Liposomes are very well known, and their popularity is increasing with new applications and technologies emerging steadily. Microfluidic technology enables the increased production control over the liposome’s physical properties, especially in terms of small mean size, narrow size distribution and lamellarity. These characteristics make microfluidic approaches very attractive methods of liposome production for a wide range of industries.

 

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Why are liposomes ideal carriers?

Liposomes are vesicular, biocompatible nano-particles formed by one or more lipid bi-layer membranes that surround an aqueous core. Scientists recognize their numerous advantages, which include:

  • Increased efficacy of therapeutic drugs
  • Non-toxic & non-immunogenic properties
  • Biocompatible & fully biodegradable
  • Increased stability for encapsulations
  • Delivery of both hydrophilic and hydrophobic drugs

The lipid bilayer is comprised of amphiphilic molecules (phospholipids). These molecules generally consist of two hydrophobic fatty acid “tails” and a hydrophilic phosphate “head”.

The amphiphilic structure of liposome particles enables the encapsulation of both hydrophilic and hydrophobic pharmaceutical drugs and nutrients. Phospholipids form an insoluble “bubble”, protecting the active pharmaceutical ingredient (API) from the harsh environment of the digestive system, allowing for absorption through the gut wall. From here, particles gravitate through the bloodstream toward the site of cell damage, and the phospholipids are stripped away to be used by the body to build new cells. At this point the API, which has remained untouched during transit, is released to treat the affected area. This makes liposomes a very attractive biological system, widely employed as a drug delivery vehicle.

Structure of a liposome

Does size really matter?

In a single word, yes! Liposome size can impact how and when the contents of the liposome are released. Size also impacts the apbsorption and transport properties of the liposome throughout the body.

 

How does microfluidic technology help?

Microfluidics provides a tool to manipulate liquids, gases, droplets, cell and particles within micro-channel geometries. The generation of droplets involves controlling the jetting to dripping transition when liquid droplets are pushed into a carrier fluid via a specific chip geometry. The droplets are stabilized using surfactants to avoid coagulation and separation.

Among its various advantages, microfluidic technology has the ability to create three-dimensional flow patterns that achieve precise control over immiscible and miscible fluid mixing. 

Microfluidic synthesis

Microfluidic encapsulation methods have demonstrated potential for achieving higher control over the physical properties of the final liposome product than conventional batch methods. Typical microfluidics characteristics, such as low Reynolds number and diffusion dominated mass transfer, make it the most viable method for producing lipid-based nanoscale vesicular systems with the potential for clinical application.

Liposome Synthesis - Microfluidic Applications

Microfluidic Hydrodynamic Focusing

The Microfluidic Hydrodynamic Focusing (MHF) technique, developed by Jahn et al. in 2004, utilises these typical characteristics of microfluidics to produce highly controlled liposomes. This method relies on the use of microfluidic devices with a cross flow geometry. Typically, a stream of lipid in alcohol solution is forced to flow in the inner channel of the device. The lipid stream is intersected and sheathed by two lateral (or coaxial) streams of a aqueous phase (distilled water or aqueous buffers). In this way, the lipid-containing stream is hydrodynamically focused into a narrow sheet. During this process the diffusion of alcohol into the aqueous phase and vice-versa triggers the formation of liposomes by a mechanism described as “self-assembly”. Liposome particle size can be controlled by changing the flow rate ratio (FRR) of the two phases used.

System solutions

Dolomite’s Liposome Synthesis Systems are an exceptional solution for this application as they use microfluidic mixing methods to generate monodisperse particles and emulsions, offering precise product characteristics, high levels of reproducibility, and effortless scale-up.

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Further reading

Continuous microfluidic synthesis of liposome nanoparticles by hydrodynamic flow focusing

Methodology for generation of monodisperse liposome nanoparticles in sizes ranging from 30 nm to 90 nm using precipitation method.

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