title: Interaction of polyethyleneglycol-phospholipid conjugates with cholesterol-phosphatidylcholine mixtures: sterically stabilized liposome formulations.
abstract: OBJECTIVE
  The purpose of this study was to investigate polyethyleneglycol (PEG)-phosphatidylethanolamine (PE) conjugate interaction with cholesterol-phospholipid mixtures in an attempt to explain the effect of cholesterol on liposome circulation time.
  
  
  METHODS
  Differential scanning calorimetry, NMR, electron microscopy, dynamic light scattering and fluorescence spectroscopy were the major methods used.
  
  
  RESULTS
  Studies performed in the absence of cholesterol indicated the formation of three distinct physical states depending on the chain length of PEG in PEG-PE. Mixed micelle formation was observed at concentrations of PEG(1,000)-DPPE above 7 mol-% of lipid. Phase separated lamellae were observed at all concentrations of PEG( 12,000)-DPPE (Bedu-Addo et al. Pharm. Res. 13:710-717 (1996)). Upon incorporation of high concentrations of cholesterol >30 mol% into the lipid bilayer, the formation of phase separated lamellae was completely inhibited and the formation of mixed micelles significantly reduced. At high concentrations of PEG(1,000)-PE, solubilization of the bilayer occurred with preferential solubilization of cholesterol over phosphatidylcholine. Maximum steric stabilization (surface protection) was observed with low concentrations of short chain PEG-PE and high concentrations of cholesterol.
  
  
  CONCLUSIONS
  The study provides a physical mechanism for the following observations: the blood circulation time is significantly increased or decreased with liposomes highly enriched with cholesterol or PEG-PE respectively.
authors.affiliation: The Liposome Company, Princeton, New Jersey 08540, USA.
authors.forename: F K
authors.initials: FK
authors.lastname: Bedu-Addo
authors.forename: P
authors.initials: P
authors.lastname: Tang
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.forename: L
authors.initials: L
authors.lastname: Huang
mesh_terms: D002152:Calorimetry, Differential Scanning; D002784:Cholesterol / Q000737:chemistry*; D004337:Drug Carriers; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy; D008567:Membranes, Artificial; D008854:Microscopy, Electron; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013050:Spectrometry, Fluorescence
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D008567:Membranes, Artificial; D010743:Phospholipids; D011092:Polyethylene Glycols; D002784:Cholesterol