Polysaccharides as Nanomaterials for Therapeutics - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 129

5.2.8 Heparin

Heparin is a linear glycosaminoglycan (GAG) composed of repeating
disaccharide units of 1,4-linked uronic acid (D-glucuronic (GlcAor
l-iduronic acid (IdoA) and D-glucosamine (GlcN) (Figure 5.1). The
uronic acid usually comprises 90 percent l-idopyranosyluronic acid
(l-iduronic acid, IdoA) and 10 percent D-glucopyranosyluronic acid
(D-glucuronic acid, GlcA). In addition, there are structural variations
at the disaccharide level [46]. Due to high content of sulfo and
carboxyl groups, heparin has the highest negative charge density
of any known biological molecule [46]. The Mw of heparin varies
between 5-40 kDa and it is extracted mainly from mucosal tissues
of porcine and bovine [46]. Clinically, heparin has been used as an
anticoagulant since the 1930s [46]. The anticoagulant activity of
heparin requires direct interaction with the serine protease inhibitor
antithrombin III, which causes a conformational change that allows
antithrombin III to inhibit thrombin and other serine proteases
within the coagulation cascade [47]. Heparin is produced exclusively
by mast cells (as opposed to the structurally related GAG heparan
sulphate) [23]. Beyond its anticoagulant activity, heparin has been
shown to have antiviral activity and ability to inhibit complement
activation, tumor growth and angiogenesis [47].

5.3 Main Mechanisms of Nanoparticle

Preparation from Polysaccharides

5.3.1 Cross-Linking

In cross-linked nanoparticles, the polymeric chains are interconnected
by cross-linkers, leading to the formation of a 3D network (Figure
5.2A,B) [48]. The main factor that determines the properties of
a cross-linked nanoparticle such as drug release and mechanical
strength is the cross-linking density, which is determined by the
molar ratio between the cross-linker and the polymer repeating units
[48]. There are two types of cross-linked nanoparticles determined
by the nature of the cross-linking agents: covalently cross-linked
nanoparticles and ionically cross-linked nanoparticles.