Klaus-P. Wilhelm

Skin Aging: Effect on Transepidermal Water Loss, Stratum Corneum Hydration, Skin Surface pH, and Casual Sebum Content

This study investigates the effect of cutaneous aging on transepidermal water loss, stratum corneum hydration (capacitance), skin surface pH, and causal sebum content. Because the physiologic condition of skin varies considerably with anatomic region and skin aging might demonstrate regional variability, all factors were studied on 11 anatomic locations in 14 young adult (seven female and seven male subjects; 26.7 +/- 2.8 years [mean +/- SD]) and 15 aged human volunteers (seven female and seven male subjects; 70.5 +/- 13.8 years). Significant anatomic variability was noted for all factors in both age groups. However, no significant differences between the two groups were noted for sebum, capacitance, and pH on most anatomic regions. Transepidermal water loss, however, was significantly lower in the aged population on all anatomic regions tested, except for the postauricular region and the palm. Comparing male and female volunteers, none of the four factors showed significant differences. Of all measured factors, only transepidermal water loss showed significant age-related differences on most anatomic regions studied. The additionally observed differences between the age groups on the ankle for pH and sebum might be related to the stasis frequently observed on the lower limbs in aged individuals.

Frictional properties of human skin: relation to age, sex and anatomical region, stratum corneum hydration and transepidermal water loss.

Differences in the dynamic skin friction coefficients (μ) were investigated with respect to age, sex, and anatomical region. A total of 29 volunteers consisting of seven young females, seven old females, seven young males, and eight old males participated in the study. Measurements were obtained from II anatomical regions, namely, the forehead, upper arm, volar and dorsal forearm, postauricular, palm, abdomen, upper and lower back, thigh, and ankle. The friction data were compared with stratum corneum hydration and transepidermal water loss (TEWL). The dynamic friction coefficient did not vary significantly between age and sex groups but varied considerably among the anatomical regions of the body. The forehead and postauricular had the highest μ (0.34 ± 0.02) while the abdomen had the lowest (0.12 ± 0.01); the remaining regions had an average μ value of 0.21 ± 0.01. Similarly, no sex differences were observed for TEWL and stratum corneum hydration. Capacitance was only significantly lower on the palms of the elderly. Regional differences showed a higher state of hydration on the forehead and postauricular as well as the upper arm, upper and lower back when compared with the volar forearm. TEWL was generally lower in the elderly on all anatomical regions except the postauricular and palm. A significant correlation was established between μ and capacitance for most regions. Between μ and TEWL significant correlation was observed only on the palm and thigh. These findings suggest that frictional properties of skin are dependent on more than water content or non‐apparent sweating and the role of sebum secretion is suggested as one possible factor.

Cutaneous sodium lauryl sulphate irritation potential: age and regional variability

To investigate differences in response to irritation according to age and site seven young‐adult and eight elderly females were exposed to 0.25% sodium lauryl sulphate (SLS) under patch‐test occlusion for 24 h. Ten anatomical regions were tested: forehead, upper arm, volar and dorsal forearm, postauricular, palm, abdomen, upper back, thigh, and ankle. The skin responses were evaluated 24 h post‐patch removal by visual scoring and by transepidermal water loss measurements (TEWL). Non‐treated symmetrical anatomical regions served as controls. SLS induced a mild erythematous reaction on most anatomical regions except the palm and TEWL was significantly increased as compared with controls. The elderly group demonstrated significantly less susceptibility to SLS‐induced irritation for most regions of the body as indicated by visual scores and TEWL measurements. In addition, evaluation of the stratum corneum water content following SLS irritation demonstrated lower responses in the old age group for most regions. The thigh had the highest reactivity and the palm the lowest, in both age groups. These data suggest that young adult skin is more sensitive to SLS than old skin and that SLS irritation varies considerably with respect to region. Moreover, objective TEWL measurements seem to be a better indicator of irritant susceptibility, especially in the elderly, than clinical evaluation by visual scoring.

