RANGE AND MAGNITUDE OF THE STERIC PRESSURE BETWEEN BILAYERS CONTAINING PHOSPHOLIPIDS WITH COVALENTLY ATTACHED POLY(ETHYLENE GLYCOL)

The interactive properties of liposomes containing phospholipids with covalently attached poly(ethylene glycol) (PEG-lipids) are of interest because such liposomes are being developed as drug delivery vehicles and also are ideal model systems for measuring the properties of surfa ce-grafted polymers. For bilayers containing PEG-lipids with PEG molec ular weights of 350, 750, 2000, and 5000, pressure-distance relations have been measured by X-ray diffraction analysis of liposomes subjecte d to known applied osmotic pressures. The distance between apposing bi layers decreased monotonically with increasing applied pressure for ea ch concentration of a given PEG-lipid. Although for bilayers containin g PEG-350 and PEG-750 the contribution of electrostatic repulsion to i nterbilayer interactions was significant, for bilayers containing PEG- 2000 and PEG-5000 the major repulsive pressure between bilayers was a steric pressure due to the attached PEG. The range and magnitude of th is steric pressure increased both with increasing PEG-lipid concentrat ion and PEG size, and the extension length of the PEG from the bilayer surface at maximum PEG-lipid concentration depended strongly on the s ize of the PEG, being less than 35 Angstrom for PEG-750, and about 65 Angstrom for PEG-2000 and 115 Angstrom for PEG-5000. The measured pres sure-distance relations have been modeled in terms of current theories (deGennes, 1987; Milner et al., 1988b) for the steric pressure produc ed by surface-grafted polymers, as modified by us to take into account the effects of polymer polydispersity and the possibility that, at lo w grafting densities, polymers from apposing bilayers surfaces can int erpenetrate or interdigitate. No one theoretical scheme is sufficient to account for all the experimental results. However, for a given pres sure regime, PEG-lipid size, and PEG-lipid surface density, the approp riately modified theoretical treatment gives a reasonable fit to the p ressure-distance data.