Biomedical Engineering Reference
In-Depth Information
clinically important proteins, including human growth hormone and interleukin-2,
have been PEGylated using TGase [
14
].
2.3 Heterobifunctional PEG
Heterobifunctional PEG, which possesses different functional groups at the
a
- and
o
-chain ends, is very useful in the field of drug delivery [
15
]. For example,
heterobifunctional PEG can conjugate drug-containing nanoparticles with a
targeting ligand (Fig.
6
). In one study, a method for the synthesis of heterobi-
functional PEG by direct ring-opening polymerization of ethylene oxide (EO) using
a metal alkoxide initiator with a protected functional group was developed (Fig.
7
)
[
16
,
17
]. This useful method was further developed by Akiyama et al., [
18
-
21
].
Targeting ligand
PEG
Fig. 6 Utility of the
heterobifunctional PEG. Two
different components such as
drug and ligand can be
introduced at the different
ends of PEG
Small drug, protein,
nanoparticle
Fig. 7 Synthesis of heterobifunctional PEG. (a) Nagasaki et al. developed a method for the
polymerization of EO using an initiator containing defined functionalities [
16
,
17
]. (b) Akiyama
et al. further developed a synthetic route to prepare a series of heterobifunctional PEGs [
18
-
21
].
After the ring-opening polymerization of ethylene oxide, a second functional group was
introduced at the
o
-end of PEG