Surfactant-induced skin irritation and skin repair: Evaluation of a cumulative human irritation model by noninvasive techniques

BACKGROUND Although surfactant-induced acute irritant dermatitis has been extensively studied, our understanding about the induction and repair of the clinically more relevant chronic form is limited. OBJECTIVE Our purpose was to investigate qualitative and quantitative differences in surfactant-induced irritant skin reactions from cumulative exposure to structurally unrelated surfactants and to compare the maximal irritant responses from this model with corresponding reactions noted in a previously reported acute irritation model. METHODS Sodium lauryl sulfate (SLS), dodecyl trimethyl ammonium bromide (DTAB), and potassium soap were the model irritants. Surfactant solutions (7.5%) were applied for 20 minutes daily (for 8 consecutive days excluding the weekend) to the volar aspect of the forearm of 11 volunteers. Irritant reactions were repeatedly assessed until complete healing was indicated by visual assessment and by measurements of transepidermal water loss (TEWL), erythema (skin color reflectance), and stratum corneum hydration (electrical capacitance). Maximum irritant responses were compared with corresponding reactions from an acute irritation model. RESULTS TEWL was increased by SLS and DTAB to the same extent, but erythema was significantly higher in DTAB-treated skin. Skin dryness, as demonstrated by decreased capacitance values and increased scores for scaling and fissuring, was significantly more pronounced than in an acute irritation model for SLS and DTAB, although no difference was detected between the two surfactants. Potassium soap led to a slight increase in TEWL, whereas the remaining features were not significantly changed. CONCLUSION This chronic irritation model appears to represent the clinical situation of irritant contact dermatitis with pronounced skin dryness more closely than the acute irritation model. The present study confirms that an extended time is needed for complete healing of irritant skin reactions. We also demonstrated that the evaluation of the irritation potential of diverse surfactants depended significantly on the feature evaluated (erythema vs electrical capacitance and TEWL), on the mode of application (acute vs cumulative), and, in the cumulative model, on the point of observation.

Optimization of Topical Therapy: Partitioning of Drugs into Stratum Corneum

To optimize a topical formulation for therapeutic effect generally implies that the flux of drug into the skin be maximized. This requirement means that the product of drug concentration in the vehicle (Cv) and drug partition coefficient (PC) between stratum corneum (SC) and vehicle be as large as possible. While Cv is a formulation variable which can be easily manipulated up to the drugs saturation solubility, PC is a parameter that is difficult to predict a priori. However, there is no question that an ability to evaluate PC would greatly facilitate the efficient screening of drugs and formulations. We have measured the SC/water and SC/isopropylmyristate (a model lipophilic vehicle) PCs of seven drugs: acitretin, progesterone, testosterone, diazepam, estradiol, hydrocortisone, and caffeine. SC/ water PCs were determined as a function of the following variables: (i) initial drug concentration in the vehicle, (ii) length of equilibrium, (iii) SC source and preparation technique, and (iv) SC delipidization. The data obtained were reproducible and physicochemically consistent, and they show that useful partitioning information from both aqueous and nonaqueous vehicles can be obtained with the biological tissue of greatest relevance. The SC/water PCs of the steroids were in reasonable agreement with previous measurements. A facile approach to an integral determinant of formulation optimization is suggested, therefore, by these observations.

Skin Surface Lipid and Skin Friction: Relation to Age, Sex and Anatomical Region

Differences in the skin surface lipid content (SSL) and the dynamic friction coefficient (mu) were investigated with respect to age, sex, and anatomical region in 29 volunteers. The group consisted of (a) 7 young adult females (24.9 +/- 1.1 years old, mean +/- SD), (b) 7 old females (75.3 +/- 2.4 years old), (c) 7 young adult males (28.7 +/- 0.5 years old), and (d) 8 old males (73.8 +/- 1.9 years old). Measurements were obtained on 11 anatomical regions, namely, the forehead, upper arm, volar and dorsal forearm, postauricular, palm, abdomen, upper and lower back, thigh, and ankle. Skin surface lipid content data were compared with mu measurements to determine the relative contribution of the former to frictional properties of skin. mu and SSL were not statistically different between age groups on all regions except for the ankle, where lipid content was lower in the elderly. Similarly, mu did not vary between sex groups. Skin surface lipid content was statistically lower on the forehead, dorsal forearm and postauricular area in females. Both parameters, however, showed considerable regional variability. A significant linear correlation was established between mu and SSL combining all regions from all volunteers. When mu was plotted against SSL among individual anatomic sites, only the forehead and postauricular area showed significant linear correlations between the two parameters. These data suggest that surface lipid content plays a limited role in frictional properties of skin.

