Liposome nanoparticles synthesis

Despite considerable progress in recent years, various disease’ diagnosis and treatments continue to present constraints, such as low sensitivity or specificity, drug toxicity, and severe side effects1. Cancer represents one of the best examples of a disease where localized delivery of therapeutics is of high importance, as the potent yet toxic mechanisms of action of such compounds can lead to an effective response or side effects. Today, most drug formulations are not capable of targeting specific sites of interest. Nanoparticle-based drug delivery platforms have emerged as suitable vehicles for overcoming these limitations2. Nanoparticles, such as liposomes, have proven advantageous at preserving therapeutic material and allowing for extended half-lives of drugs within the body3. In this application note the Raydrop developed and manufactured by Secoya is used to perform the synthesis.


Liposomes were discovered in the 1960s. These hollow nanoparticles are phospholipid vesicles consisting of at least one lipid bilayer (figure 1). This bilayer is usually composed of amphiphilic phospholipids that have a hydrophilic phosphate head and a hydrophobic tail consisting of two fatty acid chains. This structural feature has facilitated liposomes’ applications, including their use as artificial cell membranes, carriers for drug delivery systems, encapsulating agents for food ingredients, and analytical tools4–8.

During the COVID-19 pandemic, the first vaccines to reach clinical trials were based on viral vector and nucleic acid technologies. One of the most promising vaccine candidates was based on nucleoside-modified mRNA and encapsulated within lipid nanoparticles (LNP)9. This only confirms the need for lipidic nanoparticles for present and future drug delivery applications.

liposome scheme
Figure 1: A liposome is a spherical vesicle having at least one lipid bilayer. The liposome can be used as a drug delivery vehicle for the administration of nutrients and pharmaceutical drugs, such as lipid nanoparticles in mRNA vaccines, and DNA vaccines.

Comparison with another production method

Batch methodFluigent microfluidic method
Particle size distributionLowHigh
Live particle size controlNoPrecise
Range of particle sizeLimited size rangeWide size range
Continuous (/in line) productionNoYes

Materials and methods

liposome production scheme setup
Figure 2: Scheme of the fluidic setup
Figure 2: Pictures of the Fluigent equipment

Partial results

A liquid stream of ethanol with lipid, surrounded by PBS
A liquid stream of ethanol with lipid, surrounded by PBS

Liposome mean diameter and polydispersity index (PDI)
Liposome mean diameter and polydispersity index (PDI) as a function of the flow rate ration (FRR)


Liposome nanoparticles prove advantageous at solubilizing therapeutic substances. Macroscale batch methods widely employed for liposome production lack control on liposome morphology, size, and distribution. Microfluidic systems allow for the production of highly monodisperse liposome nanoparticles. We have demonstrated the production of liposomes using a microfluidic system consisting of pressure-based flow controllers and the Raydrop™ microfluidic device with standard configuration. Liposomes ranging from 30 to 150 nm were generated. Sizes can be adjusted by controlling the device flow input parameters, particularly the flow rate ratio (FRR). The polydispersity index (PDI) ranges from 0,07 to 0,15. This system enables the synthesis of liposomes for drug delivery applications, as encapsulating agents for food ingredients, or for other applications requiring nano-sized and spherical liposomes.

A complete, cost-effective, and commercially-available platform for the on-demand production of monodisperse liposome nanoparticles is now available. This allows for control of liposome size and frequency by adjusting flow parameters.


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