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Formulating and Characterizing Lipid Nanoparticles for Gene Delivery using a Microfluidic Mixing Platform
Published on: February 25, 2021
Controlled nucleation of lipid nanoparticles
Juliane Nguyen1, Colin L Walsh, J P Michael Motion
1Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California 94143, USA.
Pharmaceutical Research
|May 1, 2012
Summary
A novel nucleation method allows precise control over lipid nanoparticle size (60-500 nm) using specific lipids and controlled supersaturation. This technique enhances nucleic acid encapsulation efficiency.
Area of Science:
- Nanotechnology
- Materials Science
- Biochemistry
Background:
- Lipid nanoparticles (LNPs) are crucial for drug and nucleic acid delivery.
- Controlling LNP size and encapsulation efficiency remains a key challenge in formulation development.
Purpose of the Study:
- To develop a nucleation-based method for generating monodisperse lipid nanoparticles.
- To demonstrate systematic control over LNP hydrodynamic diameter from 60 nm to 500 nm.
- To investigate factors influencing LNP size and encapsulation efficiency.
Main Methods:
- Utilized novel zwitterionic and inverse phosphocholine lipids with tunable pKas.
- Prepared LNPs via anti-solvent addition to an organic lipid phase, inducing supersaturation.
- Controlled particle size by adjusting the ratio of lipid, organic solvent, and aqueous phase.
Main Results:
- Achieved monodisperse LNPs with diameters ranging from 60 nm to 500 nm.
- Identified supersaturation coefficients (2.3-20) for particle formation below 125 nm.
- Demonstrated pH-dependent siRNA encapsulation, highlighting the role of electrostatic interactions and zwitterionic lipid protonation.
Conclusions:
- The nucleation method enables tunable LNP size control.
- High encapsulation efficiency of nucleic acids is achievable with this process.
- Understanding lipid properties and formulation conditions is key for optimized LNP generation.
