PEGylated molecules

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]. 

Polyethylene glycol (PEG) consists of repeating units of ethylene glycol forming linear or branched polymers with different molecular masses. Pegylation is the process by which PEG chains are covalently attached to lEN molecules. Pegylation confers a number of properties on lEN-a molecules, such as sustained blood levels that enhance antiviral effectiveness and reduce adverse reactions, as well as a longer half-life and improved patient compliance (Kozlowski et al. 2001). 

Table 3 Pharmacological parameters of pegylated IFN-a molecules approved for the treatment of chronic hepatitis C...

Other IFNs that can be used in the treatment of viral infections include IFN-P, IFN-m, a molecule that is more potent than its nonglycosylated form, which itself has activity comparable to that of IFN-a (Buckwold et al. 2007), and that will be delivered continuously by an implantable device, IFN-y and 1FN-A,1, a pegylated form of which will soon be available. 

Pegylated interferon is interferon that is attached to a polyethylene glycol molecule that increases the half-life of the drug, thus allowing once-weekly dosing versus thrice-weekly administration required for the unmodified formulation. Pegylated interferon is well tolerated and is superior in efficacy to unmodified interferon for the treatment of chronic hepatitis B.26... 

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...

Fee CJ (2007) Size comparison between proteins PEGylated with branched and linear poly (ethylene glycol) molecules. Biotechnol Bioeng 98 725-731... 

Figure 18.26 The branched PEGylation compound NHS-dPEG fmPEG h contains three mPEG arms, which provide an increased sphere of hydration around modified molecules compared to straight-chain PEGylation compounds.

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