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Pharm Res. 2012 Aug;29(8):2236-48. doi: 10.1007/s11095-012-0752-2. Epub 2012 Apr 28.

Controlled nucleation of lipid nanoparticles.

Author information

1
Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California 94143, USA.

Abstract

PURPOSE:

We describe a nucleation-based method which allows for the generation of monodisperse lipid nanoparticles over a range of diameters. Using a set of novel zwitterionic lipids and inverse phosphocholine lipids with pKas ranging from 2 to 5, we showed how the hydrodynamic diameter of lipid nanoparticles can be systematically manipulated over a 60 nm to 500 nm size range.

METHOD:

Lipid nanoparticles were prepared by adding an anti-solvent, such as water, to the organic phase containing the lipid components. This led to super-saturation and the spontaneous formation of particles.

RESULTS:

The growth and final particle size was controlled by the ratio of the components in the ternary system: lipid, organic solvent and aqueous phase. Particles with diameter below 125 nm were formed under conditions where the super-saturation coefficient was between 2.3 and 20. PEG-lipid served as an efficient growth inhibitor except at very high and low lipid concentrations. Encapsulation efficiency of siRNA into lipid nanoparticles was shown to be pH-dependent and requires the protonation of the anionic carboxylate groups of the zwitterionic lipids, emphasizing the importance of electrostatic forces.

CONCLUSION:

This process enables high encapsulation efficiency of nucleic acids and allows the size of lipid nanoparticles to be controlled.

PMID:
22544683
DOI:
10.1007/s11095-012-0752-2
[Indexed for MEDLINE]

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