Polysaccharides as Nanomaterials for Therapeutics - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 149

circulation of nanoparticle [151]. The heparin-modified poly(methyl
methacrylate) (PMMA) nanoparticles elongated the in vivo half-life
from only a few minutes to 5 h [151]. Dextran-coated nanoparticles
also demonstrated longer in vivo half-life but to a lesser extent in
comparison with heparin, probably since dextran has been shown
to activate the complement system [152]. In vitro , the heparin- or
dextran-coated nanoparticles were also demonstrated to be less
taken up by a macrophagic cell line in comparison with uncoated
nanoparticles [151]. The steric barrier formed by dense brush-like
arrangement of the attached polysaccharide chains could contribute
to the long-circulating properties of the heparin (or dextran)-coated
PMMA nanoparticles.
Recently, an artificial oxygen carrier based on a polysaccharide-
decorated nanoparticle was demonstrated [153]. The core-shell
nanoparticles, developed as red blood cell substitutes, were covered
with a long brush of polysaccharides (heparin, dextran, or dextran
sulfate) and demonstrated very low complement activation. The
nanoparticles were obtained by using a redox radical polymerization
mechanism in aqueous medium, which was followed by adsorption
or coupling of hemoglobin. Interestingly, a former heparin-coated
oxygen carrier developed by the same group demonstrated a
highly improved cell line tolerance in the presence of hemoglobin
[154]. In addition, the anticoagulant properties of heparin were
preserved upon coating the nanoparticles with heparin. When
benzene tetracarboxylic acid (BTCA) was used as a coupling agent
for hemoglobin to dextran-coated nanoparticles, the loading capacity
showed a 9.3-fold increase. The modification of nanoparticles by BTCA
slightly increased complement activation; however, this activation
was reverted by the further addition of hemoglobin. The bound
hemoglobin preserved its ability for exchanging oxygen [153].
5.6 Summary
The variety of naturally occurring polysaccharide properties has
been successfully utilized to create multiple nano-size drug delivery
systems. The advantages of polysaccharides enable the preparation
of nanocarriers for the delivery of proteins, peptides, antibiotics
and nucleic acids using several administration routes. In addition,
preliminary results from the first phase I clinical trial using a
polysaccharide nanocarrier for siRNA delivery have been presented.