Comparison of Cutaneous Bioavailability of Cosmetic Preparations Containing Caffeine or α-Tocopherol Applied on Human Skin Models or Human Skin ex vivo at Finite Doses

Abstract

The use of human skin models for performing cutaneous bioavailability studies has been little investigated. For instance, only few studies have been reported on human skin models dealing with vehicle effects on percutaneous penetration. The present study aimed at evaluating the influence on caffeine’s and α-tocopherol’s cutaneous bioavailability of cosmetic vehicles such as a water-in-oil emulsion, an oil-in-water emulsion, a liposome dispersion and a hydrogel applied at finite dose using the reconstructed human skin models EpiDerm^® and Episkin^®. The results were compared with those obtained in human skin ex vivo using similar experimental conditions. It was demonstrated that the rank order of solute permeability could be correctly predicted when the preparation was applied at a finite dose in human skin models, at least when solutes with far different physicochemical properties such as caffeine and α-tocopherol were used. If only slight effects of cosmetic vehicle on skin bioavailability were observed in human skin ex vivo, they were less predictable using skin models. Especially, alcohol-containing vehicles seemed to behave differently in EpiDerm as well as in Episkin than on human skin ex vivo. Stratum corneum intercellular lipid composition and organization of human skin models differ to some extent from that of human stratum corneum ex vivo, which contributes to less pronounced barrier properties, together with the increased hydration of the outermost stratum corneum layers of the models. These features, as well as still unknown factors, may explain the differences observed in vehicle effects in human skin ex vivo versus human skin models.

Effects of Growth Conditions on the Barrier Properties of a Human Skin Equivalent

“…The need for a suitable model for permeability testing has necessitated the development and evaluation of several tissue-cultured in vitro skin models, frequently known as bioengineered skin substitutes or skin equivalents (SEs). Skin equivalents have been developed and researched over the past years for various applications, mainly as skin replacements in burns or wounds (3,4), for skin biology research (5), for cutaneous irritation and toxicity testing (6,7) and as models for permeability testing of agents and formulations (8,9). These skin substitutes are cultured in a controlled environment, thus increasing reproducibility and reducing scope for larger standard deviations normally encountered with human skin data.…”

Engineered Skin Tissue Equivalents for Product Evaluation and Therapeutic Applications

“…In permeation studies, it was found that the maximum transport rate was reached faster in the EpiDerm model when compared to native human skin; however, a prolonged application of hydrogel on the skin model leads to a decrease in permeation. Overall, the rank order of permeability was about the same between the model and the human skin . Another transport study, this time with the lipophilic drug flufenamic acid, demonstrated a higher permeation and transport rate in the model than in the native tissue…”

“…Another study found that the concentration of surfactants needed to trigger a reaction in the model was lower than that was needed in vivo . In permeability studies, caffeine permeation was monitored and found to exhibit the same behavior as the human skin …”

Influence of the application area on finite dose permeation in relation to drug type applied

“…Correlations between in vitro and in vivo experiments have been shown previously (1–4). Thus, for example, for bioequivalence studies, in vitro experiments are beneficial to determine the difference between two vehicles (5).…”