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 effects[1]. 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 limitations[2]. Nanoparticles, such as liposomes, have proven advantageous at preserving therapeutic material and allowing for extended half-lives of drugs within the body[3].

Liposomes nanoparticles are specialized delivery vehicles that serve multiple roles in enhancing the capabilities of active pharmaceutical ingredients (APIs). They can shield a drug from detection by the body’s immune system, and they serve to help solubilize highly lipophilic drug molecules or modulate the pharmacokinetics and biodistribution of the API.

 In this application note the Raydrop developed and manufactured by Secoya is used to perform the synthesis.

Secoya developed and manufactured the RayDrop used to perform this application note.



Liposome nanoparticles 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 liposome applications, including their use as artificial cell membranes, carriers for drug delivery systems, encapsulating agents for food ingredients, and analytical tools [4–8].

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 confirms the need for lipidic nanoparticles for present and future drug delivery applications.

LIPOSOME nanoparticles 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.

In recent years, liposomes nanoparticles have attracted significant attention as a trusted class of drug delivery vehicles. Their self-closed structures can encapsulate multiple drugs at once, protecting enclosed cargo from hydrolysis and breakdown. Additionally, targeting proteins and surface functional ligands on the outer shell of the lipid bilayer can add novel functionality—enabling targeted entry of liposomes into cells, either via antibodies or receptor-targeted ligands. These ligands attach to cell receptors that are over-expressed in certain diseased cells, allowing entry of the drug through the cell membrane.

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

Liposome Nanoparticle Production : Materials and Methods


How to produce liposome nanoparticles?

A stream of lipid in alcohol solution is surrounded by an aqueous phase within a glass capillary. The alcohol solution containing lipids diffuses into the aqueous solution (and reciprocally the water diffuses into the alcohol), until the alcohol concentration decreases to the solubility limit of the lipids. Consequently, this diffusion triggers the formation of liposomes by a mechanism described as “self-assembly”, where lipids assemble into a more energetically favorable structure. 

The liposome nanoparticles production system is illustrated in figure 2.

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

Partial results

liposome nanoparticles generation PBS
A liquid stream of ethanol with lipid, surrounded by PBS

LIPOSOME nanoparticles diameter according to the flow rate
Liposome mean diameter and polydispersity index (PDI) as a function of the flowrate 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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