Biomedical Engineering Reference
In-Depth Information
Fig. 8 Examples of heterobifunctional PEGs popularly used for PEGylation
To date, a variety of heterobifunctional PEGs have been reported. Some popular
derivatives are shown in Fig.
8
. Several PEG derivatives are now commercially
available from NOF, Japan.
2.4 Linear and Branched PEGs
Early PEGylation technology utilized linear PEG chains for conjugation. As stated
above, multiple and nonspecific conjugations often change the activity of native
proteins significantly, and it has been reported that the large molecular weight of
PEG causes a tendency to accumulate in the liver [
22
]. Branched PEG derivatives
are effective candidates for solving these issues. The same PEGylation effect on a
pharmaceutical can be obtained by introducing a smaller branched PEG with fewer
conjugation points. The second generation of PEGylation technology often utilized
branched PEGs because branched PEGylated products circulate longer in the blood
than linear PEGylated products [
23
]. This effect is thought to be because of the
steric hindrance of branched PEG [
24
]. PEGylation with branched-chain PEG has
been adopted in the development of FDA-approved drugs, including PEGASYS
[
25
], Macugen [
26
], and Cimzia [
27
].
Size-exclusion chromatography (SEC) showed no significant difference in size
between branched and linear PEGylated proteins [
28
]. Therefore, the longer in vivo
half-life of branched PEGylated drugs was not due to the size of the conjugate in
solution, but probably to the more effective masking of the protein surface by
branched PEGs.