Increased stratum corneum turnover induced by subclinical irritant dermatitis

The chronic effects of the irritant sodium lauryl sulphate (SLS) on stratum corneum (SC) barrier function, determined by transepidermal water loss (TEWL) measurements and on epidermal cell kinetics, estimated by stratum corneum turnover time (SCTT) determination (dansyl chloride staining method), were investigated in 18 healthy female volunteers. SLS (7·5%) was applied without occlusion for 20 min once daily, over a period of 3 weeks (5 days a week) on dansyl chloride‐stained skin and on untreated skin. SCTT of untreated skin (19·3 ± 0·8 days; mean ± SEM) was not changed by daily treatment with water (control) (19·3±2.0) but was significantly reduced by SLS (10·9±0·6; P0·0001; compared to controls). However, TEWL was increased in SLS‐treated sites 1·5‐fold after 4 days of treatment (5·3±0·6 vs. 3·5 ± 0·3; P<0·001). At the end of the second week, TEWL was increased 2.6‐fold and after 3 weeks TEWL was 3·3 times higher than in controls (13·0±1·6 vs. 3·9, P0.0001) The intensity of SLS‐induced irritation as measured by TEWL was significantly correlated with baseline TEWL (r=0·50; P0·02) and significantly negatively correlated with SCTT of SLS treated sites (r=− 50; P0·02) but not with SCTT of untreated skin (r=0·19).

Partitioning of Chemicals into Human Stratum Corneum: Implications for Risk Assessment following Dermal Exposure

Assessment of the health hazard associated with chemical contamination of the skin is a complex problem of occupational and environmental relevance. A particularly important question is to what extent can the skin permeability of a given compound be predicted from simple experiments. The literature on percutaneous absorption identifies two key observations: (i) the stratum corneum (SC), the skins outermost layer, is the major barrier to chemical transport, and (ii) there are qualitative correlations between penetrant permeability and various oil/water partition coefficients (PCs). To obtain more quantitative predictions of permeation, we have evaluated SC/water and SC/isopropyl myristate (IPM, a model lipophilic vehicle) PCs of (a) para-substituted phenols of diverse physicochemical properties (4-acetamido-, 4-cyano-, 4-iodo-, and 4-pentyloxyphenol), (b) polychlorinated biphenyls (54%), and (c) 1,1,1,-trichloro-2,2-bis(p-chlorophenyl)ethane. Partition coefficients were determined as a function of the following variables: length of equilibration, initial drug concentration in the vehicle, SC delipidization, and SC source and preparation technique. The data demonstrate that reproducible partitioning can be obtained using the biological tissue of greatest relevance, and that the pattern of behavior observed, for the two different vehicles studied, is compatible with physicochemical expectations. We suggest that the PC values measured may be useful predictors of in vitro and in vivo skin transport and valuable assets, therefore, in the evaluation of risk following dermal exposure.

Susceptibility to irritant dermatitis induced by sodium lauryl sulfate

Because irritation changes skin physiology in many ways, we evaluated wether certain biophysical aspects of apparently healthy skin related to the vulnerability of skin to the model irritant sodium lauryl sulfate .

In Vivo Skin Penetration of Acitretin in Volunteers Using Three Sampling Techniques

Etretinate and acitretin are given orally to treat psoriasis and various keratinization disorders. Acitretin, the main active metabolite of etretinate, has the pharmacokinetic advantage of being rapidly eliminated, but it shares etretinates toxicologic profile. Thus a topical delivery of acitretin with no or reduced systemic adverse effects is desirable. To characterize the therapeutic potential of topically delivered acitretin, we quantitatively assessed its percutaneous penetration in healthy human volunteers. Additionally, three skin sampling techniques, the punch biopsy, the shave biopsy, and the suction blister technique, were validated to quantitate acitretin in the skin. The results suggest that topical delivery of acitretin renders skin concentrations which exceed those reported after oral administration of etretinate or acitretin. However, because of possible interlaminate drug contamination, drug localization within a particular skin compartment cannot be determined.