Women today dream of recovering perfect skin and a glowing uniform complexion, with no marks or redness. Anticipating this desire, L’Oréal researchers developed the LR2412 molecule. This active ingredient was put on sale in 2011 first by Lancôme in the anti-age cream named Visionnaire. The development of this molecule is an illustration of L’Oréal’s predictive evaluation approach based on tests conducted on human reconstructed skin.
"Our research work was based on the expectations of women looking for a product able to act on lines, on the complexion and on the elasticity of the skin", explains Jean-François Michelet, head of L’Oréal’s biological and chemical evaluation laboratory. "Our aim was thus to find an anti-age molecule that could put off the possible need for plastic surgery as long as possible". The fruit of 12 years of research, the LR2412 molecule, protected today by 17 patents, is one of the major discoveries in cosmetology, capable of an overall effect on all skin characteristics, such as elasticity, resistance or pigmentation. Here is how this molecule was born, step by step.
The story starts in 2002. By observing the defense systems used by plants when attacked, the L’Oréal scientists examined Jasmonic acid, a molecule that activates healing of their tissues, while making them stronger."We knew that this chemical compound, Jasmonic acid, promoted regeneration of plant tissue", explains Jean-François Michelet. "We wondered whether such a chemical compound could also act in humans".
For the L’Oréal scientists, the challenge was then to identify similar molecules able, like in plants, to activate healing of tissues and make them stronger. In the fundamental research laboratory into Ageing, surface and hygiene at L’Oréal, the teams of Dominique Bernard selectively sorted and chose around twenty molecules.
Their selection was then sent to the Research Laboratory into biological active ingredients where the chemists entered the scene. "By observing the detailed chemical structure of the Jasmonic acid molecule, we found it interesting because it is both an acid and amphiphilic (1), two properties that promote the skin’s natural exfoliation process (elimination of dead epidermal cells) and hence its regeneration", explains Maria Dalko, head of the laboratory. After several months of work, the researchers ultimately selected the best two molecules, with LR2412 winning the race.
After evaluating the innocuousness of the molecule, "we then examined the effects of the molecule on the human dermis and epidermis", says Jean-François Michelet. "We wanted to evaluate its concrete effects". To do so, the researchers tested the molecule on reconstructed skin, manufactured in the Predictive Evaluation Center in Gerland, Lyon. This is where the effectiveness (real benefits) and innocuousness (absence of any toxic effects) of all molecules (or compounds) used in all L’Oréal products are evaluated.
Knowing that LR2412 had an effect on the surface, the scientists first used the Episkin reconstructed skin model. "A very thin epidermis used to test accurately the healing effect of a molecule", explains Jean-François Michelet. "We then observed the ability of this molecule to stimulate the renewal of the epidermis and studied its effect on the synthesis of hyaluronic acid (This molecule moisturizes and protects the skin from external attack, it holds water like a sponge and forms a protective aqueous film that diminishes over time). The production of hyaluronic acid in the body falls over time and is responsible for thinning of the skin".
The retinol is THE reference in the anti-aging. What is very remarkable, the retinol activity is pretty much the same as the LR2412 when it comes to the metabolism of the hyaluronic acid. Nevertheless, the LR2412 has better tolerance effects, due to the disturbed maturation of the upper layers of the epidermis. In parallel, tests indicated that the molecule did not change the protective functions of the skin that could lead to water loss or allergies, for example. After a year of evaluation, the three biologists working on the tests confirmed two qualities of LR2412: "the molecule promotes renewal of the epidermis and increases the synthesis of hyaluronic acid".
"We then worked on its chemical structure", explains Maria Dalko. Concretely, "we transformed some functions of the molecule to enable its beneficial properties to be expressed to the maximum". Human test protocols followed, conducted using a simplified formulation, in various age groups. Very short tests but which "enabled final validation of the anti-aging properties of the LR2412 molecule", says Jean-François Michelet. One last stage remained, which was essential. Designing a final formulation that would be able to create coherency between the real effectiveness of the product and the effectiveness perceived by the consumer.
Evaluations on the dermis, the deeper layer of the skin, could commence. This time, researchers used the Realskin model, which as its name indicates, reproduces "real skin" in three dimensions. "We were able to go further and measure the real anti-aging effects of the molecule", relates the head of L’Oréal’s biological and chemical evaluation laboratory. After a year of testing, "we were able to confirm that LR2412 was tolerated well by the skin, and we noted that it had an effect on the skin’s epidermal junction (area between the dermis and the epidermis and promoting adhesion between the two parts), which is closely linked to its mechanical resistance, and helps fight sagging of the tissues".
Pushing their investigations still further, the biologists measured the importance of certain compounds, called markers, in the skin. Result: LR2412 promotes the production of collagen, a protein that contributes to tissue resistance, and of fibrin, a compound that helps skin elasticity. The molecule was therefore an excellent candidate, as the expression goes, for the creation of a new cosmetic product able to stimulate a dozen or so biological markers. "Then we knew that we were on to a very interesting molecule", applauded Jean-François Michelet. It only remained to make a product.
The architects of formulation, scientists at Applied Research, were able to translate the predictive ability of LR2412. Thanks to Realskin, L’Oréal’s 3D reconstructed skin model, an optimal formulation was found, able to optimize the diffusion and distribution of the active ingredient in the three compartments of the skin (stratum corneum, epidermis, dermis).
A complex task to being with. Indeed, the LR2412 molecule, "which has a head that loves water and a tail that loves oil, didn’t know where to put itself in an emulsion!" laughed the L’Oréal laboratories. As oil and water are essential components in the formulation of a cosmetic product, a solution had to be found. By testing formulations on Realskin, scientists finally opted for a formulation in the form of a serum, offering the molecule "the best possible vehicle". And thus enabling it to express its cosmetic potential to the maximum.
"When we develop a product", explains Fabrice Aghassian, international director of evaluation methods for research, "we assemble elementary bricks (active ingredient, color, texture, etc.) based on the measurement of the molecule’s effectiveness, but which will be reinforced by sensory messages". "For example, an apple green skincare cream will not have the same perception of effectiveness as a honey-colored cream", indicates Fabrice Aghassian. This perception can vary with different age groups, methods of use or even culture. "Our goal is to combine what is relevant and expected", underlines the expert, "knowing that innovation in an end-product is both relevant to expectations and unexpected!" »
The L’Oréal laboratories are already looking to the future and the descendants of LR2412. "The potential of this molecule is leading us to look for new beneficial fields of use that meet women’s expectations, in particular with teams in the Consumer Insight department", explains Maria Dalko.
The exfoliating properties of LR2412 could for example lead us to create a formulation for "home peeling", i.e. a facial treatment for use in the home. A true scientific discovery, LR2412 could also be the first link in an entirely new generation of facial skincare products.
(1) Amphiphilic: amphiphilic molecules have the dual property of being attracted by water (hydrophilic) and by oil (lipophilic). Soaps are based on this property: the lipophilic part (fatty acid) fixes the organic molecules that water alone cannot remove, whereas the hydrophilic part is carried away by the water. This property thus promotes exfoliation.