In Vitro Modeling of Skin Barrier Disruption and its Recovery by Ceramide-Based Formulations.

Disrupted skin barrier, one of the severe attributes of inflammatory skin diseases, is caused by lower content and pathological changes of lipids in the uppermost skin layer-stratum corneum (SC). Restoring skin barrier with native skin lipids, especially ceramides (Cers), appears to be a promising therapy with minimum side effects. For testing the efficiency of these formulations, suitable in vitro models of the skin with disrupted barriers are needed. For the similarity with the human tissue, our models were based on the pig ear skin. Three different ways of skin barrier disruption were tested and compared: tape stripping, lipid extraction with organic solvents, and barrier disruption by sodium lauryl sulfate. The level of barrier disruption was investigated by permeation studies, and parameters of each method were modified to reach significant changes between the non-disrupted skin and our model. Fourier transform infrared (FTIR) spectroscopy was employed to elucidate the changes of the skin permeability on the molecular scale. Further, the potential of the developed models to be restored by skin barrier repairing agents was evaluated by the same techniques. We observed a significant decrease in permeation characteristics through our in vitro models treated with the lipid mixtures compared to the untreated damaged skin, which implied that the skin barrier was substantially restored. Taken together, the results suggest that our in vitro models are suitable for the screening of potential barrier repairing agents.

Ceramide liposomes for skin barrier recovery: A novel formulation based on natural skin lipids.

Diseases related to a disrupted skin barrier are accompanied by lower levels of ceramides in the stratum corneum (SC) lipid matrix. Delivering ceramides directly into damaged skin is a viable alternative to conventional corticosteroids, but is hindered by their low skin bioavailability and limited nanoformulation ability. Here, we developed stable liposomal systems containing ceramides and other SC lipids, and tested their effectiveness in skin barrier repair. Lipid film hydration and high-pressure homogenization were used to prepare different types of liposomes. To determine the stability, the particle size and polydispersity index were measured. The optimal systems were found to include ceramide 3 and 6, cholesterol and stearic acid, with 10% urea in phosphate-buffered saline as the aqueous phase. The ability of the system to repair chemically-damaged porcine skin was tested. While treatment by a standard lipid suspension reduced the passage of a model permeant only to a limited extent, drug flux through the liposomally-treated skin was much closer to permeation through intact skin. The non-homogenized liposomes were more effective than their homogenized version. These findings were also confirmed by FTIR measurements. This suggests that our approach to liposomal development has considerable potential for the repair of a disrupted skin barrier.