Biomedical Engineering Reference
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a
Cleavable by stimuli
Lipid
Ligand PEG
b
Adhesion
to target cell
PEG cleavage
by stimuli
Membrane fusion
and drug release
Receptor
Fig. 9 Utility of de-PEGylation technology in liposomes. (a) PEG derivative possessing a lipid
moiety. The covalent bond between PEG and the lipid moiety can be cleaved by stimuli such as
those within the acid environment of cancer and inflammation. (b) After binding the target cell via
specific recognition of the receptor by the ligand, PEG molecules on the surface of the liposome
are cleaved. The release of PEG facilitates membrane fusion of the liposome and liposome
decomposition, resulting in efficient drug delivery
PEG (20 kDa) [ 43 ]. This demonstrates the strong hydrodynamic properties of
PEGylated molecules. The increase in hydrodynamic radius significantly decreases
renal clearance. Although the threshold of the molecular weight cut-off of renal
filtration of protein is about 65 kDa, the 30-kDa PEG demonstrates minimal renal
permeability [ 44 ].
3.2 Molecular Recognition of PEGylated Molecules
Although PEGylated molecules in the blood stream have longer half-lives than the
parent molecules, studies have reported conflicting conclusions about changes in
the binding affinities of PEGylated molecules. Chapman et al. demonstrated that
site-specific modification of antibody fragments at the termini of PEG diminishes
the loss of activity of the antibody fragment [ 45 ]. In contrast, Kubetzko et al.
reported a fivefold decrease in apparent affinity upon attachment of the 20-kDa
PEG molecule at the C-terminus of the antibody fragment [ 43 ]. By analyzing the
binding kinetics, they found that the reduction in affinity was mainly due to a slower
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