Enhancing Efficacy Through Polymer Science in PEGylated Drug Delivery

Abstract: PEGylation, the process of attaching polyethylene glycol (PEG) to therapeutic molecules, has transformed drug delivery by improving stability, solubility, and circulation time. This review explores the evolution, applications, and future directions of PEGylated drug delivery systems. We examined literature on PEG’s chemical properties, synthesis methods, therapeutic applications, and FDA-approved PEGylated products. PEGylation enhances pharmacokinetics and enables both passive and active tumor targeting. PEG’s unique chemical properties, including hydrophilicity, flexibility, and non-immunogenicity, make it an ideal candidate for conjugation with proteins, peptides, and small-molecule drugs. Various PEGylation strategies, including linear, branched, and sitespecific conjugation, have been developed to optimize therapeutic performance and reduce offtarget effects. The molecular weight and architecture of PEG can be precisely tuned to control drug release profiles and biodistribution. Additionally, PEG is widely used in nanoparticle surface modification, hydrogel formation, and liposomal formulations, demonstrating its adaptability across diverse drug delivery platforms. PEG prolongs drug half-life by reducing renal clearance and proteolytic degradation and facilitates passive tumor targeting through the enhanced permeability and retention (EPR) effect. Active targeting has also been achieved through PEGylated carriers functionalized with ligands for specific cell-surface receptors. Over 30 PEGylated drugs have been approved to date. PEG remains a cornerstone in nanomedicine, although new challenges highlight the need for innovative alternatives and conjugation techniques. The future of PEGylated drug delivery lies in smart, stimuli-responsive systems, integration with novel therapeutics, and the exploration of PEG alternatives that retain favorable properties while minimizing adverse immune responses.