Esther Schnetz

High molecular compounds (polysaccharides and proanthocyanidins) from Hamamelis virginiana bark: influence on human skin keratinocyte proliferation and differentiation and influence on irritated skin.

Although extracts from Hamamelis bark have long been used in therapy of skin diseases and in cosmetic formulas there are only few pharmacological investigations verifying the activity of distinct Hamamelis bark constituents. Therefore two major classes of constituents, namely polymeric proanthocyanidins and polysaccharides were isolated from Hamamelis bark and tested concerning their influence on proliferation and differentiation of cultured human keratinocytes. While the polysaccharide fraction, consisting mainly of arabans and arabinogalactans, did not effect human keratinozytes, the proanthocyanidins strongly increased the proliferation of the cells, while the differentiation was not influenced significantly. Within a preliminary cumulative in vivo study on SLS-irritated skin, proanthocyanidins (ProcyanoPlus) were proven to reduce transepidermal water loss and erythema formation. Furthermore, a clinical scoring indicated that procyanidins can influence irritative processes significantly.

Microdialysis for the evaluation of penetration through the human skin barrier : a promising tool for future research?

The direct measurement of local drug concentration levels at discreet skin locations with minor trauma has recently become possible with the introduction of cutaneous microdialysis. Cutaneous microdialysis is an in vivo sampling technique for measuring solutes in the extracellular fluid of the dermis. When used in combination with other experimental approaches, for example with a variety of non-invasive techniques to describe the functional status of the skin (bioengineering methods), it may help investigators to gain new insights into the fields of skin diseases, metabolism and drug absorption/penetration. An important parameter to describe the efficacy of microdialysis is the relative recovery. This is the ratio between the concentration of a substance in the dialysate and the true extracellular concentration. Several methods are in common use to describe the relative recovery (no-net-flux method or retrodialysis). Parameters such as probe design, depth of the probe in the dermis, physico-chemical properties of the compound of interest, and analytical aspects are important factors influencing microdialysis. Microdialysis has been used to investigate the influence of penetration enhancers, vehicles or iontophoresis on percutaneous absorption, performed by in vivo studies in rats. In human volunteers, most of the experiments have been performed to study the kinetics of fast penetrating substances, e.g. nicotine, non-steroidal antiinflammatory drugs, local anaesthetics, or solvents. Problems have been encountered in the detection of lipophilic and highly protein-bound substances. Further, dermal metabolism and the influence of barrier perturbation on percutaneous absorption have been analyzed. Investigations suggest that microdialysis, in combination with traditional techniques, might give valuable information regarding the assessment of the penetration of drugs and other exogenous agents through the skin. In spite of the clearly defined and accepted advantages of microdialysis technology for studies of transdermal drug delivery, to date no standardized test procedure exists nor has the reproducibility of the results been evaluated. In the future, these problems have to be solved to enable this method to find its place in standard research.

Multicentre study for the development of an in vivo model to evaluate the influence of topical formulations on irritation

Although skin protective products to prevent irritant skin reactions are in wide use, neither standardized test models to prove differences in efficacy exist, nor has the quality or the reproducibility of results been evaluated in a multicentre approach. This should be mandatory when developing or testing skin care products. Therefore, we have designed a multicentre study in an approach to find a standardized test procedure for the evaluation of skin protective products. In this irritation study, a repeated short‐time occlusive irritation test (ROIT) with a standardized protocol has been evaluated in 2 phases (12 days and 5 days protocol) in 4 (n=20) respectively 6 (n=33) skilled centres. The skin reaction was induced by 2 irritants (0.5% aq. SLS and toluene, 2× a day for 30 min). Its modification by 3 different cream bases with different hydrophilicity was analyzed. The irritation was monitored by bioengineering methods (TEWL measurement, colorimetry) and by clinical scoring. The evaluation showed that significant results could already be achieved with the 5‐day protocol. Furthermore, in spite of the expected inter‐centre variations due to heterogeneity of the individual threshold of irritation, interpretation of clinical score, and inter‐instrumental variability, the ranking of the vehicles regarding reduction of the irritant reaction was consistent in all centres.

Does sodium lauryl sulfate concentration vary with time

When performing skin irritation tests with sodium lauryl sulfate (SLS), the quality of the test solution is of major importance for the reproducibility and comparability of the results. The influence of 4 different storage parameters (concentration, duration, temperature, material of the storage vials) on the stability of aqueous SLS solutions was investigated under non‐sterile conditions. SLS solutions at 5 different concentrations (0.001%, 0.01%, 0.1%, 0.5%, 1%) were analysed by mobile phase ion chromatography. Analyses were performed after a storage time of 3 h, 1 week, and 4 weeks. Storage was carried out at different temperatures: −18°C, 6°C, and 23°C. The storage containers were of 2 different materials (glass and polypropylene). After a storage of 1 week, no decrease in SLS concentration was observed, regardless of the chosen conditions. After 4 weeks at 6°C and 23°C, the SLS concentration was found to be significantly decreased for the 2 lowest concentrations (0.001% and 0.01%). At higher concentrations and lower temperatures, no decrease in SLS concentration had occurred. In parallel to the loss of SLS, contamination with bacteria was found in the solutions, especially at the 2 lowest concentrations. Bacterial growth was not observed at higher concentrations. The possibility of biodegradation of SLS has to be taken into account, especially when dealing with low concentrations of SLS.