The pros and cons of the systemic and topical application of antioxidant substances are a subject of intense discussion among experts, with resulting confusion for consumers and producers. The objective of the present article is to clarify the various uncertainties relating to the use of antioxidant substances in dermatology. Whereas inappropriate application of antioxidant substances (concerning their concentration and composition) might induce harmful effects, the consumer will definitively benefit from physiological concentrations and compositions of antioxidants. The most suitable method is the consumption of natural antioxidants in the form of fruit and vegetables, for example. In addition, the skin, which also accumulates antioxidant substances, may profit from a sufficient antioxidative level, as damage induced by sun radiation in addition to skin aging is reduced.

Topical glucocorticoids (GCs) demonstrate good anti-inflammatory effects but are limited by their side effect potential, with skin atrophy being the most prominent one. Thus, determining the atrophogenic potential of novel compounds is important. The aim of this study was to establish an in vitro skin atrophy model. A screening cascade was applied and GCs with a known atrophogenic potential were used as tool compounds. Five rodent and human cutaneous cell types/cell lines and 2 human skin equivalents were tested. Known and suspected atrophy markers related to collagen metabolism and epidermal thickness were measured. Altogether, a combination of 7 different cellular assays with up to 16 markers each were investigated. A reproducible, more than 2-fold, regulation of the candidate markers by dexamethasone or clobetasol was found for: (a) matrix metalloproteinase <i>(MMP) 1, 2, 3</i> and <i>9</i> expression in human keratinocytes, (b) <i>COL1A1</i> and <i>COL3A1</i> expression in 3T3 fibroblasts, and (c) epidermal thickness, collagen and MMP synthesis in the full-thickness skin model (FTSM). These 3 models were further investigated with a panel of 4–5 GCs, demonstrating dose dependency and correlation with the atrophogenic potential of the tool compounds, qualifying them as potentially suitable. Finally, the predictability of these models for the in vivo situation was analyzed, testing a novel selective GC receptor agonist (SEGRA) in comparison to clobetasol. The results from the in vitro models suggested less atrophogenic effects for the SEGRA compound, which indeed was confirmed in the <i>hr/hr</i> rat skin atrophy model. In conclusion, a combination of 3 in vitro models based on 3T3 cells, human keratinocytes and FTSM with several readouts is recommended to determine atrophogenicity of GC receptor ligands. Further experiments are necessary to eventually reduce this panel and to demonstrate the true predictability for the clinic.

In the past, it was assumed that the intercellular route was the only relevant penetration pathway for topically applied substances. Recent results on follicular penetration obtained at the Center for Experimental and Applied Cutaneous Physiology, Charité – Universitätsmedizin Berlin, Germany, emphasize that the hair follicles represent a highly relevant and efficient penetration pathway and reservoir for topically applied substances.

<i>Background:</i> The skin is exposed to numerous environmental assaults that can lead to premature aging. Of these agents, perhaps none is more ubiquitous than the ultraviolet (UV) wavelengths of sunlight. The primary immediate defense against environmental skin damage is the antioxidant capacity of the skin. However, this defense system can be compromised by moderate exposure to UV light. Therefore, bolstering the antioxidant defense system of the skin is a potentially important strategy for reducing environmentally induced skin damage. <i>Aim of the Study:</i> This clinical trial was designed to study the efficacy of lutein and zeaxanthin, two potentially important antioxidants found naturally in the skin, upon five skin physiology parameters (surface lipids, hydration, photoprotective activity, skin elasticity and skin lipid peroxidation – malondialdehyde) of human subjects. These xanthophyllic carotenoids were administered either orally, topically, or in combination (both oral and topical routes). <i>Results:</i> The results obtained indicate that the combined oral and topical administration of lutein and zeaxanthin provides the highest degree of antioxidant protection. However, oral and topical administration of these antioxidants individually also provides significant activity in the skin. In addition, oral administration of lutein may provide better protection than that afforded by topical application of this antioxidant when measured by changes in lipid peroxidation and photoprotective activity in the skin following UV light irradiation.

Nanoparticles represent an important drug carrier system. Recently, we have reported on the penetration and storage behavior of particular and non-particular substances revealing the superiority of particular substances in the range of 300–400 nm. In this regard, it was assumed that the rigid hair shaft acts as a geared pump, moving the particles deeper into the hair follicle. In the present investigation, the storage reservoir capacity of the stratum corneum and the hair follicle infundibulum and canal are compared. Interestingly, we could demonstrate a 10 times longer storage within the hair follicles. These results underscore the importance of the hair follicle for drug delivery purposes, mainly highlighting new possibilities for the future concerning retarded delivery, application frequency, and galenic design.

With the help of a new ‘UVA stress model’, it was shown that Ectoin protects the skin from the effects of UVA-induced cell damage in a number of different ways. Using cell cultures, high-performance thin-layer chromatography, gel electrophoresis mobility shift assays, reverse transcriptase polymerase chain reaction, ion exchange chromatography and UV spectroscopy, it was demonstrated that the UVA-induced second messenger release, transcription factor AP-2 activation, intercellular adhesion molecule-1 expression and mitochondrial DNA mutation could be prevented. The results obtained clearly demonstrate that Ectoin counteracts the effects of UVA-induced and accelerated skin aging at different cell levels.