Comparison of in vivo and in vitro methods for the evaluation of barrier creams efficacy

Barrier creams have been used to protect the skin from exposure to chemicals and irritants. In most cases, they act by forming a superficial film allowing a mechanical protection of the skin. The evaluation of the efficacy of barrier creams is an argument in discussion at regulatory level. Efficacy tests were already proposed, either with non-toxic chemicals on human volunteers or with in vitro and animal models. The in vivo evaluation show high variability and appears not suitable for the screening of a large number of products and ethical reasons do not allow testing irritants or hazardous substances. Some attempts to propose in vitro methods were done in the past; they were based on the use of the Franz diffusion cells. Nevertheless, until now a validate, easy to use and reliable experimental model lacks and there are any officially recognized in vivo or in vitro methods to quantify the efficacy of barrier creams. In this study, an in vivo method based on the measurement of the transepidermal water loss (TEWL) and two in vitro methods based on Franz diffusion cell method and human epidermis as a membrane or on a 3D reconstructed human epidermis model were compared to evaluate barrier cream properties. TEWL is measured using an evaporimeter (Tewameter TM 210\uae, Courage-khazaka electronic), according to the guidelines of the Standardization group of the European Society of Contact Dermatitis. For in vitro methods, 1% caffeine in solution was used as hydrophilic chemical probe. Caffeine permeation profile is well known and it is considered a chemical reference in the OECD 428 and related Guidance Document for the conduct of skin absorption studies. Experiments were performed over a period of three hours. Petrolatum (WP) was used as positive control, being overall considered efficient against hydrophilic molecule. Six skin protective products on the market, O/W or W/O creams, were tested. Each product was spread on the membranes at realistic usage dose and left to room temperature two hours before application of caffeine solution. TEWL results were quite variable and the method required specific ambient conditions other than being time consuming. As far as the in vitro method is concerned, the permeated amount of caffeine through tissues (control solution) were considered as reference for evaluating the protective effect of each product. In the case of application of WP, the permeation of caffeine resulted not more than 2% by using both methods. By using the tested barrier creams, a quite variable reduction of caffeine permeation was observed. With respect to control solution, Franz cell method and 3D reconstructed human epidermis model showed a caffeine permeation range from 10 to about 85%. The results obtained by using the two methods were in agreement, suggesting that both in vitro methods were able to discriminate among different cream barrier products. Moreover, a threshold value indicating the protective effect should be established within the obtained range