Development of Transdermal Absorption Technology Based on Multilayered Liposomes

*Edelweiss Callus Culture Extract, Dulse Extract, Saccharina Longicruris Extract, Alteromonas Ferment Extract, Rosa Izei Extract, Bilberry Extract, Geranium Robertianum Extract, Artichoke Leaf Extract, 3-O-Ethyl Ascorbic Acid, Niacinamide, Hexacarboxymethyl Dipeptide-12, Trifluoroacetyl Biotinyl Histidyl D-Tryptophanyl Dipeptide-29. Elm Japan Co., Ltd. (Headquarters: Shibuya-ku, Tokyo; CEO: Emi Sakuoka), based on its expertise in dermatology and formulation research, has developed a new transdermal absorption technology using multilayered liposomes as carriers. This technology aims to encapsulate active ingredients with various physical properties and, in particular, to reliably deliver components that are difficult for transdermal absorption (stratum corneum penetration), such as water-soluble ingredients, into the skin. Achievements with this technology: - Development of formulations with high concentrations of multilayered liposomes based on evidence. - Realization of deep skin penetration for poorly-permeating ingredients using multilayered liposomes. - Construction of a formulation system that achieves a high-実感 (high-sensation) experience. Research Background: Humans are maintained by a complex life reaction called homeostasis. Therefore, to bring about specific effects on the skin, such as wrinkle improvement, it is considered important to simultaneously activate (or inhibit) complex reaction pathways. In recent years, topical preparations like cosmetics have been designed to target these complex life reactions by combining multiple functional ingredients for a multi-faceted approach to improvement. However, each ingredient has different physical properties, leading to challenges with variations in skin absorption behavior and dispersion within the skin. Focusing on this issue, our company has undertaken the development and verification of this technology to achieve the design philosophy of 'delivering ingredients as a unified group' rather than 'delivering them individually.' Features and Solutions of This Technology: Confirmation of Multilayered Liposome Existence: Multilayered liposomes have a structure of multiple concentric lipid bilayers. While liposomes can encapsulate hydrophilic components in their internal aqueous phase and hydrophobic components in the lipid membrane, the multilayer structure allows for the organized arrangement of multiple components within a single carrier, promising increased design flexibility in mixture formulations. We have successfully scientifically verified the existence of multilayered liposomes in this technology. Generally, the spherical shape and lipid membrane coating are crucial elements for liposomes. However, simple particle size measurements cannot assess the membrane state or spherical nature, and thus do not necessarily confirm the existence of liposomes. In this study, by using a transmission electron microscope (TEM), we were able to verify that these liposomes have a spherical structure and are composed of multiple layers. This suggests that the liposomes constructed in this study are highly likely to be in a functional state. Confirmation of Deep Skin (Dermis) Penetration for Difficult-to-Penetrate Water-Soluble Ingredients: To confirm the key function of skin permeability in liposomes, we used the model component calcein and the water-soluble compound nicotinamide as model compounds, formulated them into liposomes, and performed permeability evaluation using a skin model. The results confirmed that the formulation with multilayered liposomes allowed the model components to penetrate to the dermis (qualitative evaluation, Figure 2) and that, quantitatively, the skin permeability of nicotinamide was significantly enhanced compared to a formulation without liposomes (quantitative evaluation, Figure 3). From these results, it has been scientifically proven that the technology developed in this study consists of functional multilayered liposomes and is a technology that can promote transdermal absorption deep into the skin. Based on these findings, our company will further research how multiple ingredient complexes affect skin mechanisms to deepen the effects achieved by this transdermal absorption technology. Furthermore, we will not only apply this technology to commercial products but also promote its use in a wide range of new products, including skincare and scalp care.