Measurement of sodium lauryl sulfate-induced skin irritation.

Besides visual evaluation, skin irritation induced by sodium lauryl sulfate (SLS) may be characterized by bioengineering measurements, such as skin colour reflectance, transepidermal water loss (TEWL) or hydration. Short application times or low concentrations of the irritant usually do not modify the visual aspect of the skin, and the measurements described above are unchanged or only slightly altered. We were looking for a suitable method to measure cutaneous changes not detectable by usual bioengineering procedures. Therefore these measurements were compared to those of dynamic function testing of the stratum corneum, namely sorption-desorption and moisture accumulation tests. Different concentrations of SLS (0.1%, 0.5%, 2.5%), application times (15 min, 24 h) and times of testing (1 h, 24 h after patch removal) were investigated on the ventral forearm of human subjects. When SLS was applied for a short period (15 min), 1 h after patch removal skin colour, TEWL and hydration were not modified, while increases in hygroscopicity, water-holding capacity and water accumulation were detected depending on the applied concentration. Increase of hygroscopicity was closely correlated with the alteration of epidermal barrier function (TEWL). We demonstrated that sorption-desorption and moisture accumulation tests performed on SLS-treated areas for a short period, without visible modifications, could evaluate changes of the stratum corneum properties. We consider these tests as useful complementary methods to skin colour, TEWL and hydration measurements, particularly in the detection of subclinical skin injuries.

Skin penetration and sun protection factor of ultra-violet filters from two vehicles.

PURPOSE: In order to improve our knowledge on the efficacy and safety of sunscreen products, we measured the skin penetration profiles of ultra-violet (UV) filters in vitro and in vivo, and the corresponding sun protection factors (SPF) from two vehicles (an O/W emulsion-gel and petroleum jelly). METHODS: The UV filters tested were oxybenzone (5%, A), 2-ethylhexyl 4-methoxycinnamate (7.5%,B), and 2-ethylhexylsalicylate (3%,C). Two mg/cm(2) were applied for 2 min to 6 h. In vitro penetration measurements were performed with static diffusion cells. In vivo, horny layer concentrations were measured after stripping and the SPF evaluated as recommended by the COLIPA-guidelines. RESULTS: Significant differences between vehicles were noticed in vitro as well as in vivo. In vitro, the emulsion-gel generated higher epidermal concentrations than petroleum jelly. Values at 6 h, expressed as percent of the applied dose for A, B, and C were 4, 9, and 7% for the emulsion-gel and 2, 1, and 2% for petroleum jelly. An opposite trend was noticed, mainly for A, in the deeper skin layers with concentrations of 2% in the dermis and 5% in the receptor fluid for petroleum jelly and 0.6% and 1% for the emulsion-gel respectively. In vivo, for each UV filter, maximal stratum corneum levels (15 strips) were obtained at 0.5 h with percentages of the applied doses of 50% for the emulsion-gel and 15 percent for petroleum jelly. SPFs, measured 0.5 h after application amounted to 14 for the emulsion-gel and 5 for petroleum jelly, and decreased in both cases by a factor 2.2 after removal of non penetrated product. CONCLUSIONS: These preliminary results demonstrated that UV filters penetration and retention as well as expected SPF could be optimized by a suitable vehicle.

Emollients and photo(chemo)therapy: a call for caution.

BACKGROUND: Emollients used for skin care, treatment of a disease or lubrication, before irradiation during the course of phototherapy or photochemotherapy, may significantly interfere with the transmission of UV light and may influence the outcome of the therapy. OBJECTIVE: These experiments should characterize and quantify the possible interactions of usual emollients with UV light transmission. METHOD: The method was an in vitro technique similar to the one already used for the determination of sun protection factors of topical sunscreen preparations. RESULTS: Among the products tested, two showed a significant photoprotection capable of interfering with the course of therapy. Oils enhanced UV light transmission significantly. CONCLUSIONS: Emollients may show significant interference with UV light transmission during phototherapy or photochemotherapy. The outcome and course of the therapy could thus be significantly modified.

Barrier function of the skin in a repetitive irritation model and influence of 2 different treatments.

