Application of Chitosan-Based Gels in Pharmaceuticals - Chitosan Based Hydrogels: Functions and Applications - page 311

7.1 Introduction
The history of the studies of polysaccharide chitosan dates back to the nineteenth century.
However, it is only in the last couple of decades that people have considered chitosan as
a kind of biomedical and drug delivery material. Chitosan is a deacetylated form of chi-
tin, which is the second most abundant polymer in nature after cellulose. The slight dif-
ference between the chemical structures of chitin and chitosan has, however, resulted in
very different consequences in terms of their applications to drug delivery. Chitin is not
soluble in water and in most of the common organic solvents used in pharmaceutical
industry. Therefore, it is not useful for the development of drug delivery devices. In con-
trast with chitin, chitosan base can be protonized in acidic solutions and becomes solu-
ble. The positive charges on the chitosan molecule (CM) enable it to interact with
polyanions, a process that has been used to obtain micro- and nanoparticulate or nano-
gel drug delivery systems. In addition to its polycationic characteristics, chitosan has
shown some other excellent properties (e.g., nontoxicity, biocompatibility, mucus adhe-
sion, and biodegradation). As a result, chitosan has been used for a variety of drug deliv-
ery systems [1,2]. Some of the chitosan-based drug delivery systems are summarized in
Table 7.1.
The modalities of chitosan-based drug delivery systems include tablets, capsules, micro-
spheres/microparticles, nanoparticles, beads, films, and gels. All these modalities can be
regarded as ramifications of gels. The review given below addresses the recent trends in
the area of chitosan-based drug delivery systems.
7.2 Methods of Preparation of Drug Delivery Systems Based on Chitosan
Different methods have been developed to prepare chitosan drug delivery systems. The
choice of the methods depends on factors such as particle size requirement, thermal and
chemical stability of the active agent, reproducibility of the release kinetic profiles, stabil-
ity of the final product, and residual toxicity associated with the final product. In this
review we attempt to outline the different methods used in the preparation of chitosan
drug delivery systems.
7.2.1 Methods of Preparation of Micro/Nanogels based on Chitosan [1]
7.2.1.1 Emulsion Cross-Linking
This method utilizes the reactive functional amine group of chitosan to cross-link with
aldehyde groups of the cross-linking agent. In this method, water-in-oil emulsion is pre-
pared by emulsifying the chitosan aqueous solution in the oil phase. Aqueous droplets
are stabilized using a suitable surfactant. The stable emulsion is cross-linked by using
an appropriate cross-linking agent such as glutaraldehyde to harden the droplets.
Microspheres are filtered and washed repeatedly with n -hexane followed by alcohol and
then dried [3]. With this method, sizes of the particles can be controlled by regulating
the sizes of aqueous droplets. However, the particle size of the final product depends on
the amount of cross-linking agent used when hardening in addition to the speed of