Biomedical Engineering Reference
In-Depth Information
hydrophobic drugs. Several properties such as size, surface charge,
loading efficiency, stability, and biodistribution can be altered for
a particular application. For example, the size of the nanoparticles
can be controlled by adjusting the length of the hydrophobic moiety
and the length of the polymer [67]. Scaling relations for this purpose
have been developed [67]. In addition, the surface charge, which
aff ects particle serum stability and cellular uptake, can be altered by
controlling the degree of substitution, the length of the hydrophobic
moiety or the nature of the hydrophobic moiety [61, 69]. For example,
a cationic derivatization of the hydrophobic moiety has been used
to promote cellular uptake [70]: amine bearing cholesterol but not
cholesterol without an amine, demonstrated protein cellular delivery
when grafted onto pullulan to create self-assembled nanoparticles
[70].
Polysaccharides can be modified with a wide range of hydrophobic
moieties among them bile acids (e.g., 5β-cholanic acid, cholic acid
and deoxycholic acid), fatty acids (e.g., palmitoyl acid, stearic acid,
oleic acid) [61], cholesterol, and hydrophobic drugs.
5.4 Polysaccharide-BasedNanoparticles
5.4.1 Chitosan-BasedNanoparticles
Chitosan's nature and the ease of chemical modifications enable
multiple nanoparticle preparation schemes among them: covalent
cross-linking, ionic cross-linking, polyelectrolyte complexation,
desolvation, and self-assembly [71].
Early works describing chitosan nanoparticles for drug
delivery were based on covalently crossing chitosan with
glutaraldehyde [50]. However, since glutaraldehyde is highly toxic,
biocompatible alternatives for covalent cross-linking have been
developed, such as condensation reactions with 1-ethyl-3-[3-
dimethylaminopropyl]carbodiimide hydrochloride, which was used
to facilitate intramolecular cross-linking of chitosan by natural di-
and tricarboxylic acids [52]. This method allows the formation of
polycations, polyanions, and polyampholyte nanoparticles.
Since chitosan is positively charged, ionic cross-linked
nanoparticles can be prepared using polyanions; among them the
most widely used is tripolyphosphate (TPP). The wide use of TPP
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