Polysaccharides as Nanomaterials for Therapeutics - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 136

of aggregated shapes, their viscosity at concentration used for in vivo
delivery is very high and their solubility at a physiological pH is low
[84].
Chemical modification, usually by utilizing the primary amino
groups of chitosan, is another way to improve its physiochemical
properties. For example, conjugation of hydrophobic moieties
such as deoxycholic acid and cholesterol to chitosan allows solvent
induced self-assembly into nanoparticles [86, 87]. This principle
was used for preparation of 5β-cholanic acid (HGC)-modified glycol
chitosan nanoparticles for the delivery of the antiangiogenic peptide
RGD [88]. The RGD (Arg-Gly-Asp) peptides can specifically target
α v β 3 integrins on angiogenic endothelial cells and therefore inhibit
angiogenesis and tumor growth [89]; however, these peptides
have short half-life in vivo , and thus a delivery system is required.
The self-assembled polymeric nanoparticles of glycol chitosan
nanoparticles modified with hydrophobic bile acid analogs have
hydrophilic shells of glycol chitosan and hydrophobic cores of bile
acid derivatives. The hydrophobically modified glycol chitosan was
prepared by covalently attaching 5β-cholanic acid through amide
formation. The nanoparticles have a diameter of 230 nm and loading
efficiency >85%. The nanoparticles demonstrated prolonged and
sustained release and inhibition of HUVEC adhesion in vitro . In the
in vivo study, the RGD containing nanoparticles inhibited bFGF-
induced angiogenesis and significantly decreased tumor growth and
microvessel density in comparison with native RGD peptide. These
particles were previously used by the same group for gene delivery
and for the chemotherapeutic agents doxorubicin and paclitaxel [90,
91]. Other modifications of chitosan such as addition of thiol groups
and trimethylation can improve the mucoadhesive and permeation-
enhancing properties of chitosan [92]. Trimethylated chitosan
(TMC) is also characterized by increased solubility in neutral pH
[93]. Finally, targeted delivery of chitosan nanoparticles has been
achieved simply by conjugation of targeting ligand to chitosan for
example; nanoparticles containing galactosylated chitosan were
used for hepatic gene delivery [94]. In addition, folate-conjugated
chitosan nanoparticles were used for the delivery of interleukin-1
receptor antagonist (IL-1Ra) gene in rats with adjuvant induced
arthritis [95]. IL-1Ra is a natural blocker of the inflammatory cytokine
IL-1. When administered in vivo , the folate modified chitosan-DNA
nanoparticles off ered improved protection against inflammation