Influence of polyethylene glycol coating of different molecular weights and densities on liposome properties

Abstract

PEG remains a central focus of numerous preclinical and clinical studies owing to its distinctive advantages. Notably, the molecular weight of PEG and its modification density are critical factors influencing PEGylated nano drug delivery systems; however, this area remains inadequately explored. In this study, we assessed the effects of different PEG molecular weights (1000, 2000, 5000, and 10000 Da) and densities on the in vitro and in vivo properties of liposomes. Results showed that, in the in vitro studies, PEGylated liposomes with different PEG MWs and densities maintained adequate physical or serum stability compared to liposomes without any surface modification. Meanwhile, liposomes with varying PEG molecular weights and densities exhibited excellent membrane stability and integrity and showed little cytotoxicity against HUVEC and RAW 264.7. PEGylated liposomes with varying MWs and densities of PEG did not significantly affect the release of the fluorescence dye DiD and exhibited good stability. On the other hand, both MWs and densities of PEG had a major influence on the pharmacokinetic properties of liposomes. The optimal enhancement of in vivo circulation time was observed at a PEG density of 10 % for liposomes modified with PEG₁₀₀₀, PEG_2000, and PEG₅₀₀₀, with group PEG₂₀₀₀ showing the highest AUC. For PEG with a molecular weight of 10000 Da, the elimination rate of PEGylated liposomes decreased as the density of PEG increased. These findings indicated that PEG MWs and densities both play critical roles in the formulation and physiochemical properties of nanomedicines, preliminarily providing guidance in selecting PEGs of suitable length and density in the designing of nanomedicines.