New Skin-Relevant Cell Coculture Model With Stratum Corneum-Like Layer.

Two-dimensional (2D) cell culture is an important tool in the discovery of skin-active agents. Fibroblasts and keratinocytes, more rarely fibroblast-keratinocyte cocultures, are usually used for that purpose, where test compounds are added by mixing with the overlaying growth medium. However, such an approach is suboptimal because it lacks the stratum corneum component. The stratum corneum acts as a selective gatekeeper and opposes the intradermal permeation of many compounds that are bioactive when placed in direct contact with cells. One solution is to use reconstituted epidermis, but this approach is costly and time consuming. Here, a model is proposed, where the simplicity and convenience of the 2D cell culture is combined with the advantage of a hydrophobic barrier reminiscent of the skin horny layer. This model was tested with skin-relevant solvents, as well as with "naked" hydrophilic and encapsulated compounds. Cell viability and collagen stimulation were used as readouts. The results showed that the incorporation of a stratum corneum-substitute barrier on top of a 2D cell culture reduced the cytotoxicity of a common cosmetic solvent, dimethyl isosorbide (DMI), in cell culture and modified the bioactivity of the added actives (magnesium ascorbyl phosphate [MAP] and oligomeric proanthocyanidins [OPCs]/levan biopolymer), which became dependent on their ability to penetrate through a lipidic layer. Taken together, these results indicate a better physiological relevance of this cell culture model in workflows aimed at the discovery and analysis of skin-active compounds than conventional 2D systems.

Synthesis and new skin-relevant properties of the salicylic acid ester of bakuchiol.

Bakusylan (bakuchiol salicylate) is a bipartite compound obtained by merging two skin-active entities with complementary bioactivities-bakuchiol and salicylic acid-for the purpose of generating a new class of functional retinoids with enhanced skin benefits. Here, we describe its preparation process and report that pure bakusylan exhibits potential for an improved permeation through the stratum corneum, enhances type IV collagen gene expression in organotypic skin substitutes containing both epidermal and dermal layers, and upregulates this protein in adult human dermal fibroblast cultures. The mechanism of action underlying these effects appears to involve the components of the IP3K/Akt signaling pathway selectively implicated in the maintenance of skin integrity, further underlying the suitability of this ester for skin care applications requiring enhanced cutaneous permeation targeting the dermal-epidermal junction.

Tetrahexyldecyl Ascorbate (THDC) Degrades Rapidly under Oxidative Stress but Can Be Stabilized by Acetyl Zingerone to Enhance Collagen Production and Antioxidant Effects.

Tetrahexyldecyl Ascorbate (THDC) is an L-ascorbic acid precursor with improved stability and ability to penetrate the epidermis. The stability and transdermal penetration of THDC, however, may be compromised by the oxidant-rich environment of human skin. In this study, we show that THDC is a poor antioxidant that degrades rapidly when exposed to singlet oxygen. This degradation, however, was prevented by combination with acetyl zingerone (AZ) as a stabilizing antioxidant. As a standalone ingredient, THDC led to unexpected activation of type I interferon signaling, but this pro-inflammatory effect was blunted in the presence of AZ. Moreover, the combination of THDC and AZ increased expression of genes associated with phospholipid homeostasis and keratinocyte differentiation, along with repression of MMP1 and MMP7 expression, inhibition of MMP enzyme activity, and increased production of collagen proteins by dermal fibroblasts. Lastly, whereas THDC alone reduced viability of keratinocytes exposed to oxidative stress, this effect was completely abrogated by the addition of AZ to THDC. These results show that AZ is an effective antioxidant stabilizer of THDC and that combination of these products may improve ascorbic acid delivery. This provides a step towards reaching the full potential of ascorbate as an active ingredient in topical preparations.