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Liposomes

Liposome Components DiagramLiposomes are drug delivery vehicles that can be formulated with a wide variety of natural, synthetic, and modified lipid species to deliver drugs and contrast agents. There are 15 liposomal drug formulations on the market (as of 2017) for indications such as cancer, fungal infections, macular degeneration, pain management and vaccines. There are many applications using liposomes in clinical, preclinical, and basic research, including:

 

• Drug delivery
• Gene delivery/transfection
• Contrast agents for medical imaging (eg: ultrasound, MRI
and fluorescence)
• Precursors for lipid coatings (eg: biosensors)
• Model cell membranes


Key Benefits    How it works    Resources

Overcome Key Challenges in Advancing Liposome Formulations


Challenges with conventional methods  Solutions with the NanoAssemblr Platform
The formulation process has significant batch-to-batch variabilityorangeRightArrowReproducible liposome manufacturing conditions
Maintaining precise control over the particle size is difficultorangeRightArrowControl liposome size through instrument parameters
Loading liposomes requires multiple steps orangeRightArrowCombined drug loading and liposome formation in one step for efficient and versatile drug loading
Production is time-consuming and labor-intensiveorangeRightArrow
Rapid, effortless liposome production and optimization
The manufacturing process is difficult to scale-uporangeRightArrowA seamless path to scaling up production

Key Benefits


Reproducible Liposome Manufacturing Conditions


Liposome Reproducibility GraphLiposome size and polydispersity were consistent across six independent batches prepared by different operators.


Liposome Size Control Through Convenient Instrument Parameters

Liposome Size Control FRR
The effects of adjusting Total Flow Rate (TFR) and Flow Rate Ratio (FRR) in the NanoAssemblr® software on nanoparticle size. Parameters can be easily adjusted to achieve a specific size for a given lipid composition.


Combine Drug Loading and Liposome Formation in One Step for Efficient and Versatile Drug Loading

Rapid Formulation Development
Encapsulation efficiency of verteporfin loaded liposomes containing natural (egg-PC, soy-PC) or synthetic phospholipids (POPC, DSPC) as the primary lipid component.


A Seamless Path to Scaling Up Production

Small Molecule Scaleable
An example shown here is a liposome formulation (POPC/Cholesterol 60/40 mol/mol), optimized using the NanoAssemblr Benchtop and scaled up using the NanoAssemblr® Blaze™ and the 8x Scale-Up System with minimal process development and identical results.

How it works

NanoAssemblr Microfluidic Mixing



An organic solvent with dissolved lipids and an aqueous solution are injected into the two inlets of the NanoAssemblr® mixer. With laminar flow, the two solutions do not immediately mix. Microscopic features engineered into the channels cause the two fluids to intermingle in a controlled and reproducible way. Within 1 ms, the two fluids are completely mixed. This mixing causes a change in solvent polarity which triggers self-assembly of lipids into liposomes. Controlling the speed and ratio of fluid injection controls the size of the liposomes.


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Liposome Resources

Application Note

July 01, 2018

Seamless scale up of liposomal verteporfin formulations using the NanoAssemblr® Platform

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Publication - Abstract

April 26, 2018

Small Methods

State‐of‐the‐Art Design and Rapid‐Mixing Production Techniques of Lipid Nanoparticles for Nucleic Acid Delivery

Evers, M. J. W., Kulkarni, J. A., van der Meel, R., Cullis, P. R., Vader, P., & Schiffelers, R. M.

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Publication - Abstract

June 13, 2018

Bioconjugate Chemistry

Hyaluronic acid surface modified liposomes prepared via orthogonal aminoxy coupling: synthesis of nontoxic aminoxylipids based on ...

E Bartheldyova et al.

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Publication - Abstract

April 16, 2018

Acta Biomaterialia

Development of a Macrophage-Targeting and Phagocytosis-Inducing Bio-nanocapsule-based Nanocarrier for Drug Delivery

Li, H., Tatematsu, K., Somiya, M., Iijima, M., & Kuroda, S.

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Publication - Abstract

April 05, 2018

Advanced Drug Delivery Reviews

Transforming Nanomedicine Manufacturing toward Quality by Design and Microfluidics

Colombo, S., Beck-Broichsitter, M., Bøtker, J. P., Malmsten, M., Rantanen, J., & Bohr, A

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Publication - Abstract

March 19, 2018

Advanced Drug Delivery Reviews

Advances in Microfluidics for Lipid Nanoparticles and Extracellular Vesicles and Applications in Drug Delivery Systems

M. Maekia, N. Kimurab,Y. Satoc, H. Harashimac, M. Tokeshi

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