Chitosan-Based Gels for the Drug Delivery System - Chitosan Based Hydrogels: Functions and Applications - page 289

to release its contents slower at 37°C than at 25°C. The temperature-sensitive phenomenon
was attributed to the hydrophobic interaction of PEDA chain overwhelming the H-bonding
of polymer chain with water when the temperature increased. Thus, the drug release
behavior could be controlled further in this way.
PEC hydrogels can also be used as dual-sensitive carriers for ionic drugs. PEC films
composed of chitosan and an anionic polymer, PAOMA copolymer, were created [132]. The
drug release characteristics of this PEC in response to changes in environmental pH and
temperature were studied using salicylic acid as the model drug. Both a decrease in pH
from 7.2 to 3.8 and a decrease in temperature from 50°C to 25°C resulted in a correspond-
ing decrease in the drug release rate. According to the authors, this responsiveness was
because of the repulsive forces between the carboxyl groups in PAOMA and the anionic
groups in model drugs at higher pH and the increase of release area caused by the phase
transition of PAOMA at higher temperature.
Recently, a new method was employed to prepare smart microgels that consist of well-
defined temperature-sensitive cores with pH-sensitive shells [133]. The microgels were
synthesized by the aqueous graft copolymerization of NIPAM from chitosan. As a result,
the cores were composed of well-defined poly( N -isopropylacrylamide) whereas the shells
were composed of chitosan. Therefore, their responsiveness to pH and temperature can be
manipulated individually. This unique smart hydrogel may be applicable in a further DDS
for a certain purpose.
6.6.2.3 Electric-Sensitive Release
Electric-sensitive delivery systems are usually prepared from polymers containing elec-
trosensitive moieties such as polyelectrolytes. Under the influence of an electric field, elec-
troresponsive hydrogels generally deswell or bend, depending on the shape and orientation
of the gel. The gel bends when it is parallel to the electrodes, whereas deswelling occurs
when the hydrogel lies perpendicular to the electrodes [134]. The main mechanisms of
drug release from the electroresponsive hydrogels include ejection of the drug solution
during deswelling, diffusion, electrophoresis of charged drugs, and electro-induced gel
erosion [135]. The use of chitosan gels as matrices for electrically modulated drug delivery
was investigated recently [136]. In this study, release time profiles for neutral (hydrocorti-
sone), anionic (benzoic acid), and cationic (lidocaine hydrochloride) drug molecules
from chitosan gels were monitored in response to milliampere currents as a function of
time. The results showed that drug release from the various formulations, involving several
electrokinetic and physicochemical factors, was greater at higher milliampere current.
The author stated that hydrocortisone release from the gels was probably due to the
electroosmotic and diffusional forces, while the release of benzoic acid and lidocaine
hydrochloride involved the additional contribution of drug polarity.
IPN hydrogels made up of PEG macromer and chitosan that exhibited electrosensitive
behavior have been synthesized [137]. The electrical response of IPN hydrogels was inves-
tigated by applying electrical current to the hydrogels immersed in a NaCl solution. The
extent of the bending behavior of the IPN hydrogel depends on IPN hydrogel composition
and applied electric field strength. The applied voltage can increase the deformation of the
hydrogels in both extent and speed. The author also proposed that the bending behavior
of these swollen hydrogels under an electric field at various applied voltages could be
applicable for electrically controlled drug release systems.
More recently, a nanocomposite hydrogel composed of chitosan and montmorillonite
(MMT) has been prepared and the release of VB 2 under electrostimulation was studied