BACKGROUND/AIMS: The aim of this study was to develop and characterize an experimental model of cumulative irritant contact dermatitis using the repetitive application over 2 weeks of 2 different irritative stimuli, sodium lauryl sulphate (SLS) in low concentration and toluene. Further, it was intended to look at the effect of 2 different treatments which could influence the regeneration of the skin barrier, as already investigated in preliminary short-term experiments. METHODS: Occlusive short-time daily application of the irritants (SLS 30 min; toluene 10 min) was performed. After removal of the occlusive patch, the irritated areas were treated with 2 different preparations, Lotio Alba Aquosa and vaseline (white petroleum jelly). Bioengineering techniques were used to precisely measure the skin condition. RESULTS: A mild irritation was obtained under these experimental conditions. The bioengineering measurements allowed us to differentiate both irritants through their different influences on trans-epidermal water loss and skin hydration. Treatment with vaseline did not significantly influence the course of the irritation, but Lotio Alba Aquosa clearly potentiated it, whereby different effects were noticed for both irritative stimuli. CONCLUSIONS: The use of bioengineering techniques in this model of mild cumulative irritation allowed us to differentiate the action of both irritants, showing that they act through different mechanisms. The results of the treatments pointed out the need to treat an irritation with the right product for the right time period.

Bioengineering measurements of barrier creams efficacy against toluene and NaOH in an in vivo single irritation test.

BACKGROUND/AIMS: By now, only a few models have been published with the goal of testing barrier creams in vivo in humans. The aim of this study was to evaluate with a single irritation test, barriers creams in humans against a lipophilic and a hydrophilic irritant, toluene and NaOH, respectively. METHODS: Both irritants were applied for 15 min after pretreatment of the skin with barrier creams. Non-invasive bioengineering methods, such as skin colorimetry (a*) and cutaneous blood flow (CBF) measurements were used to assess product protection. RESULTS: After toluene application on control sites, the irritation appeared quickly (Tmax =3 min after patch removal), was significant (+5-6 units for a* and+80% for CBF) and did not return to base value within 1 h. Skin irritation after NaOH application, as measured by a*, was less important (+2 units) and occurred later (T"max=40 min after patch removal). For this irritant, CBF response was minor and variable. When testing barrier properties of the products, none of them were able to prevent the skin erythema induced by toluene. Against NaOH, one barrier cream as well as petrolatum and a fatty cream protected the skin significantly. CONCLUSION: The present study points out the unsatisfactory effectiveness of several commercially available barrier creams claimed to protect against lipophilic or hydrophilic irritants.

Stratum corneum dynamic function measurements after moisturizer or irritant application.

Two simple tests were conducted which allowed the quantification of parameters that characterize the stratum corneum (SC) dynamic functions in vivo under physiological conditions after moisturizer applications for 1 h and after irritation with different concentrations of sodium lauryl sulphate (SLS; 0.5-4%) applied under occlusion for 15 min or 24 h. Both tests, the sorption-desorption test (SDT) and the moisture accumulation test (MAT), were performed with a Nova Dermal Phase Meter 9003. The following parameters were quantified: prehydration state (SDT, MAT), hygroscopicity, water-holding capacity (SDT), water accumulation velocity and water accumulation (MAT). These procedures allowed the demonstration of the water-holding effect of urea contained in moisturizers. Differences between the long and the short application time of SLS were characterized by differences in SC dynamic functions while the hydration state was not changed. An effect on transepidermal water loss (TEWL) was noted only after the long application time, although the MAT clearly showed dynamic parameters to be changed after 15 min of treatment. These tests were simple in practice and allowed the demonstration of functional modifications of the SC while other parameters remained unchanged. They gave insight into possible action mechanisms of urea and SLS in the SC.

Hydration, transepidermal water loss, pH and skin surface parameters: correlations and variations between dominant and non-dominant forearms.

The aim of this study was to examine differences between the skin of both forearms with regard to several parameters: hydration (skin capacitance), transepidermal water loss (TEWL), pH and skin surface parameters. Possible correlations between measurements were investigated. Thirty-three healthy women (32.6 +/- 8.4 years) participated in the study. The different parameters were measured on each volar forearm (dominant and non-dominant) at precisely delineated sites. TEWL and developed length (DL) were significantly increased on the dominant forearm (P < 0.001 and P < 0.01, respectively). In addition, a correlation matrix was calculated with the differences between dominant and non-dominant forearms for all the parameters measured. Only the skin surface parameters were found to be interrelated with this statistical approach. These data confirm that randomization between forearms is essential in the design of a reliable experimental plan, and indicate the lack of relationship between these measurements as assessed in a group of healthy young women.

Evaluation of barrier creams: an in vitro technique on human skin.

