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Updated: Apr 30, 2026
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Formulating and Characterizing Lipid Nanoparticles for Gene Delivery using a Microfluidic Mixing Platform
Published on: February 25, 2021
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Generation of geometrically ordered lipid-based liquid-crystalline nanoparticles using biologically relevant
Wye Khay Fong1, Stefan Salentinig, Clive A Prestidge
1Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University , 381 Royal Parade, Parkville, Victoria 3052, Australia.
Summary
Researchers developed a novel method to create lipid nanoparticles with internal cubic structures (cubosomes) using enzymatic reactions. This approach offers a new way to generate advanced nanostructured materials, avoiding common preparation challenges.
Area of Science:
- Nanotechnology
- Materials Science
- Biochemistry
Background:
- Lipid nanoparticles, particularly those with internal bicontinuous cubic phases (cubosomes), are valuable nanostructured materials.
- Traditional methods for cubosome synthesis can be complex and face challenges.
Purpose of the Study:
- To develop a novel, enzyme-mediated method for synthesizing high-symmetry lipid nanoparticles with internal cubosome structures.
- To investigate the kinetics and structural transformations during the formation process.
Main Methods:
- Preparation of emulsions containing phytantriol (nondigestible lipid) and short-chained triglycerides.
- Enzymatic lipolysis of the triglyceride to induce phase separation and crystallization.
- Time-resolved small-angle X-ray scattering (SAXS) to monitor structural changes.
- Cryo-transmission electron microscopy (cryo-TEM) for structural visualization.
Main Results:
- Successful formation of lipid nanoparticles with internal cubic phase structures (cubosomes).
- Enzymatic lipolysis triggered the disorder-to-order transition, leading to cubosome crystallization.
- SAXS data revealed the kinetics of the structural transition.
- Cryo-TEM confirmed the cubosome structure and showed an absence of liposomes.
Conclusions:
- A new "sideways" method for generating lipid-based nanostructured materials has been established.
- This enzymatic approach offers an alternative to conventional top-down and bottom-up synthesis methods.
- The method provides precise control over the formation of cubosomes with internal cubic phases.
