SPONTANEOUS LIPOSOME FORMATION INDUCED BY GRAFTED POLY(ETHYLENE OXIDE) LAYERS - THEORETICAL PREDICTION AND EXPERIMENTAL-VERIFICATION

Spontaneous liposome formation is predicted in binary mixtures of flui d phase phospholipids and poly(n)ethylene oxide (PEO)-bearing lipids b y using single chain mean field theory. The range of stability of the spontaneous liposomes is determined as a function of percentage of PEO -conjugated lipids and polymer molecular weight, These predictions wer e tested by using cast films of 1,2-diacyl-sn-glycerophosphocholines ( e.g., egg L-alpha-lecithin, 1,2-dimyristoyl-sn-glycero-3-phosphocholin e, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, and 1,2-distearoyl-sn- glycero-3-phosphocholine) and dipalmitoyl-sn-glycerophosphatidylethano lamine-PEO conjugates (i.e., -glycero-3-phosphoethanolamine-N-[methgly col)2000] carboxamide and cero-3-phosphoethanolamine-N-[methoxypoly(et hylene oxide)5000] carboxamide that were hydrated above their gel-liqu id crystal phase transition temperatures. Particle sizes of the result ing dispersions, analyzed by quasielastic light scattering, solute ret ention, P-31 NMR, and freeze-fracture electron microscopy measurements , confirmed the single chain mean field predictions, These data indica te that thermodynamically stable, unilamellar liposomes are formed spo ntaneously by simple hydration of fluid phase phospholipid bilayer fil ms containing low molar ratios of PEG-based amphiphiles. They further suggest that the equilibrium size and colloidal properties of fluid ph ase, PEG-modified liposomes can be predicted by using this theoretical approach, The implication of these results on the design and processi ng of sterically stabilized liposomes used in drug delivery applicatio ns also is described.