Biomedical Engineering Reference
In-Depth Information
of folic acid as a targeting ligand derives from fact that cancer cells
overexpress receptors for nutrients in order to maintain their fast-
growing metabolism [2] one of these receptor is folate receptor,
which is overexpressed in malignant cells including ovary, brain,
kidney, breast, colon, and lung [127]. Another advantage of using
nutrient receptors as targets is that they enable internalization of the
nanocarrier via receptor-mediated endocytosis. The activated drug
release was achieved by linking methotrexate to arabinogalactan
by an endosomally cleavable peptide Gly-Phe-Leu-Gly (GFLG). The
nanocarrier displayed significant cytotoxic activity to folate receptor
overexpressing cells in comparison with folate receptor-deficient
cells.
5.4.7 Pullulan-BasedNanoparticles
Pullulan has been demonstrated to self-assemble into nanoparticles
after modification by hydrophobic molecules, such as cholesterol
and stearic acid [128,129]. In addition, pullulan drug conjugated and
covalently cross-linked pullulan nanoparticles have been reported
[130,131]. Overall, pullulan-based nanoparticles have been used
for the delivery of proteins, anticancer drugs, imaging agents, and
nucleotides [69, 129, 130, 131].
Akiyoshi has been studying self-assembled nanoparticles of
cholesterol modified pullulan for more than a decade [69, 70,
129, 132-135]. The hydrophobized pullulan was shown to form
relatively monodisperse and colloidally stable nanoparticles (20-
30 nm) in water upon self-aggregation [132]. The self-assembled
nanoparticles demonstrated the ability to complex various
hydrophobic substances, including soluble proteins such as Insulin.
The complex between the nanoparticle and protein solution was
easily formed by simply mixing the two components [129]. The
particle size did not change after complexation with proteins [136].
The complexation with insulin occurred faster than with larger
proteins such as α-chymotrypsin or BSA. The nanoparticles showed
high colloidal stability and no dissociation of insulin or precipitation
were observed. The complexation contributed greatly to the
thermal stability of insulin (even after heating for 6 h at 90°C) and
protected insulin from enzymatic degradation. In vivo experiments
demonstrated preservation insulin's bioavailability [129]. The
ability of these nanoparticles to thermally stabilize proteins was
 
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