Liposomes

What Are Liposomes?

Structure of a liposome

Liposomes are microscopic capsules of multilayered phospholipids found in our skin that range from 0.1 – 0.2μm in size (0.1μm is 1/10,000th of 1 mm). Phospholipids have a hydrophilic (water-loving) head and a hydrophobic (water-fearing) tail, arranged as shown in the figure to the right to create a multilayered structure much like an onion. Phospholipids are an excellent transport technology in pharmaceutical applications, as drugs can be encapsulated within the phospholipid for delivery into the body.

The History of KOSÉ’s Cosmetic Liposome Development

Electron microscope image of a liposome

Cosmetic liposome development began at KOSÉ in 1984, when one of our researchers became fascinated with the beautiful onion-like layers of liposomes after attending a pharmaceutical conference. At the time, stabilizing liposomes in cosmetic formulations was difficult, and it was considered impossible to formulate multilayered liposomes for use in cosmetics. This researcher enthusiastically continued to pursue liposome research and, after eight years of trial and error, was able to demonstrate their stability and benefits in cosmetics and create a successful formulation. KOSÉ laboratories have continued their liposome research for more than 30 years, working toward even higher efficacy.

The Science of Liposomes

How do liposomes work in the skin? As shown in the figure below, skin has a layered structure. The stratum corneum is the outermost layer and one of the most important parts of the skin barrier, preventing the entry of foreign substances and preventing moisture escape.

An enlarged view of the stratum corneum also reveals the presence of intercellular lipids. These intercellular lipids consist of alternating layers of hydrophilic heads and hydrophobic tails stacked like a mille-feuille cake; in scientific terms, this is called a “lamellar structure.”

For healthy skin, it is necessary that both stratum corneum cells and intercellular lipids are in a normal state.

  • Structure of skin
  • Structure of skin (electron microscope image)

Research Report 1

Discovering That Liposomes Form a Lamellar Structure on the Skin

Our researchers found that applying liposomes to the skin helps form lamellar structures that are important to skin barrier functioning.

This finding came from a detailed structural analysis of the skin following liposome application and was confirmed using the SPring-8, large-scale synchrotron radiation facility in Japan. Observation with electron microscopy also revealed that more lamellar structures were formed when liposomes were applied. (Photograph)

The conclusion was that liposomes work by reinforcing the skin’s inherent barrier function.

Lamellar structures formed between stratum corneum cells (electron microscope image)

Comments from Researcher

Searching for New Effects on the Skin

In researching the relationship between liposomes and skin, my approach has been that we need to understand more about how liposomes affect the skin in order to develop even better ones! It occurred to me that liposomes themselves could form lamellar structures, but I also had a difficult time proving it with research.

Through ongoing discussions of the matter with various specialists in surfactant chemistry, dermatology and physics, I was able to mobilize their specialized knowledge to finally prove that liposomes create a new effect on the skin.

This research was selected for the Best Presentation Award at the 87th Research Symposium of the Society of Cosmetic Chemists of Japan (SCCJ) in 2021.

Research Report 2

Visualizing Liposome Water Retention Structure in the Stratum Corneum

Electron microscopy visualization techniques are essential to liposome R&D. Such techniques have been used to prove that liposomes are structured in multiple layers like an onion and to observe changes in the skin following application of liposome formulations.

One example of this work is a visualization of the water retention structure (expansion from hydration) in the stratum corneum after applying a liposome formulation.

Ordinarily, it is difficult to observe a hydrated object as is. However, our researchers used cryogenic scanning electron microscopy (CryoSEM) techniques to obtain detailed images, which revealed that applying a liposome formulation resulted in a water retention structure (expansion from hydration) in the middle-to-lower layers of the stratum corneum.

These results show that liposome application helps retain moisture deep into the stratum corneum.

  • Formation of water retention structure in stratum corneum (electron microscope image)
  • Formation of water retention structure in stratum corneum (electron microscope image)

Comments from Researcher

Electron Microscopy Techniques for Liposome Research

We have used electron microscopy right from the start of our liposome R&D, developing our own visualization techniques such as the one shown in the video below. This beautiful multilayer structure makes liposomes uniquely attractive.

Visualization techniques are also indispensable in terms of proving functionality. The visualization of water retention structures in the stratum corneum is one example, and such approaches involve manipulations and techniques that cannot be described in a manual.

I will continue embrace visualization techniques that surprise and convince others at a glance because I am an electron microscope technician who understand cosmetics.

3D-structural image of a liposome (blue: hydrophilic head, yellow: hydrophobic tail)

Research Report 3

Successfully Increasing Liposome Concentrations

Liposome research is not limited to skin effects. It also develops formulations that maximize the value of a single drop of product. One example of such research is the development of high-concentration liposomes.

In the early days of liposome research, high-concentration liposomes were not stable as the liposomes would collide and degrade their structure. KOSÉ researchers reconsidered the components of the liposomal membrane, developing a new formulation that controls membrane fluctuations for a strong membrane that does not collapse with collisions.

This discovery allowed researchers to create formulations with higher component concentrations and higher efficacy.

  • Image of improved liposome membrane strength
  • Issues with high liposome concentrations (schematic)

Comments from Researcher

The Hidden Possibilities of Liposomes in Formulation Research

Since its beginnings, cosmetic liposome research has continued to grow without waning. However, there have been many difficulties in realizing high concentrations for enhanced effectiveness.

There are only a limited number of materials available to properly construct liposomes, so we tried different combinations and adjusted manufacturing temperatures and times in order to create not just a multilayered liposome but one that can hold up over an extended period.

When we finally achieved a high concentration, I was once again fascinated with charms of liposomes—that they contain hidden possibilities. I will continue my research to evolve liposomes!

R&D Strengths