A method was developed to measure in vitro on human skin the effectiveness of barrier creams against three dyes (eosin, methyl-violet and oil red O) with different n-octanol/water partition coefficients (0.19, 29.8 and 165, respectively). Some galenic properties (water washability, water content and viscosity) of the products were also evaluated to try to understand the mechanisms of such a protection. The barrier creams were assayed by measurements of the dyes in the epidermis of protected skin samples after an application time of 30 min. Whereas some products showed some degree of protection, as claimed on the packaging, we demonstrated in several cases disagreement with the manufacturer's information. Surprisingly, petrolatum was found to provide the best protection of all tested products in our in vitro model. There was no correlation between the galenic parameters of the assayed products and the level of protections, indicating that neither the water content nor the consistence of the formulations influenced the protection effectiveness. In conclusion, regarding the possible skin effects of some irritants, our results stress that barrier creams should be used with caution, knowing the protection limits of some of the formulations marketed.

Surface recovery and stripping methods to quantify percutaneous absorption of caffeine in humans.

The percutaneous absorption of caffeine from two vehicles, an emulsion and an acetone solution, was quantified by in vivo techniques in humans. A surface recovery technique over a 6-h application and a stripping method after a 30-min application were performed on the volar aspect of the forearm on 12 volunteers. Caffeine was assessed by HPLC. Two phases were distinguished in the percutaneous absorption of caffeine: a higher filling up of the stratum corneum with the oil-in-water emulsion than with the acetone solution, which was then followed by a steady-state flux corresponding to the penetration in the living tissues. The permeability constants (Kp) with emulsion and acetone were 1.59 x 10(-4) and 9.53 x 10(-8) cm/h, respectively. The stripping method showed concentrations of caffeine in stratum corneum that were five times higher with emulsion (212 ng/cm2) than with acetone (37 ng/cm2). With acetone as a vehicle, approximately 40% of caffeine of the cornfield layer was found around the treated area. This sizeable lateral spread within the stratum corneum was not observed with the emulsion.

Ibuprofen epidermal levels after topical application in vitro: effect of formulation, application time, dose variation and occlusion.

The influence of vehicle (two oil-in-water emulsions and two gels, each containing 10% or 5% ibuprofen) application time (0.5, 1, 2 h), applied dose (1.5, 3, 6, 12 mg/cm2), time (24 h after an 0.5 h application time), and occlusion on the epidermal concentration of ibuprofen was investigated. The drug concentration in the epidermis was measured by HPLC. All results were expressed as microgram drug/mg epidermal protein. The application time had no influence on the epidermal drug concentration, whereas the two gel formulations produced concentrations approximately twice those obtained with the emulsions. A significant positive correlation was found between the applied dose and the epidermal concentration for each formulation. After 24 h the amount of drug remaining in the epidermis was low (reduced by factors of 10-20). Occlusion produced higher concentrations, but only with the 2-h application time. The methods are reliable, and useful in ranking vehicles according to their ability to release ibuprofen into the epidermis. Future investigations should explore the relationship between epidermal concentration and anti-inflammatory efficacy in vivo.

Effect of pressure on in vitro percutaneous absorption of caffeine.

The effect of increased pressure, which is a mechanical property of massage, was investigated on the percutaneous absorption of an amphiphilic compound (caffeine) in vitro on Franz diffusion cells, using excised human skin. 50 microliters of either a 320 micrograms/ml or a 15 mg/ml acetone solution of caffeine were pipetted onto the surface of each skin sample, which represented caffeine skin deposits of 5 micrograms/cm2 and 240 micrograms/cm2 respectively. During each experiment, a pressure device delivering 0.25 bar over the atmospheric pressure was applied for the first 30 min on half of the cells. At 2, 4, 6, 8, 12 and 24 h the aqueous dermal bathing solution, containing 14 g/l albumin, was removed and chromatographed. With the applied dose of 5 micrograms/cm2 no statistical difference was found between the cumulated absorbed amount under atmospheric pressure and increased pressure. On the other hand, with the applied dose of 240 micrograms/cm2, the permeation of caffeine was 1.8 times higher under increased pressure than the permeation under atmospheric pressure (p < 0.05). This enhancing effect of increased pressure was probably connected to either an improved transappendageal route during the percutaneous absorption process or a higher stratum corneum filling-up.

Feasibility of measuring the bioavailability of topical ibuprofen in commercial formulations using drug content in epidermis and a methyl nicotinate skin inflammation assay.

