Chemistry and Physics of Lipids 135 (2005) 117–129 Effect of grafted PEG on liposome size and on compressibility and packing of lipid bilayer Olga Garbuzenko, Yechezkel Barenholz ∗ , Aba Priev Laboratory of Membrane and Liposome Research, Hebrew University–Hadassah Medical School, Jerusalem 91120, Israel Received 16 November 2004; received in revised form 8 February 2005; accepted 8 February 2005 Available online 19 March 2005 Abstract The aim of this study was to elucidate the effect of various mole percentages (0–25 mol%) of 2000 Da polyethylene glycol–disteroylphosphoethanolamine (PEG–DSPE) in the presence or absence of 40 mol% cholesterol and the effect of degree of saturation of phosphatidylcholine (PC) on the size and the lipid bilayer packing of large unilamellar vesicles (LUV). Egg PC (EPC, unsaturated) LUV and fully hydrogenated soy PC (HSPC, saturated) LUV partial specific volume, specific com- pressibility, size, and packing parameter (PP) of lipids were characterized by measurements of density, ultrasonic velocity, specific turbidity, and dynamic light scattering. Liposome size and specific turbidity decreased with increase in temperature and PEG–DSPE mol%, except at 7 ± 2 mol%. At this PEG–DSPE mol%, an anomalous peak in liposome size of 15 ± 5 nm was observed. We attribute this effect mainly to the change in the spatial structure of the PEG–DSPE molecule, depending on whether the grafted PEG is in the mushroom or brush configuration. In the mushroom regime, i.e., when the grafted PEG is up to 4 mol% in LUV, the PEG moiety did not affect the additive PP of the lipids in the bilayer, and the PP value of PEG–DSPE is 1.044; while in the brush regime, i.e., when the grafted PEG is higher than 4mol%, the PP of PEG–DSPE decreases exponentially, reaching the value of 0.487 at 30mol% of grafted lipopolymer. The specific compressibility and additive PP values for the mixture of matrix lipid (EPC or HSPC), cholesterol, and PEG–DSPE for all liposome compositions investigated reached their maximum at 7 ± 2 mol% PEG–DSPE, the concentration of PEG–DSPE at which the highest biological stability of the LUV is achieved. © 2005 Published by Elsevier Ireland Ltd. Keywords: PEG–DSPE packing parameter; Liposome size; Bulk compressibility Abbreviations: Chol, cholesterol; DLS, dynamic light scattering; DSPE, distearoylphosphoethanolamine; HSPC, hydrogenated soy phos- phatidylcholine; EPC, egg phosphatidylcholine; LD, liquid disordered; LO, liquid ordered; LUV, large unilamellar vesicles; MLV, multilamellar vesicles; PC, phosphatidylcholine; PEG, polyethylene glycol; PP, packing parameter; SO, solid ordered; T m , phase transition temperature ∗ Corresponding author. Tel.: +972 2 6758507; fax: +972 2 6757499. E-mail address: yb@cc.huji.ac.il (Y. Barenholz). 0009-3084/$ – see front matter © 2005 Published by Elsevier Ireland Ltd. doi:10.1016/j.chemphyslip.2005.02.003