Chitosan-Based Gels for the Drug Delivery System - Chitosan Based Hydrogels: Functions and Applications - page 275

immunological response. Therefore, the main advantages of IPN are that relatively dense
hydrogel matrices can be produced, which feature stiffer and tougher mechanical proper-
ties, more widely controllable physical properties, and (frequently) more efficient drug
loading compared to conventional hydrogels.
Although cross-linking density, hydrogel porosity, and gel stiffness can be adjusted in
IPN-based hydrogels according to the target application, they have difficulty encapsulat-
ing a wide variety of therapeutic agents, especially sensitive biomolecules. In addition,
IPN preparation requires the use of toxic agents to initiate or catalyze the polymerization
or to catalyze the cross-linking. Complete removal of these materials from the hydrogel is
challenging, making the clinical application problematic [4].
6.4 Geometries of Chitosan Gels and Their Preparation Methods
Chitosan-based gels for DDSs have been fabricated into a variety of different shapes and
geometries for various administration routes such as oral, buccal, nasal, transdermal, par-
enteral, vaginal, cervical, intrauterine, and rectal. Different methods were used in order to
obtain these shapes and geometries.
6.4.1 Scaffolds
Hydrogel can be made into bulk matrices with different shapes, that is, scaffolds, for sev-
eral bioapplications, especially for tissue engineering, such as hard tissue replacement.
Certain active agents or bioactive molecules (i.e., growth factors and antibiotics) can be
released from these scaffolds to enhance the replacement. Scaffolds are prepared into vari-
ous shapes in terms of the defects that are needed to be replaced. Chitosan is a good can-
didate for preparing these types of matrices [16].
Freeze-drying or lyophilization is the most popular technique to fabricate chitosan-
based scaffolds [79]. Solutions of chitosan are frozen to result in phase separation. After
drying in a lyophilizer, ice is removed, generating a porous material whose pore size and
orientation can be controlled by variation of the freezing rate. Porous chitosan scaffolds
can also be prepared using a rapid prototyping system. Chitosan matrix was endowed
with special shapes and microstructure through computational modeling. Neutralization
of the acetic acid by the sodium hydroxide results in a precipitate to form a gel-like chito-
san structure [80].
Recently, a new supercritical CO 2 fluid-assisted process for the production of chitosan
scaffolds was proposed [81]. This method consists of three steps: formation of a chitosan
hydrogel by thermally induced phase separation; substitution of water with a suitable sol-
vent; and drying of the gel using supercritical CO 2 . Using this process, chitosan nanostruc-
tured networks were produced with filaments of diameters around 50 nm, without any
collapse of the gel nanostructure, characterized by high porosity (>91%) and high compres-
sive modulus (150 kPa).
6.4.2 Particles and Spheres
Hydrogels can be confined to smaller dimensions such as microparticles or microspheres.
When the size of microparticles is in the submicrometer range, they are known as