PEG-grafted phospholipids in vesicles: Effect of PEG chain length and concentration on mechanical properties

Incorporation of low molecular weight poly-ethylene glycol (PEG) - grafted phospholipids in vesicle bilayers is known to increase the circulation time of liposomal drug delivery vehicles. Mechanical properties of giant unilamellar DPPC vesicles containing varying concentrations of DSPE-PEG (PEG MW: 550, 1000 and 2000) were measured by micropipette aspiration assay or osmotic swelling. While the area compressibility modulus did not change significantly, the bending modulus and water permeability of the bilayer was found to increase with increasing mole fraction of DSPE-PEG. This increase was more pronounced for higher molecular weight PEG. The measured bending modulus agreed with that predicted by scaling theory only at low mole fractions of DSPE-PEG. The water permeability was also measured as a function of the increase in area per lipid (due to steric repulsion between PEG chains), and for the same area per lipid, the PEG chain with MW 550 provided a greater resistance to water transport across the vesicle membrane compared to PEG 1000 and 2000. Lysis tension of the membrane, determined by osmotic lysis method at different loading rates showed a decrease in membrane strength on inclusion of the polymer lipid. These results suggest that liposome lifetime in the circulation and the rate of drug delivery are affected by the molecular weight and concentration of PEG in the bilayer.