A method has been developed which simultaneously compares the inhibition of an inflammation induced by a methyl nicotinate assay with the concentration of drug in the human epidermis determined in vitro following topical application of two 10% ibuprofen formulations. The bioavailability of drug from commercial gel and emulsion was assessed after the application of various doses (3, 6 and 12 mg/cm2) and an application time of 0.5 h at two time points: 0.5 and 24 h (only with the 12 mg/cm2 dose) after the removal of the non-steroidal anti-inflammatory drug (NSAID) from the skin. In parallel, we assessed the epidermal concentration of the drug in vitro and evaluated the anti-inflammatory effect of the topicals in vivo. A correlation (r = 0.9603, p < 0.001) between the amount of drug in the epidermis expressed as micrograms per milligram of epidermal protein and the corresponding inhibition of the inflammation was observed. Increasing the amount of drug in the epidermis correlated with an increased inhibition of the inflammation. The gel formulation released more drug to the skin and produced a greater anti-inflammatory effect. Topical NSAID concentration in treated skin can therefore be determined and correlates well with the resulting pharmacodynamic activity. This approach will likely have utility in optimizing topical NSAIDs.

Effect of occlusion on in vitro percutaneous absorption of two compounds with different physicochemical properties.

It is a general rule that percutaneous absorption is increased when the site of application is occluded. In this study we compared the in vitro permeation profiles of two molecules with different physicochemical properties under occluded versus unoccluded conditions. Human abdominal skin samples were mounted on Dianorm Teflon macro 1 cells and Franz diffusion cells which represented occluded or unoccluded conditions, respectively. Our data show that occlusion increased the permeation of citropten (lipophilic compound) 1.6 times whereas that of caffeine (amphiphilic compound) remained unchanged. This lack of penetration enhancement under occluded conditions has also been observed by other authors, especially concerning hydrophilic and slightly lipophilic molecules. Our results support the view that occlusion does not necessarily increase the percutaneous absorption of a chemical.

Transepidermal water loss related to volar forearm sites in humans.

The aim of this study was to demonstrate differences in human skin transepidermal water loss (TEWL) in vivo related to site on volar forearm. Fourteen healthy volunteers entered the study and seven sites were tested. After randomization of both forearm and measure order, TEWL measurements were performed using the Servo Med Evaporimeter. TEWL values next to the wrist were found statistically greater than on the other sites. Hence wrist region should preferably be excluded from TEWL measurements on forearm.

A new micronized 5-methoxypsoralen preparation. Higher bioavailability and lower UVA dose requirement.

A new tablet of micronized 5-methoxypsoralen (5-MOP) and a commonly used tablet in therapy (Psoraderm 5) were compared in 12 healthy subjects. Each subject ingested 1.2 mg/kg body weight of each formulation on different days. Bioavailability and phototoxicity of 5-MOP were compared. The results showed that serum and suction blister concentrations were significantly higher and occurred earlier after the oral intake of the micronized preparation. A series of graduated UVA doses were administered, one dose each time the concentration serum peaked, in order to determine the minimum phototoxic dose for each formulation. The micronized preparation induced greater photosensitivity than the unmicronized one. The micronized 5-MOP tablet may thus allow lower doses of UVA to achieve therapeutic results in photochemotherapy and a shortened waiting period following ingestion of drug.

The tetracyclines in dermatology.

Tetracycline is one of the most widely used antibiotics. It may share some properties with conventional immunosuppressive drugs and act as an anti-inflammatory agent in the treatment of inflammatory disease. This article reviews cutaneous diseases that have been treated with tetracyclines and their antiinflammatory and immunosuppressive properties.

Intestinal permeability in patients with psoriasis.

A possible relationship between intestinal structure and function in the pathogenesis of psoriasis has recently brought about considerable interest. The purpose of this study was to evaluate the intestinal permeability in psoriatic patients by comparing it with healthy controls. 15 psoriatic patients and 15 healthy volunteers entered the study. Intestinal permeability was evaluated using the 51Cr-labeled EDTA absorption test. The 24-h urine excretion of 51Cr-EDTA from psoriatic patients was 2.46 +/- 0.81%. These results differed significantly from controls (1.95 +/- 0.36%; P less than 0.05). The difference in intestinal permeability between psoriatic patients and controls could be due to alterations in the small intestinal epithelium of psoriatics.

High-performance liquid chromatographic determination of citropten and bergapten in suction blister fluid after solar product application in humans.

Citropten (5,7-dimethoxycoumarin) and bergapten (5-methoxypsoralen) are present in bergamot oil which is used as a tanning cosmetic product. The aim of this study was to quantify, using high-performance liquid chromatography, the amount of citropten and bergapten in the skin after suntan products application (an emulsion and an oil formulation). A suction blister technique performed of the anterior aspect of the forearm permitted the collection of these two accumulated molecules. Fluorometric and ultraviolet detections were used for citropten and bergapten determinations, respectively.