ABSTRACT
HI. Theoretical Predictions for Terminally Grafted Polymer Chains .............................. 75 A. Alexander-de Gennes (A-dG) Polymer Brush Theory (1981) ............................ 75 B. Milner, Witten, and Cates (MWC) Mean Field Calculation for
Polymer Brushes (1988) ....................................................................................... 77 C. de Gennes Theory for Dilute Mushrooms (1985) ............................................... 78 D. Dolan and Edwards (D & E) Theory for Dilute Mushrooms (1974) .................. 78
IV. Results ......................................................................................................................... 79 A. Lateral Interactions of Lipid Monolayers at the Air-Water Interface ................. 79 B. Force Measurements of Lipid Bilayer Interactions ............................................. 80
V. Analysis of Results ...................................................................................................... 83 A. General Considerations ......................................................................................... 83 B. Comparison of Measured Force-Distance Profiles with Theory ......................... 84
1. Low Coverage (1.3%) ...................................................................................... 85 2. Moderate Coverage (4.5%) .............................................................................. 86 3. High Coverage (9.0%) ..................................................................................... 86
C. Comparison of Lateral Interactions with Scaling Theory ................................... 88
VI. Discussion and Conclusions ........................................................................................ 89
Acknowledgments ................................................................................................................. 90
References ............................................................................................................................. 90
The presence of terminally grafted polymers at the solid-solution interface of colloidal particles, liposomes, biological cells, and other biosurfaces is currently receiving considerable attention, especially regarding sterically stabilized liposomes used for drug delivery. Previously, the use of liposomes as drug delivery vesicles was limited by their rapid clearance from
circulation by the mononuclear phagocytotic system. Recent studies have found that circulation times can be greatly enhanced, from hours to days, by incorporating into the liposomes a small amount of modified lipids whose headgroups are derivatized with polyethylene oxide (PEO) creating what are now referred to as "Stealth"® liposomes. 1-5 The enhanced circulation time is believed to be due to steric stabilization of the liposomes by the grafted polymer, preventing their close approach to cellular surfaces in the body, which is necessary to prevent recognition interactions, adhesion binding, and subsequent destruction of the liposomes by the immune system. The special properties of PEO: chemical inertness, biocompatibility, water solubility (hydrophilicity), insensitivity to changes in solution ionic conditions due to its nonionic character, and low protein adsorption have made it a particularly suitable polymer for use as a steric stabilizer in aqueous media, including body fluids. 6-9
Although the exact nature of the stealth property of such liposomes in vivo is still not fully understood due to the complexities of living organisms, model systems have been studied. 10 Using X-ray diffraction, Needham and colleagues (1992) recently reported that at moderate surface coverages the polymer moiety acts as a steric barrier, increasing the repulsion between oriented multilayers and unoriented multi walled liposomes. 11 ·12 We have extended this work and present here the results of detailed measurements of the interaction forces, F, as a function of distance, D, between supported lipid bilayers of double-chained zwitterionic lipids in aqueous solution as modified by the attachment ofPEO chains to the headgroups. 13 In addition, the lateral interactions (pressure-area or Il-A curves) of headgroup-attached PEO chains in mono layers at the air-water interface were also measured. The results of the force-distance (F-D) measurements and corresponding Il-A curves were compared with each other and with various theories which attempt to model the steric interactions of grafted polymer chains.
