Polysaccharides as Nanomaterials for Therapeutics - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 126

variable and can consist of homopolymeric blocks and alternating M
and G residues [19]. The composition, sequence, and molecular weight
determine the physical properties of alginate [20]. Alginates are
extracted mainly from brown algae and acetylated forms of alginate
can be isolated from the bacteria Pseudomonas and Azotobacter [20].
As a polymer for drug delivery purposes, alginate possesses
several attractive properties: It is biocompatible, non-toxic,
and water soluble and has the highest mucoadhesive strength
compared with other natural polysaccharides such as chitosan and
carboxymethylcellulose [21, 22].
5.2.3 Hyaluronan
Hyaluronan (HA) is a linear high-Mw glycosaminoglycan (GAG)
composed of alternating disaccharide units of D-glucuronic acid
and N -acetyl-D-glucosamine with β-(1 , 4) interglycosidic linkage
[23] (Figure 5.1). Hyaluronan possesses remarkable hydrodynamic
properties, especially related to its viscosity and ability to retain
water [24]. It was previously regarded important mostly for joint
lubrication or organ structural stability [24]. However, HA was found
to be essential for proper cell growth, embryonic development,
healing processes, inflammation, and tumor development [24, 25].
As opposed to other GAGs, HA is not sulfated, not linked to a protein
and naturally produced by bacteria as a capsule [23]. Commercially
available HA is either produced through bacterial fermentation of
Streptococcus species or extracted from rooster combs, umbilical
cords, synovial fluids, or vitreous humor [26]. However, HA obtained
from these production methods is usually very polydispersed;
therefore, a method to produce HA of a defined size has also been
developed [27, 28].
There are several advantages of HA that make it suitable for drug
delivery: It is water soluble, biodegradable, biocompatible, non-
toxic, and non-immunogenic and can be easily chemically modified
[29, 30]. In addition, it is the major ligand for CD44 and RHAMM
(CD168) and therefore is suitable for targeting CD44 and RHAMM-
expressing cells [25, 31]. CD44 and CD168 are overexpressed by
various tumors, for example, squamous cell carcinoma , ovarian,
colon, stomach, glioma, and many types of leukemia , lymphoma, and
myeloma [32-34], which makes the use of HA as a targeting agent
even more attractive.