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Cholesteryl hemisuccinate exhibits pH sensitive polymorphic phase behavior.

I M Hafez1, P R Cullis

  • 1Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of British Columbia, 2146 Health Sciences Mall, Vancouver, B.C., Canada. ismail@interchange.ubc.ca

Biochimica Et Biophysica Acta
|January 13, 2000
PubMed
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Cholesteryl hemisuccinate (CHEMS) exhibits pH-sensitive polymorphism, undergoing fusion below pH 4.3. This pH-dependent behavior of CHEMS is key to the sensitivity of mixed CHEMS and DOPE vesicles.

Area of Science:

  • Lipid bilayer self-assembly
  • Membrane biophysics
  • Drug delivery systems

Background:

  • Cholesteryl hemisuccinate (CHEMS) is an acidic cholesterol ester.
  • CHEMS forms bilayers in neutral and alkaline aqueous media.
  • CHEMS is used with dioleoylphosphatidylethanolamine (DOPE) for pH-sensitive fusogenic vesicles.

Purpose of the Study:

  • To investigate the pH-sensitive polymorphism of CHEMS itself.
  • To understand the contribution of CHEMS to the pH sensitivity of CHEMS/DOPE vesicles.

Main Methods:

  • Large unilamellar vesicles (LUV) composed of CHEMS were prepared.
  • Lipid mixing assays were used to monitor vesicle fusion.
  • Freeze-fracture electron microscopy visualized lipid phases.

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Main Results:

  • CHEMS LUV demonstrated pH-sensitive fusogenic properties.
  • Below pH 4.3, CHEMS LUV underwent fusion.
  • Freeze-fracture electron microscopy revealed H( parallel) phase lipid structures below pH 4.3.

Conclusions:

  • CHEMS exhibits intrinsic pH-sensitive polymorphism.
  • The pH-dependent phase behavior of CHEMS influences the sensitivity of CHEMS/DOPE vesicles.