Biomedical Engineering Reference
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Scheme 3 Releasable PEGylation based on 1,6-benzyl elimination prodrug strategy
Scheme 4 Releasable
PEGylation based on the
b -elimination reaction
response called the accelerated blood clearance phenomenon (ABC phenomenon),
in which the circulation time of a second dose of injected PEGylated liposome is
substantially reduced [ 40 , 41 ]. Harashima et al. developed a multifunctional enve-
lope-type nanodevice (MEND) for a nonviral gene delivery system [ 39 , 42 ]. In this
system, multiple device functions are assembled into a single system. In particular,
PEGs on the surface of liposomes were designed to be cleaved by enzymes such as
matrix metalloproteinases (MMPs) that are specifically expressed at tumor sites.
Removing PEGs resulted in an improvement of cellular uptake and subsequent
endosomal escape of the liposome.
3 Effect of PEGylation on Pharmaceuticals
3.1 Reduction of Renal Clearance
One of the remarkable properties of PEGylation is to increase the hydrodynamic
radius in order to decrease renal clearance. For example, Kubetzko et al. have
reported that antibody fragments (theoretically 29 kDa) showed retention volumes
corresponding to a size range of 200-300 kDa by SEC upon mono-PEGylation with
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