Development of an in vitro model to study compromised skin: pigskin versus the Phospholipid Vesicle-based Permeation Assay

Abstract

When the skin barrier is reduced, penetration of topical and transdermal drugs could potentially be enhanced and the risk of systemic effects is increased. The studies analysing penetration through intact or diseased skin are often limited by the variability in obtaining specimens of representative skin. The phospholipid vesicle-based permeation assay is an artificial barrier mimicking human stratum corneum and can be used to determine the permeability of drugs through the skin. The model is highly reproducible. In this study we aimed to further develop this model to represent the compromised human skin by inducing the changes in its preparation process. To evaluate the applicability of the model, the results must be compared to penetration data found in in vivo or ex vivo studies. For this purpose, we used pig skin, both intact and with induced damage in the barrier properties. The study was performed on the Franz diffusion cell systems by following the amount of the penetrated drug. The comparison of the permeability through the artificial barriers and pig skin was evaluated by using the model drug, diclofenac sodium. The results from the in vitro experiments showed that it is rather difficult to induce damage in the skin batter properties when using the pig skin. None of the treatments applied to damage the skin or enhance the penetration of drug as compared to intact skin, but an interesting finding was the extremely low penetration through the acid-damaged skin. However, we managed to increase the permeability of diclofenac sodium through the phospholipid vesicle-based permeation assay. The findings confirmed that, in order to follow the penetration of topically applied drugs through the damaged skin, a more reliable method to use is the non-animal skin-based models.

Key words: compromised skin; phospholipid vesicle-based permeation assay; pigskin