Influence of polyglycerol versus polyethylene glycol coatings on the physicochemical properties and biological performance of liposomes

In recent years, polyglycerol (PG) has received much attention as an alternative to polyethylene glycol (PEG) with adequate biocompatibility and multifunctionality. However, systematic studies comparing the effects of PG- and PEG- coatings on liposomal properties are still lacking, which might provide more insights into their capacity for drug delivery. In this study, polyglycerol (10) stearate (PG-10-MS) was compared with polyethylene glycol (20) stearate (PEG-20-MS) in terms of how these two types of polymeric modifications influenced the physicochemical properties and biological functions of liposomes, with identical hydrophobic anchoring groups and comparable molecular weights for the polymeric moieties. The results demonstrated that both PEGylated and PGylated liposomes possessed excellent physical stability, reduced macrophage uptake in vitro, and prolonged circulation half-life in vivo. Although both polymers conferred hydrophilicity to the liposome surface, they exerted opposing effects on lipid membrane fluidity. On the other hand, PGylated liposomes exhibited superior erythrocyte compatibility, and cytotoxicity was relatively low. Following drug loading, both liposomal formulations showed comparable antitumor efficacy in vitro and in vivo. Collectively, these findings indicated that PGylation showed even superior blood compatibility and comparable drug delivery efficacy to PEGylation, underscoring the potential of PG-based polymers as viable alternatives to PEG.