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Precise control of liposome size using characteristic time depends on solvent type and membrane properties
Sunghak Choi1, Bongsu Kang1,2, Eunhye Yang3
1Center for Food and Bioconvergence, Department of Food Science and Biotechnology, Seoul National University, Seoul, 08826, South Korea.
Scientific Reports
|March 24, 2023
Summary
Controlling liposome size is key for drug delivery. Flow rates and solvents significantly impact liposome formation, with ethanol yielding smaller sizes than IPA, as confirmed by simulations.
Area of Science:
- Biotechnology
- Materials Science
- Chemical Engineering
Background:
- Liposome size is critical for drug delivery efficacy, affecting cellular uptake and biodistribution.
- Hydrodynamic focusing is used for nano-liposome synthesis, but flow dynamics' role in liposome formation remains unclear.
Purpose of the Study:
- To investigate how flow characteristics and solvent properties influence liposome size during microfluidic synthesis.
- To explore the impact of membrane composition, specifically cholesterol and short-chain lipids, on liposome size.
Main Methods:
- Liposomes of varying sizes (50-400 nm) were synthesized using different flow rate ratios in ethanol and isopropyl alcohol (IPA).
- Numerical simulations employing the characteristic time factor were used to predict liposome size and analyze microfluidic flow.
- Membrane rigidity was modulated by adding cholesterol and short-chain lipids, with changes confirmed by fluorescence anisotropy and polarity.
Main Results:
- Ethanol resulted in smaller, more homogeneous liposomes compared to IPA, attributed to lower viscosity and higher diffusivity.
- Numerical simulations successfully predicted liposome size based on flow characteristics.
- Increased membrane rigidity via cholesterol addition enlarged liposomes (40-530 nm), while short-chain lipids decreased size (130-230 nm) by destabilizing the bilayer.
Conclusions:
- Flow characteristics and solvent properties are crucial design parameters for controlling liposome size in microfluidic synthesis.
- Membrane composition significantly influences liposome size, offering a tunable parameter for drug delivery applications.
- This study provides a framework for optimizing microfluidic liposome production for targeted drug delivery.
