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The Microfluidic Production of Liposomes: Key Issues

What are Liposomes

Liposomes are artificially created, microscopic, spherical structures that take a page from nature to exploit certain useful properties found in living cells. Their design enables them to excel at the targeted delivery of payloads, such as chemotherapeutic drugs delivered to tumor cells. Their defining characteristic is a lipid bilayer, consisting of phospholipids, such as phosphatidylcholine, which encase one or more substances of interest (such as chemotoxic drugs).

Nature knows best

The lipid bilayer that defines artificial liposomes mimics the similar lipid bilayer architecture that comprises living cell membranes. It's an ingenious design. It affords cells relatively strict control over what entities are able to enter — or leave — the safe confines of the cell. Think of it as tight border control.

Depending on the lipids used, and the orientation of hydrophobic or hydrophilic heads or tails, liposomes can be designed to resist interference from the immune system — or to protect healthy cells from the toxic payload — in order to enhance drug delivery. Until recently, this has been the most notable and promising use of this emerging technology. Liposomes have helped to magnify the efficacy — while reducing the toxicity — of chemotherapeutic drugs, for example. This has been a boon in the ongoing war against cancer.

But liposomes have numerous other potential uses. Biologically active molecules ranging from anti-cancer and anti-microbial agents to chelating agents, peptides, hormones, enzymes, proteins, vaccines and genetic materials have all come under consideration for delivery by synthetic liposomes. Exploiting this promising technology represents something of a modern gold rush among players in the biotechnology arena.

Beyond Chemotherapeutics

More recently, manufacturers have enlisted the advantages of liposomes to significantly enhance the bioavailability of various nutrients, nutraceuticals and cosmeceuticals. Bioavailability is a thorny issue for the nutraceutical industry. For example, while many compounds (such as curcumin — from the culinary herb turmeric) have been shown to possess remarkably promising biological activities (such as potent antioxidant and anticancer activities), it is notoriously difficult to get curcumin from the digestive tract into the bloodstream. Without reaching the bloodstream for dissemination throughout the body, the great majority of orally ingested curcumin goes to waste.

By enrobing such low-bioavailability substances in liposomes, it's possible to bypass some of the pitfalls of passing through the digestive tract, and to enhance delivery to the bloodstream. Thus, more of the beneficial compound is “bioavailable.” Without clever liposome packaging, the great majority of curcumin consumed would otherwise be flushed from the body through the kidneys or bowels without ever reaching the bloodstream. This is a problem plaguing any number of promising substances.


As the technology has progressed, clever process engineers have learned to tweak the designs of these ingenious delivery vesicles so that more than one payload may be delivered simultaneously — by loading a lipid-soluble drug within the bilayer, for instance, while also loading an aqueous core with a primary chemo-toxic drug. By studying the surface of the structure with targeting ligands, such as peptides, it's possible to tailor these biological “smart bombs” so that they possess an enhanced affinity for target cells.

Most often, this means they attach themselves specifically to aberrant, cancerous cells while leaving healthy cells alone. Among other benefits, this technology offers the flexibility to build in specific desirable features to further enhance the usefulness and efficacy of these structures.

Key Benefits

Liposomes offer many advantages:

  • Stabilization of bioactive materials (the “payload”) against a variety of chemical and environmental challenges
  • Enhancement of bioavailability
  • Greatly reduced side effects compared to cruder, shotgun-style approaches to the delivery of chemo-toxic drugs
  • Controlled, time-released delivery for enhancement of efficacy
  • Enhanced shelf life

Key challenges related to the design and production of liposomes

Typical medical-use liposomes fall within the size range of about 100 nm in diameter. Producing these delivery vehicles, known as “nanoscale lipid-based vesicular systems,” presents challenges for process engineers. Their large-scale production is typically achieved using microfluidic techniques. Issues related to production include:

  • Lipid formulation
  • Lipid concentration
  • Residual solvent retention
  • Production method (including microchannel architecture)
  • Drug loading

Note that microchannel architecture is a key determining factor.  Microfluidizer® processors excel at biomedical and biotechnological applications, not least because our proprietary microchannel architecture maximizes shear forces under a wide range of pressures. This helps deliver tight particle size distribution curves, using less energy and requiring fewer passes. Even better, we guarantee smooth scale-up from investigatory runs to full-production runs.

For more information about how Microfluidizer® technology can improve your bottom line, contact us here, or fill out our online quote form.

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Posted by Steve Mesite
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