Limitations of pig skin as in vitro model mimicking skin with damaged barrier properties

Abstract

Skin is an alternative route for the administration of drugs and has several advantages compared to the oral administration route. However, for a drug substance to act systemically after topical application it has to penetrate through the skin barrier (stratum corneum). Therefore it is important to investigate drug penetration through both healthy and damaged skin (reduced barrier properties). In this study Franz diffusion cells was used to determine the extent to which chloramphenicol penetrated through intact and treated (different degree of induced damage) pig ear skin. The skin slices were treated with tape-stripping and treatment with strong alkali, heat, and burning of the skin, respectively. The results were not as expected; the cumulative penetration of chloramphenicol through the treated skin did not increased as compared to intact skin, except for the treatment with the strong alkali for five minutes. This treatment resulted in a modest enhanced penetration. However, the phospholipid vesicle-based permeation assay has been developed to mimic skin. This barrier is made on a filter support where small liposomes are fitted in the pores of the filter and large liposomes are deposited on the top. The stability of the PVPA barrier was tested over a period of 4 week and the results indicated that the integrity of the barriers were not influenced after storage at – 75 ˚C for 21 days. In order to mimic the compromised skin, we attempted to induce leakiness of different degree to the PVPA barrier by changing the ethanol concentration in the liposome suspension. Although the results from the permeability experiments showed no significant differences between the barriers with various ethanol concentrations, it seems that the original PVPA model can be modified to mimic the compromised skin. Comparing the in vitro model based on the damaged pig skin to the model based on the PVPA barrier, it seems that PVPA model provides more reliable and reproducible model.