EFFECT OF BILAYER COMPOSITION ON THE PHASE-BEHAVIOR OF LIPOSOMAL SUSPENSIONS CONTAINING POLY(ETHYLENE GLYCOL)-LIPIDS

Liposomes containing phospholipids with covalently attached poly(ethyl ene glycol) (PEG-lipids) are being developed for use as carriers in in vivo drug delivery. A critical design parameter for these liposomes i s the maximum amount of PEG-lipids that can be incorporated into the p hospholipid bilayer before it is converted into a micelle. In this pap er, X-ray diffraction is used to determine this saturation limit of PE G-lipids for a variety of phospholipid bilayers with different tensile strengths and polymorphic properties. It is found that 15-20 mol % PE G-lipid can be incorporated into gel phase bilayers, liquid-crystallin e bilayers, and bilayers containing equimolar cholesterol. However, th e saturation limit of PEG-lipid in the bilayer is decreased to about 8 mol % when lysolipids are added to liquid-crystalline phase bilayers or when the gel phase bilayers are made with shorter hydrocarbon chain s. These data indicate that the phase transition from lamellar to mice llar phase for lipid suspensions containing PEG-lipids does not depend strongly on the tensile strength of the bilayer, but rather is determ ined primarily by the polymorphic properties of the Lipid molecules. T his study also measures the range and magnitude of the steric barrier provided by the incorporation of PEG-lipid into bilayers of different compositions. The steric barrier depends on the concentration of PEG-l ipid in the bilayer, with the incorporation of 10 mol % PEG-2000 into gel, liquid-crystalline, and cholesterol-containing bilayers providing a barrier that extends about 65 Angstrom from each bilayer surface.