Polysaccharides as Nanomaterials for Therapeutics - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 140

percent of grafted PLGA. In vitro , the micelles exhibited higher cellular
uptake and greater cytotoxicity in comparison with free doxorubicin
for CD44 over-expressing cells (HCT-116) suggesting that they were
taken up by the cells via HA receptor-mediated endocytosis [111]. The
same group has recently prepared self-assembled HA nanoparticles
for the delivery of paclitaxel by grafting an amine-terminated
hydrotropic oligomer onto HA [112]. Active tumor targeting by self-
assembled HA-5β-cholanic acid nanoparticles has also been shown
[113]. Particle size could be controlled in the range of 240-430 nm by
varying the degree of substitution of the hydrophobic moiety. In vitro ,
fluorescently labeled Cy5.5-HA-nanoparticles were detected in the
cytosol of CD44 overexpressing cells (SCC7) to a much greater extent
than cells with low CD44 expression (CV-1). When administered
systemically to tumor-bearing mice, the nanoparticles were shown
to selectively accumulate in tumor sites. Smaller HA-NPs were able
to reach the tumor site more eff ectively than larger HA-NPs. In
addition, the concentration of the nanoparticles in the tumor site
was dramatically reduced when mice were pretreated with free HA.
This suggests an additional active targeting mechanism, beyond the
passive targeting of the EPR eff ect.
5.4.4 Dextran-BasedNanoparticles
Several strategies have been reported for dextran-based nanoparticles
among them dextran-drug conjugates and self-assembly of
hydrophobically modified dextran [114, 115]. The cardiotoxicity of
doxorubicin can be significantly reduced by conjugation to dextran
and followed by encapsulation in chitosan nanoparticle [116]. Upon
conjugation of poorly water-soluble drugs to dextran, hydrophobic
derivatives that self-assemble into nanoparticles are formed [117].
The self-assembled nanoparticles were shown to have high loading
efficiency. Particle size was strongly influenced by the degree of
dextran modification and preparation technique.
Dextran sulfate-based nanoparticles have been mostly
prepared by PEC, exploiting the anionic nature of dextran sulfate
for electrostatic interaction with positively charged polycations
(for example, chitosan and polyethylenimine.) Huang et al. [118]
prepared chitosan-dextran sulfate PEC for the controlled release
of vascular endothelial growth factor (VEGF). VEGF, a growth factor
that stimulates angiogenesis and therefore desired as a therapeutic