The vitamin A ester retinyl propionate has a unique metabolic profile and higher retinoid-related bioactivity over retinol and retinyl palmitate in human skin models.

Human skin is exposed daily to environmental stressors, which cause acute damage and inflammation. Over time, this leads to morphological and visual appearance changes associated with premature ageing. Topical vitamin A derivatives such as retinol (ROL), retinyl palmitate (RPalm) and retinyl propionate (RP) have been used to reverse these changes and improve the appearance of skin. This study investigated a stoichiometric comparison of these retinoids using in vitro and ex vivo skin models. Skin biopsies were treated topically to compare skin penetration and metabolism. Treated keratinocytes were evaluated for transcriptomics profiling and hyaluronic acid (HA) synthesis and treated 3D epidermal skin equivalents were stained for epidermal thickness, Ki67 and filaggrin. A retinoic acid receptor-alpha (RARα) reporter cell line was used to compare retinoid activation levels. Results from ex vivo skin found that RP and ROL have higher penetration levels compared with RPalm. RP is metabolized primarily into ROL in the viable epidermis and dermis whereas ROL is esterified into RPalm and metabolized into the inactive retinoid 14-hydroxy-4,14-retro-retinol (14-HRR). RP treatment yielded higher RARα activation and HA synthesis levels than ROL whereas RPalm had a null effect. In keratinocytes, RP and ROL stimulated similar gene expression patterns and pathway theme profiles. In conclusion, RP and ROL show a similar response directionality whereas RPalm response was inconsistent. Additionally, RP has a consistently higher magnitude of response compared with ROL or RPalm.

Association Between Skin Acid Mantle, Natural Moisturizing Factors, and Antibacterial Activity Against S. aureus in the Stratum Corneum.

Purpose: The skin has evolved a system to prevent pathogenic microorganism colonization and infection. This study examined the role of natural moisturizing factors (NMFs) and skin pH on Staphylococcus aureus (S. aureus) growth and colonization on the human stratum corneum (SC). Study Population and Methods: A survey study with 82 female participants was performed. Participants maintained their daily hygiene routine, except for refraining from using leave-on products on their forearms on the day of the test. Skin sampling was performed using adhesive tapes. An ex vivo method was developed to study the viability and growth of S. aureus on human SC sampled from normal skin. NMFs, including pyrrolidone carboxylic acid (PCA), urocanic acid (UCA), histidine, and proline in SC samples, were measured by liquid chromatography with tandem mass spectrometry. The impact of PCA and UCA on S. aureus growth and metabolic activity was measured by optical density and isothermal microcalorimetry, respectively. Results: Heterogeneity of S. aureus viability on human SC samples was observed. Skin pH showed a significant negative association (p<0.05) with SC antibacterial activity in the ex vivo assay. One unit of skin pH decrease corresponded to 68.1% of S. aureus cell death. The levels of PCA and histidine were significantly negatively associated (p<0.05) with skin pH. The addition of 5 mM and 10 mM PCA significantly inhibited S. aureus growth by approximately 25% at 20 hours and reduced its metabolic activity in vitro. Conclusion: The results indicate that PCA, one of the NMFs in human skin, plays an important role in regulating the human skin acid mantle in vivo and contributes to antibacterial activity against S. aureus.