Li and coworkers reported glucoside- and pH-sensitive block copolymer
assemblies for the triggered release of insulin [118]. Triblock amphiphilic copolymer
poly(acrylic acid-co-acrylamidophenylboronic acid)-block-poly(2-acryloxyethyl
galactose)-block-poly(acrylic acid-co-acrylamidophenylboronic acid) {[(PAA-coPAAPBA)-b-] 2 PAEG} was synthesized using atom radical transfer polymerization,
which formed self-assembled structures with particles ranging from 230 to 270 nm.
The boronic acid polymer (PBA) of the block copolymer self-assemblies is responsible
for its glucose-sensitive nature through complexation with adjacent hydroxyl groups
of the carbohydrate moieties [119]. In vitro insulin binding studies revealed that the
profiles of NP micelles were dependent on both the pH and the glucose concentration.
The self-aggregated NPs of the block copolymer have been shown to release insulin
rapidly upon exposure to high concentrations of glucose.
11 Nanogels
Nanogels are colloidal solutions composed of crosslinked synthetic or biopolymer
networks. They have been synthesized with both chemically or physically associated
crosslinkages between the polymer networks. Recently, nanogels have attracted
major attention for the encapsulation and delivery of drugs and biomacromolecules
[120, 121]. Narian and coworkers reported the synthesis of carbohydrate-based
nanogels (118 and 119, Fig. 21) and studied their ability to encapsulate and deliver
biomacromolecules such as DNA, enzymes, or proteins in their active forms [122].
The size and morphologies of 118 and 119 were found to be thermoresponsive
and, at 37
C, nanogels have been obtained with diameters ranging from 30 to
40 nm. In biological studies, although nanogels 118 and 119 exhibited good
complexation properties with DNA, their gene transfection in Hep G2 cells was
found to be low. This was attributed to the high hydrophobicity and aggregation of
DNA–nanogel complexes. The incorporation of cationic polymer 120 onto the gels
led to an increase in cellular uptake and gene expression of DNA–nanogel
complexes. In the case of different sugars, the high activity of lactoside-coated
nanogels was thought to be due to their higher uptake by Hep G2 cells, which is
mediated by galactose–asialoglycoprotein receptor interactions as above. The
activity of the biomacromolecules, after encapsulation in cationic nanogels, was
studied with β-galactosidase. It was shown that the enzymatic activity remained after
complexation with the nanogels. In addition to monomolecular encapsulation,
cationic nanogels have also been used for bimolecular delivery applications. The
co-delivery of protein (BSA) and DNA in Hep G2 cells was successfully achieved
with these cationic nanogels.
Zhou and coworkers recently reported the synthesis of chitosan-based nanogels
and their pH-responsive biomedical applications [123]. Nanogels have been
prepared from chitosan and poly(methacrylic acid) (PMAA) polymers in two
ways: using covalent crosslinking or physical association between the polymers
(Fig. 22). Naturally occurring chitin, chitosan, and their derivatives have found
widespread applications in various biological settings [124].
330
N. Kottari et al.
assemblies for the triggered release of insulin [118]. Triblock amphiphilic copolymer
poly(acrylic acid-co-acrylamidophenylboronic acid)-block-poly(2-acryloxyethyl
galactose)-block-poly(acrylic acid-co-acrylamidophenylboronic acid) {[(PAA-coPAAPBA)-b-] 2 PAEG} was synthesized using atom radical transfer polymerization,
which formed self-assembled structures with particles ranging from 230 to 270 nm.
The boronic acid polymer (PBA) of the block copolymer self-assemblies is responsible
for its glucose-sensitive nature through complexation with adjacent hydroxyl groups
of the carbohydrate moieties [119]. In vitro insulin binding studies revealed that the
profiles of NP micelles were dependent on both the pH and the glucose concentration.
The self-aggregated NPs of the block copolymer have been shown to release insulin
rapidly upon exposure to high concentrations of glucose.
11 Nanogels
Nanogels are colloidal solutions composed of crosslinked synthetic or biopolymer
networks. They have been synthesized with both chemically or physically associated
crosslinkages between the polymer networks. Recently, nanogels have attracted
major attention for the encapsulation and delivery of drugs and biomacromolecules
[120, 121]. Narian and coworkers reported the synthesis of carbohydrate-based
nanogels (118 and 119, Fig. 21) and studied their ability to encapsulate and deliver
biomacromolecules such as DNA, enzymes, or proteins in their active forms [122].
The size and morphologies of 118 and 119 were found to be thermoresponsive
and, at 37
C, nanogels have been obtained with diameters ranging from 30 to
40 nm. In biological studies, although nanogels 118 and 119 exhibited good
complexation properties with DNA, their gene transfection in Hep G2 cells was
found to be low. This was attributed to the high hydrophobicity and aggregation of
DNA–nanogel complexes. The incorporation of cationic polymer 120 onto the gels
led to an increase in cellular uptake and gene expression of DNA–nanogel
complexes. In the case of different sugars, the high activity of lactoside-coated
nanogels was thought to be due to their higher uptake by Hep G2 cells, which is
mediated by galactose–asialoglycoprotein receptor interactions as above. The
activity of the biomacromolecules, after encapsulation in cationic nanogels, was
studied with β-galactosidase. It was shown that the enzymatic activity remained after
complexation with the nanogels. In addition to monomolecular encapsulation,
cationic nanogels have also been used for bimolecular delivery applications. The
co-delivery of protein (BSA) and DNA in Hep G2 cells was successfully achieved
with these cationic nanogels.
Zhou and coworkers recently reported the synthesis of chitosan-based nanogels
and their pH-responsive biomedical applications [123]. Nanogels have been
prepared from chitosan and poly(methacrylic acid) (PMAA) polymers in two
ways: using covalent crosslinking or physical association between the polymers
(Fig. 22). Naturally occurring chitin, chitosan, and their derivatives have found
widespread applications in various biological settings [124].
330
N. Kottari et al.