| Autor: |
Nguyen, Juliane, Walsh, Colin, Motion, J., Perttu, Emily, Szoka, Francis |
| Předmět: |
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| Zdroj: |
Pharmaceutical Research; Aug2012, Vol. 29 Issue 8, p2236-2248, 13p, 1 Black and White Photograph, 2 Diagrams, 1 Chart, 7 Graphs |
| 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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