Effect of Bilayer Composition on the Phase Behavior of Liposomal Suspensions Containing Polyethylene glycol)–Lipids

Kalina Hristova, Anne Kenworthy, Thomas J. McIntosh

Research output: Contribution to journalArticlepeer-review

95 Scopus citations


Liposomes containing phospholipids with covalently attached poly(ethylene glycol) (PEG-lipids) are being developed for use as carriers in in vivo drug delivery. A critical design parameter for these liposomes is the maximum amount of PEG-lipids that can be incorporated into the phospholipid bilayer before it is converted into a micelle. In this paper, X-ray diffraction is used to determine this saturation limit of PEG-lipids for a variety of phospholipid bilayers with different tensile strengths and polymorphic properties. It is found that 15–20 mol % PEG-lipid can be incorporated into gel phase bilayers, liquid-crystalline bilayers, and bilayers containing equimolar cholesterol. However, the 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 chains. These data indicate that the phase transition from lamellar to micellar phase for lipid suspensions containing PEG-lipids does not depend strongly on the tensile strength of the bilayer, but rather is determined primarily by the polymorphic properties of the lipid molecules. This 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-lipid 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 A from each bilayer surface.

Original languageEnglish (US)
Pages (from-to)7693-7699
Number of pages7
Issue number23
StatePublished - Nov 1 1995
Externally publishedYes

ASJC Scopus subject areas

  • Organic Chemistry
  • Polymers and Plastics
  • Inorganic Chemistry
  • Materials Chemistry


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