Biomedical Engineering Reference
In-Depth Information
blood circulation, and gradually accumulated specifically at a liver tumor. The high
tumor/liver imaging ratio was due to the enhanced permeability and retention
(EPR) effect [
244
,
245
] of lactosomes.
6 Nanogels
Nanogels are nanometer-sized hydrogel nanoparticles (less than about 100 nm)
with three-dimensional networks of physically crosslinked polymer chains. They
have attracted growing interest over the last decade because of their potential for
applications in biomedical fields, such as DDS and bioimaging [
246
-
249
].
Physically crosslinked nanogels can be prepared using noncovalent interactions
between polymer chains, such as hydrogen bonds, van der Waals forces, and electro-
static and hydrophobic interactions. It is generally well known that the preparation of
stable physically crosslinked nanogels with controlled sizes using such associating
polymers is difficult because of their relatively weak noncovalent interactions.
Akiyoshi and coworkers proposed a self-assembling strategy for the preparation of
physically crosslinked nanogels using the controlled association of hydrophobically
modified polymers in dilute aqueous solution [
250
]. In fact, cholesterol-modified
polysaccharides such as cholesterol-pullulan (CHP) formed stable monodispersive
nanogels with a diameter of about 30 nm in water. This result suggests that the
association of cholesteryl groups provides crosslinking points through hydrophobic
interactions.
Physically crosslinked nanogels have been reported in various combinations
such as cholesterol-bearing poly(amino acids) [
251
], cholesterol-bearing mannan
[
252
], deoxycholic acid-bearing chitosan [
253
], bile acid-bearing Dex [
254
], syn-
thetic polyelectrolytes with hydrophobic groups [
255
], and alkyl group-modified
poly(
N
-isopropylacrylamide)-cholesterol-modified polysaccharide mixtures [
256
].
Physically crosslinked nanogels have advantages with respect to their biomedical
applications because there is no need to use crosslinkers and/or catalysts, which
may be toxic, and there are no byproducts in the preparation process.
Recently, Akiyoshi and coworker reported that lipase from
Pseudomonas
cepacia
and the CHP nanogel were spontaneously complexed by simply mixing,
leading to increased enzymatic activity after complexation. The complexation also
led to a substantial increase in the thermal stability of the lipase (Fig.
13
). This is a
new type of nano-encapsulation of enzyme inside a hydrogel matrix. This simple
and effective method is useful in enzyme engineering and bioengineering [
257
].
Akiyoshi et al. also proposed cholesterol group-modified enzymatically synthesized
glycogen (CHESG) nanogels with approximately 35 nm in diameter, which were
formed via a number of hydrophobic domains as physical crosslinking segments
(Fig.
14
). It was possible to provide strong complexation with a number of proteins,
and high chaperone-like activity was seen for thermal stabilization of enzymes by
CHESG-CD supramolecular systems. These functions are valuable for protein
delivery systems [
258
].
