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Polyethylene glycol is a compound with emerging applications which are engineered multi-functional nanoparticles as pharmaceutical drug carriers in clinical technology (1). Coating the surface of nanoparticles with polyethylene glycol (PEG), or “PEGylation”, is a commonly used approach for improving the efficiency of drug and gene delivery to target cells and tissues (2). Potential approaches were sought to overcome these constraints which led to evolution of PEGylation as a strategy to impart favorable pharmacokinetic and pharmacodynamic properties to therapeutics. PEGylation involves modification of the therapeutics by linking one or more polyethylene glycol (PEG) molecules to it. Polyethylene glycol, a polymer of ethylene oxide monomers, being safe and non-toxic, has been approved by FDA for human use. Till date, researchers described a number of different approaches for PEGylation. The first generation of PEGylated products largely involved the nonspecific and irreversible PEGylation of target proteins with linear PEG chains. The demand for bio-responsive drug delivery systems led to the development of second generation PEGylated products, having covalently bound branched PEG chains at specific positions of the molecule (3).

Treatment for cancer therapy like chemotherapy lacks specificity in targeting cancer cells over the normal cells. It leads to severe side effects and suboptimal therapeutic efficacy. To achieve selective tumor accumulation via the leaky vasculature, the surface of nanoparticles is typically modified with hydrophilic polymers such as polyethylene glycol (PEG) (4).

It is the most commonly used protective coating material for drug delivery liposomes (DDLs) and nanoparticles, and has also providedthe same protection as a covalently bound conjugate to proteins (5). PEG is extensively used as a surface modifier of particulate drug carriers to provide important biological properties such as reducing toxicity and extending circulation time. However, only a few nano carrier platforms based on PEGylated particles have reached the market with, in several cases, limited improvements over already available formulations. PEG and PEG monomethyl ether are ones of the few polymers approved for internal use in humans by the FDA, which is an important consideration when developing new pharmaceutical formulations (6).

 In PEGylation, linear PEGs are the simplest and most often used conjugate agents. In these cases, active small molecules are conjugated to the distal ends of a PEG carrier. Herein PEG delivery systems are distinguished by therapeutic application (anti-tumor, anti-inflammatory, etc.) and their corresponding PEGylated small molecules (7).

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