Characterization of the PEG layer of sterically stabilized liposomes: a SAXS study.

Synchrotron small-angle X-ray scattering analysis of the bilayer structure of a pharmacologically relevant sterically stabilized liposome system is presented. Describing the electron density profile of the bilayer with the superposition of Gaussian functions, the contribution of the poly(ethylene glycol) (PEG) layers to the total electron density was identified. The changes in the thickness of the PEG layer as well as the distribution of the PEG chains among the outer and inner leaflets of the bilayers were followed by changing the molar ratio of the PEG-lipid and the molar weight of the PEG molecule.

[1]  R. Neubert,et al.  Does sucrose influence the properties of DMPC vesicles? , 2003, Chemistry and physics of lipids.

[2]  A. Blaurock,et al.  Treatment of low angle x-ray data from planar and concentric multilayered structures. , 1966, Biophysical journal.

[3]  A. Brunger,et al.  X-ray scattering from unilamellar lipid vesicles , 2005 .

[4]  B. Mater.  Theory of the Grafted Polymer Brush , 1988 .

[5]  D. Lasič,et al.  Doxorubicin in sterically stabilized liposomes , 1996, Nature.

[6]  J. Bouwstra,et al.  Small angle X-ray scattering: possibilities and limitations in characterization of vesicles. , 1993, Chemistry and physics of lipids.

[7]  G. Pabst,et al.  Applications of neutron and X-ray scattering to the study of biologically relevant model membranes. , 2010, Chemistry and physics of lipids.

[8]  D. Klingenberg,et al.  Interactions between Polymer-Grafted Membranes in Concentrated Solutions of Free Polymer , 1996 .

[9]  S. Alexander,et al.  Adsorption of chain molecules with a polar head a scaling description , 1977 .

[10]  G. Kéri,et al.  A closer look at the structure of sterically stabilized liposomes: a small-angle X-ray scattering study. , 2010, The journal of physical chemistry. B.

[11]  R. Jahn,et al.  Structure parameters of synaptic vesicles quantified by small-angle x-ray scattering. , 2010, Biophysical journal.

[12]  Hiroshi Takahashi,et al.  Determination of asymmetric structure of ganglioside-DPPC mixed vesicle using SANS, SAXS, and DLS. , 2003, Biophysical journal.

[13]  D. Thompson,et al.  Size and structure of spontaneously forming liposomes in lipid/PEG-lipid mixtures. , 2002, Biophysical journal.

[14]  D. Needham,et al.  Range and magnitude of the steric pressure between bilayers containing phospholipids with covalently attached poly(ethylene glycol). , 1995, Biophysical journal.

[15]  Yechezkel Barenholz,et al.  Pharmacokinetics of Pegylated Liposomal Doxorubicin , 2003, Clinical pharmacokinetics.

[16]  K. Hristova,et al.  Effect of Bilayer Composition on the Phase Behavior of Liposomal Suspensions Containing Poly(ethylene glycol)-Lipids , 1995 .

[17]  Yechezkel Barenholz,et al.  Liposome application: problems and prospects , 2001 .

[18]  V. Gordeliy,et al.  Structural changes in dipalmitoylphosphatidylcholine bilayer promoted by Ca2+ ions: a small-angle neutron scattering study. , 2008, Chemistry and physics of lipids.

[19]  Y. Barenholz,et al.  Hydration of polyethylene glycol-grafted liposomes. , 1998, Biophysical journal.

[20]  P. Bösecke.  The high-flux beamline at the ESRF , 1992 .

[21]  D. Needham,et al.  Phase Behavior of a Lipid/Polymer-Lipid Mixture in Aqueous Medium , 1995 .

[22]  A. Bangham.  Surrogate cells or Trojan horses. The discovery of liposomes. , 1995, BioEssays : news and reviews in molecular, cellular and developmental biology.

[23]  Lawrence X. Yu,et al.  In vitro and in vivo characterizations of PEGylated liposomal doxorubicin. , 2011, Bioanalysis.

[24]  M. Martín-Pastor,et al.  Application of NMR spectroscopy to the characterization of PEG-stabilized lipid nanoparticles. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[25]  T. Narayanan,et al.  SAXS and USAXS on the high brilliance beamline at the ESRF , 2001 .

[26]  Scott T. Milner,et al.  Theory of the grafted polymer brush , 1988 .

[27]  C. Vermehren,et al.  An analytical model for the small‐angle scattering of polyethylene glycol‐modified liposomes , 2010 .

[28]  G. Pabst,et al.  Structural analysis of weakly ordered membrane stacks , 2003 .

[29]  P. G. de Gennes,et al.  Conformations of Polymers Attached to an Interface , 1980 .

[30]  D. Marsh,et al.  Lipid membranes with grafted polymers: physicochemical aspects. , 2003, Biochimica et biophysica acta.

[31]  Roi Asor,et al.  Following the structural changes during zinc-induced crystallization of charged membranes using time-resolved solution X-ray scattering , 2011 .

[32]  H. Junginger,et al.  Characterization of liposomes. The influence of extrusion of multilamellar vesicles through polycarbonate membranes on particle size, particle size distribution and number of bilayers , 1987 .

[33]  Y. Barenholz,et al.  Effect of grafted PEG on liposome size and on compressibility and packing of lipid bilayer. , 2005, Chemistry and physics of lipids.

[34]  Horst Halling,et al.  JUSIFA—A new user‐dedicated ASAXS beamline for materials science , 1989 .

[35]  S. Hirota,et al.  Effects of mixed polyethyleneglycol modification on fixed aqueous layer thickness and antitumor activity of doxorubicin containing liposome. , 2002, International journal of pharmaceutics.

[36]  T. McIntosh,et al.  Structure and phase behavior of lipid suspensions containing phospholipids with covalently attached poly(ethylene glycol). , 1995, Biophysical journal.