Biomedical Engineering Reference
In-Depth Information
AB-type diblock copolymers of PDP and polyester can be synthesized by two-
step polymerization using a basically similar strategy to that outlined above. After
first step polymerizaiton to obtain a polymer with terminal hydroxyl group, the
hydroxyl group on the terminal can be used as initiating group for second step
polymerization to give an AB-type diblock copolymer. Ouchi et al. synthesized
amphiphilic AB-type diblock copolymers of PLA and PDP with reactive side-chain
groups [
138
-
140
]. They also reported the preparation of polymer micelles using the
PDP-
b
-PLA [poly(Glc-Lys)-
b
-PLA] [
138
,
139
].
Several polypeptides possess pendent functional groups, including carboxylic
acid (
COOH), thiol (
SH), and amine (
NH
2
). These functional groups are
further utilized for bioconjugation and shell-crosslinking of polymer micelles.
A facile method for preparation of polypeptide-
b
-polyester is ROP of NCAs
using primary amino group-terminated polyester. We reported on the preparation
of AB-type polypeptide-
b
-PLA containing Asp residues with a reactive carboxylic
acid group using amino-terminated PLA (NH
2
-PLA) [
141
] and the subsequent
formation of polymer micelles with a positively charged shell [
142
,
143
].
Polysaccharides are hydrophilic natural polymers that can be degraded enzymati-
cally. Block copolymers containing polysaccharide as a block were reviewed recently
[
144
]. The synthesis of block copolymers of polysaccharides and aliphatic polyesters
has also been tried. But, many successful results were not reported because the
reactivity of many hydroxyl groups on polysaccharides was an obstacle to the ROP
of cyclic polyester or coupling reactions using terminal-activated polysaccharides.
Li and Zhang reported the synthesis of maltoheptaose-
b
-PCL copolymers by ROP
[
145
]. Even though the short oligosaccharide segment made of seven units may
not be considered as a true polymer chain, the chemistry devised by them should
be easily applicable to longer saccharidic chains. Liu and Zhang used the Michael
reaction for coupling a dextran (Dex) with an amino-functionalized terminal and
acrylolyl end-capped PCL [
146
]. Sun et al. also synthesized Dex-
b
-PCL by disulfide
bond formation [
147
].
Some other degradable (i.e., nonvinyl-type) polymers have been reported as
components for amphiphilic block copolymers. For example, Hsiue reported the
synthesis of a block copolymer of poly(2-ethyl oxazoline) and PLA by ROP. They
reported the use of ABA-type triblock copolymers as pH-responsive polymer
micelles [
148
].
Many kinds of nonbiodegradable vinyl-type hydrophilic polymers were also used
in combination with aliphatic polyesters to prepare amphiphilic block copolymers.
Two typical examples of the vinyl-polymers used are poly(
N
-isopropylacrylamide)
(PNIPAAm) [
149
-
152
] and poly(2-methacryloyloxyethyl phosphorylcholine)
(PMPC) [
153
]. PNIPAAm is well known as a temperature-responsive polymer and
has been used in biomedicine to provide smart materials. Temperature-responsive
nanoparticles or polymer micelles could be prepared using PNIPAAm-
b
-PLA block
copolymers [
149
-
152
]. PMPC is also a well-known biocompatible polymer that
suppresses protein adsorption and platelet adhesion, and has been used as the
hydrophilic outer shell of polymer micelles consisting of a block copolymer of
PMPC-
co
-PLA [
153
]. Many other vinyl-type polymers used for PLA-based amphi-
philic block copolymers were also introduced in a recent review [
16
].
