Biomedical Engineering Reference
In-Depth Information
water [
195
]. Mikhail and Allen prepared PEG-
b
-PCL covalently attached to
docetaxel and investigated the morphology of the self-assembled structure. They
reported the release behavior of the drug from the micelles, comparing with block
copolymer micelles physically entrapping docetaxel [
196
]. Ding et al. synthesized
PEG-
b
-PLA having protoporphyrin IX residues at its terminal, and investigated the
micelle formation and its application to photodynamic therapy [
197
]. Hedrick et al.
reported a block copolymer of PEG and PTMC having polar side-chain groups and
investigated the effect of intramicelle hydrogen bonding on the stability of polymer
micelles, their drug loading efficiency, and the cytotoxic activity of the drug-loaded
polymer micelles [
198
].
Of course, many other hydrophilic polymers have been used as outer shell-forming
segments in polymer micelle systems. This review focuses on polymer micelle
systems using biodegradable polymers for both core-forming and shell-forming
segments. Researches on the polymer micelles formed by combination of aliphatic
polyesters and nonbiodegradable hydrophilic polymers have been reviewed in the
literature [
16
]. Sun et al. synthesized Dex-
b
-PCL by disulfide bond formation [
146
].
They reported the micelle formation of the block copolymer and efficient intracellular
drug release by cleavage of the disulfide bond under the reductive conditions of the
cytosol. Nottelet et al. reported the preparation of fully biodegradable polymer
micelles of block copolymers of carboxylic acid-functionalized PLA and PLA [
89
].
Wang et al. reported the micelle and vesicle formation of polyphosphate-
b
-PCL and
their potential utility as cellular delivery vehicles for anticancer drugs [
199
]. Liu et al.
also reported a polymer micelle system of star-shaped polyphosphate-
b
-PLA having
disulfide linkages, and its efficient cellular delivery of DXR [
200
]. Ouchi et al.
reported use of PDP having amino or carboxylic acid groups as hydrophilic segments
for formation of biodegradable micelles [
138
,
139
]. They reported the entrapment and
release behavior of DXR from polymer micelles composed of PDP-
b
-PLA. We
reported the preparation of negatively charged biodegradable polymeric micelles
consisting of polypeptide-
b
-PLA (PAsp-
b
-PLLA) [
142
,
143
].
The advantages of polymer micelles are their small size and core-shell structure,
which protects bioactive agents entrapped in the core by a hydrophilic polymer
shell. Such polymeric micelles can escape rapid renal excretion, and display long
circulation times after administration in the body. However, all physically assem-
bled polymeric micelles have a drawback of easy dissociation in the body fluids
because of instability under extremely diluted conditions below the critical micelle
concentration (CMC). Such a dissociation behavior leads to unfavorably rapid
release of the bioactive agents and interferes with site-specific transport of the
micelles to a target site. We reported the preparation of polyanion-coated
biodegradable polymeric micelles by coating positively charged polymeric
micelles consisting of poly(
L
-lysine)-
block
-poly(
L
-lactide) (PLys-
b
-PLLA) AB
diblock copolymers with anionic hyaluronic acid (HA) by polyion complex (PIC)
formation. The obtained HA-coated micelles showed significantly higher stability
in aqueous solution (Fig.
9
)[
201
]. The HA-coated micelles showed sustained
release of model drugs and low cytotoxicity. It is known that there are receptors
for HA on liver sinusoidal endothelial cells (LSECs). Specific interactions of
