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Microfluidic Flow-Focusing for Size-Controlled Formation of Cubosomes
Celso J O Ferreira1,2,3,4, Margarida Barros1,2, Marco Fornasier4
1INL-International Iberian Nanotechnology Laboratory, Braga 4715-330, Portugal.
Langmuir : the ACS Journal of Surfaces and Colloids
|October 17, 2025
Summary
A new microfluidic method precisely controls cubosome size for drug delivery by adjusting flow rates during solvent exchange. This technique offers tunable particle sizes, outperforming traditional bulk methods.
Area of Science:
- Materials Science
- Nanotechnology
- Pharmaceutical Sciences
Background:
- Cubosomes are advanced lipid-based nanosystems for drug delivery.
- Controlling cubosome size is crucial for optimizing drug delivery efficacy.
- Traditional bulk solvent exchange methods lack precise size control.
Purpose of the Study:
- To develop a microfluidic hydrodynamic flow-focusing approach for cubosome preparation.
- To enable tunable control over cubosome particle size via solvent exchange.
- To investigate the influence of flow rate ratio on cubosome self-assembly kinetics and size.
Main Methods:
- Utilized a cross-shaped microfluidic device for hydrodynamic flow-focusing.
- Prepared precursor solutions of phytantriol lipid in ethanol.
- Focused precursor solution with lateral streams of water containing Pluronic F127 stabilizer for controlled solvent exchange and self-assembly.
Main Results:
- Successfully tuned cubosome sizes from 195 nm down to 125 nm.
- Demonstrated a monotonic decrease in particle size with increasing flow rate ratio (QR).
- Achieved low-to-moderate polydispersity indices, with statistically significant trends (p ≤ 0.011).
Conclusions:
- Microfluidic hydrodynamic flow-focusing offers precise control over cubosome size.
- This method provides a significant advantage over bulk solvent exchange for tunable nanoparticle preparation.
- Further apparatus optimization can enhance reproducibility and scalability for advanced drug delivery applications.
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