Polysaccharides as Nanomaterials for Therapeutics - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 132

5.3.2 Polyelectrolyte Complexation (PEC)

Polyelectrolyte complexes (PEC) are formed by direct electrostatic
interactions of oppositely charged polyelectrolytes in solution (Figure
5.2C). PEC represents another biocompatible option for drug delivery
since no toxic covalent cross-linkers are used. These complexes
resemble ionic cross-linking since non-permanent networks
are formed that are more sensitive to changes in environmental
conditions [26]. However, unlike ionic cross-linking, in which ions or
ionic molecules react with the polyelectrolyte, in PEC the interaction
is between the polyelecrolyte and larger molecules with a broad MW
range [60]. The formation and stability of PEC is determined mainly
by the degree of interaction between the polyelectrolytes [49]. The
later is a factor of the charge density and distribution of each of the
oppositely charged polyelectrolyte. The chemical environment is also
crucial: The pH of the solution, the ionic strength, the temperature,
and the duration and mixing order. Secondary factors are the Mw of
the polyelectrolytes and their flexibility [26, 49, 60, 61]. The formed
interaction can be reinforced by ionic cross-linking [49, 62]. For
example, TPP and magnesium sulfate were used to stabilize PEC of
chitosan with gamma poly (glutamic acid) [63]. Positively charged
polysaccharides, namely chitosan, can form PEC with variety
negatively charged polymers such as the polysaccharides alginate,
dextran sulfate, chondroitin sulfate, hyaluronan, carboxymethyl
cellulose, carrageenan and heparin, peptides such as poly-g-glutamic
acid ,nucleic acid and synthetic polymers [49, 61, 64-66].

5.3.3 Self-Assembly

Upon grafting hydrophobic moieties onto a hydrophilic
polysaccharide an amphiphilic copolymer is created. In aqueous
solutions, amphiphilic copolymers tend to self-assemble into
nanoparticles in which the inner core is hydrophobic and the shell
is hydrophilic. The hydrophilic shell serves as a stabilizing interface
between the hydrophobic core and the external aqueous environment
(Figure 5.2D) [67]. This self-assembly is via hydrophobic interactions,
mainly in order to minimize interfacial free energy [61, 64]. The
formed nanoparticles are characterized by prolonged circulation
and thermodynamic stability [68]. In addition, since the core is
hydrophobic, these nanoparticles have been used for the delivery of