Spontaneous liposome formation induced by grafted poly(ethylene oxide) layers: Theoretical prediction and experimental verification

Igal Szleifer*, Oleg V. Gerasimov, David H. Thompson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


Spontaneous liposome formation is predicted in binary mixtures of fluid phase phospholipids and poly(n)ethylene oxide (PEO)-bearing lipids by 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 were tested by using cast films of 1,2-diacyl-sn-glycerophosphocholines (e.g., egg L-α-lecithin, 1,2- dimyristoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3- phosphocholine, and 1,2-distearoyl-sn-glycero-3-phosphocholine) and 1,2- dipalmitoyl-sn-glycerophosphatidylethanolamine-PEO conjugates (i.e., 1,2- dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxypoly(ethylene glycol)2000]carboxamide and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine- N-[methoxypoly(ethylene oxide)5000] carboxamide) that were hydrated above their gel-liquid crystal phase transition temperatures. Particle sizes of the resulting dispersions, analyzed by quasielastic light scattering, solute retention, 31P NMR, and freeze-fracture electron microscopy measurements, confirmed the single chain mean field predictions. These data indicate that thermodynamically stable, unilamellar liposomes are formed spontaneously by simple hydration of fluid phase phospholipid bilayer films containing low molar ratios of PEO-based amphiphiles. They further suggest that the equilibrium size and colloidal properties of fluid phase, PEO-modified liposomes can be predicted by using this theoretical approach. The implication of these results on the design and processing of sterically stabilized liposomes used in drug delivery applications also is described.

Original languageEnglish (US)
Pages (from-to)1032-1037
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number3
StatePublished - Feb 3 1998

ASJC Scopus subject areas

  • General


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