Controlled nucleation of lipid nanoparticles.

Autor: Nguyen J; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California 94143, USA., Walsh CL, Motion JP, Perttu EK, Szoka F
Jazyk: angličtina
Zdroj: Pharmaceutical research [Pharm Res] 2012 Aug; Vol. 29 (8), pp. 2236-48. Date of Electronic Publication: 2012 Apr 28.
DOI: 10.1007/s11095-012-0752-2
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz: