Steric Stabilization of Lipid/Polymer Particle Assemblies by Poly(ethylene glycol)-Lipids

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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 degrees 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.

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