MODULATION OF INTERACTION FORCES BETWEEN BILAYERS EXPOSING SHORT-CHAINED ETHYLENE-OXIDE HEADGROUPS

The use of liposomes as drug delivery systems has been limited by thei r rapid clearance from circulation by the mononuclear phagocyte system . Recent studies have found that circulation times can be greatly enha nced by incorporating a small amount of modified lipids whose headgrou ps are derivatized with a bulky water soluble polymeric chain of poly ethylene oxide. We report here a systematic study using the Surface Fo rces Apparatus to measure directly the interactions between two phosph atidyl ethanolamine lipid bilayers, exposing this polymeric headgroup at different concentrations in the bilayer. We found that the force be comes repulsive at all separations and that the thickness of the steri c barrier could be controlled easily by adjusting the concentration of the modified lipids. Equilibrium force profiles were measured that we re reversible and largely insensitive to changes in electrolyte concen tration and temperature. The results have enabled the Dolan and Edward s theory for the steric forces of low coverage polymer surfaces and th e Alexander de Gennes theory for high coverage surfaces to be tested, and both were found to apply. We conclude that these simple theories c an be used to model the interactions of surprisingly short segments an d, hence, apply to such systems as lipids with bulky headgroups and li posomes containing a sterically stabilizing polymer.