Improvement of drug delivery by covalent modification with polyethylene
glycol (PEG) has been widely applied to proteins and low molecular weight
pharmaceuticals. Protein therapeutic agents have the drawback of short circulating
half-life due to their lability towards proteolytic enzymes and rapid clearance by kidney
filtration. Moreover, their recognition by the immune system results in the production
of neutralizing antibodies. Several strategies have been used for the PEGylation of
proteins at the amino group of lysine but the product is heterogeneous due to random
PEGylation. More recently, selective PEGylation of proteins was achieved by
introduction of a PEGylated carbohydrate in an O-glycosylation site. This technique is
called glycoPEGylation and is used for the production of several therapeutics, some of
them are currently in advanced clinical trials. Improvement of the delivery system
rather than the drug itself has led to the optimization of the therapeutic properties of
existing drugs by minimizing their side effects. In this respect, active targeting to
receptors present in cancer tissues prevents healthy ones from being damaged. Since
carbohydrates have been recognized as playing an important role in the interaction with
cell receptors, PEGylated carbohydrates have been used for active targeting of drugs. In
this review we discuss different applications of sugar-PEGylation.
Keywords: Active targeting, Bioavailability, Carbohydrates, Chemotherapy,
Drug carriers, Drug delivery, Gene delivery, Gene therapy, Glycan delivery,
GlycoPEGylation, Ligands, Multiarm PEGs, O-GlcNAc quantification, PEG,
PEG-sialic acid, PEGylated nanoparticles, PEGylated polysaccharides, PEGylation, siRNA, Sugar PEGylation, Targeted delivery.
