Biomedical Engineering Reference
In-Depth Information
investigated further [133]. The molecular chaperon-like activity
was demonstrated on proteins using a system consisting of the
cholesterol-pullulan nanoparticles and β-cyclodextrin. Capture of
heat-denatured unfolded protein and the release of the refolded
form were achieved and the irreversible protein aggregation upon
heating was completely prevented, recovering almost 100% of
protein activity. Intracellular protein delivery by self-assembled
nanoparticles of cationic cholesteryl group-bearing pullulans
was also demonstrated [69]. While particle size did not change
significantly upon replacing the cholesterol with the cationic
cholesteryl group, the zeta potential became positive (+7.7 ± 0.1 mV
in comparison with −1.3 ± 0.4). In addition, the binding constant to
the model protein, BSA, significantly grew. The cholesteryl-pullulan
nanoparticles demonstrated a more eff ective internalization of
protein to into HeLa cells in comparison with cationic liposomes
and a protein transduction domain (PTD)-based carrier. Upon cell
internalization, the protein-containing nanoparticle dissociated
and the protein was released. Recently, cholesteryl-pullulan
nanoparticles were used as an antigenic protein delivery system for
adjuvant-free intranasal vaccines [70]. Intranasal delivery of a non-
toxic subunit fragment of Clostridium botulinum type-A neurotoxin
using these nanoparticles induced vigorous botulinum-neurotoxin-
A-neutralizing serum IgG and secretory IgA antibody responses.
In addition, intranasally immunization of tetanus toxoid with the
nanoparticles induced strong tetanus-toxoid-specific systemic and
mucosal immune responses.
5.5 Polysaccharide-CoatedNanoparticles
Surface modification of nanoparticles with polysaccharides, an
outcome of the cell surface polysaccharide discovery, has remarkable
advantages for drug delivery systems: It endows the nanoparticle
with long-term circulation and increased stability. In addition, it
provides targeting abilities: pullulan coating have been used for
hepatic delivery [137], alginate and chitosan coating have been used
for mucosal delivery [138], mannan coating facilitated uptake by
macrophages [139] and HA-coated nanoparticles have been used to
target CD44 overexpressing cells [3, 140, 141]. Another advantage is
cryoprotection, which has been reported for several polysaccharides
 
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