures, GP
can promote the protective hydration of the chitosan chains; strong chitosan-water inter-
actions protect the chitosan chains against aggregation. Chitosan adopts a compact con-
formation due to intramolecular hydrogen bonds, and the physical junctions that could
form a gel are confined inside the coil. It is therefore a poor conformation to build up a
three-dimensional (3D) structure because of the difficulty of creating contacts between the
junction zones [46]. Upon heating, sheaths of water molecules are removed by the glycerol
moiety, and new hydrogen bonds form between hydrophobic groups as they collapse to
form separate domains. The hydrophobic associations cooperate to form junction points
and chitosan molecules can unfold freely, which in turn allows the association of chitosan
macromolecules. Moreover, GP is freely diffusible after gelation and is not retained in the
hydrogels [47].
In general, the thermosensitivity of chitosan/GP solution can be controlled by the DD of
chitosan, the MW of chitosan, the concentration of chitosan, the amount of GP, and the
medium. (1) The hydrogel of chitosan/GP can rapidly form at body temperature when the
DD is ca. 75.4%, whereas chitosan/GP hydrogels with other DD values form either slowly
or remain unchanged. Thus, the optimal DD for chitosan/GP thermosensitive hydrogel
preparation is 75.4% [48]; (2) the increase of MW is favorable for hydrogel transition and a
Figure 5.16
Chitosan/GP formulation at room temperature (left) and at 37°C (right).