Web Release Date: October 25,
Steric Stabilization of Lipid/Polymer Particle Assemblies by Poly(ethylene glycol)-Lipids
and
UMR 2714/CNRS/bioMérieux, Systèmes Macromoléculaires et Physiopathologie Humaine, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France, Laboratoire des Matériaux Inorganiques, UMR 6002, Université Blaise Pascal, 24 Avenue des Landais, 63177 Aubière Cedex, France, and Laboratoire des Matériaux Polymères et Biomatériaux, UMR 5223 IMP, Université Lyon 1, Bât. ISTIL, 15 Bd Latarjet, 69621 Villeurbanne Cedex, France
Received July 9, 2007
Revised August 22, 2007
Abstract:
Biocompatible and biodegradable assemblies consisting of spherical particles coated with lipid layers were prepared
from sub-micrometer poly(lactic acid) particles and lipid mixtures composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-3-trimethylammonium-propane. These original colloidal assemblies, named
LipoParticles, are of a great interest in biotechnology and biomedicine. Nevertheless, a major limitation of their
use is their poor colloidal stability toward ionic strength. Indeed, electrostatic repulsions failed to stabilize
LipoParticles in aqueous solutions containing more than 10 mM NaCl. By analogy with the extensive use of
poly(ethylene glycol) (PEG)-lipid conjugates to improve the circulation lifetime of liposomes in vivo, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] with various PEG chain lengths
was added to the lipid formulation. Here, we show that LipoParticle stabilization was enhanced at least up to 150
mM NaCl (for more than 1 year at 4 
C). To determine the structure of PEG-modified LipoParticles as a function
of the PEG chain length and the PEG-lipid fraction in the lipid formulation, a thorough physicochemical
characterization was carried out by means of many techniques including quasi-elastic light scattering, zeta potential
measurements, transmission electron microscopy, 1H NMR spectroscopy, and small-angle X-ray scattering. Finally,
an attempt was made to link the resulting structural data to the colloidal behavior of PEG-modified LipoParticles.
Download the full text: PDF | HTML
