PURPOSE: 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.
PURPOSE: 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: V P Torchilin; V G Omelyanenko; M I Papisov; A A Bogdanov; V S Trubetskoy; J N Herron; C A Gentry Journal: Biochim Biophys Acta Date: 1994-10-12
Authors: Elizabeth Hood; Eric Simone; Paritosh Wattamwar; Thomas Dziubla; Vladimir Muzykantov Journal: Nanomedicine (Lond) Date: 2011-09 Impact factor: 5.307
Authors: Mathias Viard; Henry Reichard; Bruce A Shapiro; Farukh A Durrani; Aimee J Marko; R Michelle Watson; Ravindra K Pandey; Anu Puri Journal: Nanomedicine Date: 2018-07-27 Impact factor: 5.307
Authors: Wynter J Duncanson; Kelleny Oum; John R Eisenbrey; Robin O Cleveland; Margaret A Wheatley; Joyce Y Wong Journal: Biotechnol Bioeng Date: 2010-06-15 Impact factor: 4.530