Biomedical Engineering Reference
In-Depth Information
O
HO
OH
n
O
Poly(ethylene glycol)
(PEG)
O
O
O
O
H
3
C
Succinic anhydride
OH
O
H
3
C
O
OH
O
O
n
O
Monomethoxy-poly (ethylene glycol)
(mPEG)
Succinylated mPEG
O
HO N
N
-hydroxy-succinimide
(NHS)
O
O
O
O
O
H
3
C
N
O
O
n
O
O
Succinimidyl succinate (SS)-mPEG
Protein
NH
3
O
HO
N
O
O
Protein
O
NH
H
3
C
O
O
O
PEGylated protein
Figure 11.17
Schematic representation of conjugation reaction between
N
-hydroxy-
succinimide (NHS) derivative of methoxy PEG and protein.
length and shape
[391]
, and that can translate not only to improve efficacy but also
to reduce dosing frequency and increase patient compliance. All these improvements
result from size enlargement, protein surface and glycosylation function masking,
charge modification, and epitope shielding of PEG-protein conjugate. Generally, the
longer the PEG chain, the longer the elimination half-life of the PEG-protein conju-
gates
[391,392]
.
Research in the field of PEGylated proteins and peptides has provided data about
prolonged circulation and increased half-life (
t
1/2
) of many PEGylated proteins and
peptides as compared to their respective parent drug. Some values of
t
1/2
of PEGylated
P/P drugs are mentioned here from the original research articles and compared with
t
1/2
of parent drugs. For example,
t
1/2
of PEG-GCSF was found to be 7 h (parent drug
t
1/2
is 1.8 h);
t
1/2
of PEG-IFN-2a was found to be 51 h (parent drug
t
1/2
is 0.7 h); t
1/2
of PEG-SOD was found to be 38 h (parent drug
t
1/2
is 0.01 h);
t
1/2
of PEG uricase was
found to be 72 h (parent drug
t
1/2
is 3 h);
t
1/2
of PEG-interleukin-6 was found to be 48 h
(parent drug
t
1/2
is 0.05 h);
t
1/2
of PEG-arginine deiminase was found to be 50 h (par-
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