title: Repulsive interactions and mechanical stability of polymer-grafted lipid membranes.
abstract: Liposome membranes containing lipids with covalently attached poly(ethylene glycol) (PEG-lipid) are currently being developed as drug delivery systems. These, so called, 'Stealth' liposomes have a relatively long half life (approximately 1 day) in blood circulation and show an altered biodistribution in vivo. The extended lifetime appears to result from a steric stabilization of the liposome by the grafted polymer. In order to characterize the surface structures that promote steric stability in such polymer-grafted lipid bilayer systems, we have used X-ray diffraction to measure the structural organization and interbilayer repulsion for lipid/cholesterol (2:1) bilayers incorporating 4 mol% of a PEG-lipid in which the molecular weight of the PEG moiety was 1900 g/mol. At this concentration, applied pressure versus interbilayer distance relations showed that the grafted polymer moiety extended approximately 50 A from the lipid surface and gave rise to a strong, slowly decaying repulsive pressure between membranes that opposed their close approach. Also, the pressure vs. distance relations were only modestly altered by changing the ionic strength of the medium (1 mM NaCl and 100 mM NaCl). Therefore, even though the PEG-lipid headgroup bears a negative charge, the long range pressure cannot be due primarily to an electrostatic double layer pressure. Measurements of lipid bilayer elasticity using micropipet manipulation showed that PEG-lipid did not change the cohesive properties of lipid/cholesterol liposomes which was consistent with the X-ray structural data showing that the PEG-lipid did not change the normal structure of the bilayer interior. From these data we conclude that the repulsive barrier properties of lipid-grafted PEG polymer chains originate mainly from a steric pressure and that this simple polymer steric stabilization is the basis for the extended in vivo circulation times observed for polymer-grafted liposomes.
authors.affiliation: Mechanical Engineering and Materials Science, Duke University, Durham, NC 27706.
authors.forename: D
authors.initials: D
authors.lastname: Needham
authors.forename: T J
authors.initials: TJ
authors.lastname: McIntosh
authors.forename: D D
authors.initials: DD
authors.lastname: Lasic
mesh_terms: D004553:Electric Conductivity; D008051:Lipid Bilayers / Q000097:blood / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011312:Pressure; D013499:Surface Properties; D014961:X-Ray Diffraction
chemical_list: D008051:Lipid Bilayers; D011092:Polyethylene Glycols