Chitosan-Based Gels for the Drug Delivery System - Chitosan Based Hydrogels: Functions and Applications - page 260

its copolymers poly(l-glycolic acid) (PLGA), poly(ethylene glycol) (PEG) copolymers,
poly(cyanoacrylates), poly(anhydrides), poly(ortho esters), polyphosphazene, poly(vinyl
alcohol) (PVA), poly(vinyl pyrrolidone), poly(acrylic) acid (PAA), cellulose derivatives,
hyaluronic acid derivatives, alginate, collagen, gelatin, starch, dextran, and chitosan.
DDSs have capitalized on their wide-ranging hydrophobic and hydrophilic components
and their polymer-polymer, polymer-drug, polymer-solvent, or polymer-physiological
medium interactions [4]. Although many synthetic materials perform well for incorpo-
rating drugs and controlling sustained drug release, they may not be the most proper
candidates due to their nonbiodegradability, relative hydrophobicity, and poor biocom-
patibility. Natural polymers such as collagen, hyaluronic acid, and chitosan have a num-
ber of advantages over synthetic polymers. For example, the need for harsh processing
conditions is reduced, the material source is abundant, and production is both relatively
environmentally safe and of low cost [5]. All these combined with the properties of
good biocompatibility and biodegradability make natural macromolecules promising
drug vehicles.
As most natural polymers are hydrophilic, they are usually in the form of hydrogel
when used as drug carriers. Hydrogels are hydrated, water-insoluble polymeric net-
works cross-linked by water-soluble precursors [6-8]. They are able to swell and retain a
significant portion of water but are not dissolved when placed in an aqueous solution
[6,7]. The amount of water in the polymer matrix is at least 20% and can reach values of
99% by weight [9]. The design and preparation of hydrogels have significantly attracted
the attention of the biomedical community because of their physiochemical similarity
with the native extracellular matrix both compositionally and mechanically [8,10]. Unique
properties such as biodegradability, tunable chemical and three-dimensional physical
structure, good mechanical properties, high water content, and possible control over the
swelling kinetics [11] have offered great potential for the utilization of hydrogels in drug
delivery applications [12-15]. Their highly porous structure can easily be controlled by
changing the density of cross-links in the gel matrix and the affinity of the hydrogels for
the aqueous environment in which they are swollen. Their porosity also permits the
loading of drugs into the gel vehicle and subsequent drug release at a rate dependent on
the diffusion coefficient of the small molecule or macromolecule through the gel net-
work. Indeed, the advantages of using hydrogels for drug delivery may be largely phar-
macokinetic: specifically a depot formulation is created from which drugs slowly elute,
maintaining a high local concentration of drugs in surrounding tissues over an extended
period, although hydrogels can also be used for systemic delivery. Hydrogels are gener-
ally highly biocompatible, as reflected in their successful use in the peritoneum and
other sites in vivo . Biocompatibility is promoted by the high water content of hydrogels
and the physiochemical similarity of hydrogels to the native extracellular matrix, both
compositionally (particularly in the case of carbohydrate-based hydrogels) and mechan-
ically. Biodegradability or dissolution may be designed into hydrogels via enzymatic,
hydrolytic, or environmental pathways. However, degradation is not always desirable
depending on the timescale and location of the DDS. Hydrogels are also relatively
deformable and can conform to the shape of the surface to which they are applied. In the
latter context, the muco- or bioadhesive properties of some hydrogels can be advanta-
geous in immobilizing them at the site of application or in applying them on surfaces
that are not horizontal [10].
Moreover, hydrogels can be tailored into different shapes or geometries in terms of the
requirements of the drug release profile. For example, they can be formulated into slabs,
rods, nanoparticles, microspheres, membranes, sponges, films, and liquids [6,16].