Environment–Stimuli Response of Chitosan-Based Hydrogels - Chitosan Based Hydrogels: Functions and Applications - page 247

different acids increase as follows: nitric acid < chloroacetic < hydrochloric < carboxylic
acids (formic, acetic propionic, butyric, isobutyric) < lactic acid. Hydrogels prepared with
carboxylic acids showed higher viscosity than inorganic acids.
However, Ma and coworkers [53] found that the chitosan/GP system does not behave
appropriately as a pH-sensitive drug carrier. Its swelling degree decreases in both acidic
and basic media. It showed high initial drug release in both acidic and basic conditions. At
acidic medium, the amino groups in chitosan/GP hydrogel are protonated and interact
with the free GP, which results in shrinkage of hydrogel. At basic medium, the ionic inter-
action between chitosan and GP is destroyed, which results in weight loss of the hydrogel
in solution and the swelling degree decreases. Quaternized chitosan/GP hydrogels have
appropriate pH sensitivity, and dissolve promptly in acidic solution, whereas they nearly
kept their original state in neutral or basic conditions. However, compared to the chitosan/
GP system, the thermosensitivity of quaternized chitosan/GP hydrogels decreases because
quaternization decreased the crystallinity and improved the water solubility of chitosan,
both of which contributed to reducing the gelation capacity. On the other hand, polymer
interchain repulsion due to the high cationic charge can also hinder polymer gelation.
Therefore, high SD is not beneficial for the gelation formation of the quaternized chitosan/
GP system [54]. In order to overcome this disadvantage, PEG is incorporated into the quat-
ernized chitosan/GP system. The chitosan/PEG/GP system has excellent temperature and
pH sensitivity, which can be utilized for facilitating the nasal drug delivery of peptide
drug [55].
5.3.2 Chitosan/Amphiphilic Polymer Thermosensitive Hydrogels
5.3.2.1 Chitosan/Pluronic Hydrogels
Triblock poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), (PEO-PPO-
PEO) copolymer (commercially available as Pluronic or Poloxamers) is well known to have
a fast thermally reversible property. Some of them have been proved by FDA. The LCST
could be controlled by the ratio of the hydrophobic PPO segment to the hydrophilic PEO
segment. The more the PPO constituents, the lower the LCST. Most of the Pluronic have an
LCST well above normal body temperature. Pluronic F127 is found to gel at a concentration
of 20 wt% at 25°C, which is less than that of the other members of the Pluronic series. At
room temperature (<25°C), the solution behaves as a mobile liquid, which is transformed
into a transparent gel at body temperature [56]. Chitosan-g-Pluronic 127 (CP) also exhibits
reversible thermosensitive properties at 30-35°C according to the incorporated Pluronic
concentration without any treatment. The LCST of CP is lower than that of Pluronic itself
at the same concentration. Sol-gel transition of CP does not occur if chitosan is over 17 wt%
in the copolymer owing to the increased hydrophilic property of chitosan [57]. At low
temperature, the CP copolymer is retained in the monomer state (solution phase). With
increasing temperature, CP aggregates are formed by hydrophobic interaction and CP
hydrogels are formed by packing of the aggregates in the aqueous solution ( cf. Figure 5.18 ) .
The hydrophobic interactions of the PPO group and dehydrated chitosan were suggested
to be the main force driving the formation of CP hydrogels [58].
5.3.2.2 Chitosan/PNIPAAm Hydrogels
Poly( N -isopropylacrylamide) (PNIPAAm) is a well-known member of the thermorespon-
sive polymer family. Its transition from a hydrophilic to a hydrophobic structure occurs