Lipids and Liposome Particles

Liposomes or lipid vesicles are self-assembled lipid structures in the shape of closed membrane capsules. The membrane is very similar to that of living cells and can encapsulate materials such as DNA, proteins, drugs, or other chemical substances. They can also be formed, manipulated, and modified in many ways. And because of its many excellent properties, it has been extensively studied in recent years.

"Microfluidics" can improve the production control of lipids/liposomes, especially in terms of small average size, narrow size distribution, and lamellar shape, which makes microfluidic approaches very attractive methods of lipid or liposome production for a wide range of industries.

Why Are Liposomes An Ideal Carrier?

A typical liposome contains a bilayer of long-chain lipid molecules, one end of which is polar. The polar heads of the molecules face the water phase, and the double-layer array of molecules allows the formation of pellets that are stable in the water phase and can also carry water payloads therein.

Figure.1 Structure of liposome. (Hwang J. Y, et al. 2016)

Its structure gives it many advantages, including:

• Engineering liposomes to mimic cell membranes can increase the chance of capsule fusion without any invasiveness.
• The modification of liposomes can successfully enhance the encapsulation, targeted delivery, and release capabilities.
• Since liposomes are composed of lipids and polar parts, they can carry therapeutic molecules with low hydrophilicity and lipophilicity at the same time.
• It is also advantageous that the surface of the liposome has the potential to be modified to configure its general properties such as stability, encapsulation efficiency, delivery accuracy, and release efficiency.
• For cancer therapy, liposomes have advantageous properties, such as enhanced EPR effect, which can effectively deliver small molecule therapy to tumors.
• The PEGylation of liposomes puts the nanocarrier in a "stealth" mode to avoid being swallowed by the phagocytes of the immune system in the body.

Lipids and Liposome Particles in Microfluidic Devices

Compared with conventional methods, microfluidic encapsulation has shown higher control over the physical properties of lipids or liposome particles. Microfluidic properties, such as low Reynolds number and diffusion-based mass transfer, make it the most feasible method for producing lipid-based nano-scale vesicle systems.

According to the microfluidic hydrodynamic focusing (MHF) technology developed by Jahn et al. in 2004, the lipid stream in the alcohol solution flows in the internal channel of the microfluidic chip and is intersected by the aqueous solution on both sides. When these three streams merge into one main microchannel, the alcohol diffuses into the aqueous solution. When the alcohol is diluted to a critical concentration, the lipids will spontaneously self-assemble into liposomes. The particle size of lipids or liposomes can be controlled by changing the flow rate ratio (FRR) of the two phases used.

Figure.2 Flow focusing vesicle production method, by Jahn et al. (a) Drawing of the vesicle forming a microfluidic channel. (b) A 3-D contour map of DiIC18 fluorescence intensity at the junction during vesicle formation. (Swaay D. V, et al. 2013)

Importantly, the flow focusing method can be used for high-throughput vesicle production. The reaction solution is prepared separately and can be loaded into the container on the microfluidic device, so that it can be operated continuously for a long time.

References

• Hwang J. Y, et al. (2016). "Small Molecule Therapeutic-loaded Liposomes as Therapeutic Carriers: from Development to Clinical Applications." RSC Adv. 6: 70592-70615.
• Swaay D. V et al. (2013). "Microfluidic Methods for Forming Liposomes." Lab Chip. 13: 752-767.

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