The Art of PEGylation: From Simple Polymer to Sophisticated Drug Delivery System.

The development of effective drug delivery systems (DDSs) is important for cancer and infectious disease treatment to overcome low bioavailability, rapid clearance and the toxicity of the therapeutic towards non-targeted healthy tissues. This review discusses how PEGylation, the attachment of poly(ethylene glycol) (PEG) molecules to nanoparticles (NPs), enhances drug pharmacokinetics by creating a "stealth effect". We provide the synthesis methods for several PEG derivatives, their conjugation with NPs, proteins and characterization using modern analytical tools. This paper focuses particularly on covalent conjugation and self-assembly strategies for successful PEGylation and discusses the influence of PEG chain length, density and conformation on drug delivery efficiency. Despite the PEGylation benefits, there are several challenges associated with it, including immunogenicity and reduced therapeutic efficacy due to accelerated blood clearance. Therefore, the balance between PEGylation benefits and its immunogenic risks remains a critical area of investigation.