Allergy Asthma Immunol Res.  2011 Apr;3(2):96-102. 10.4168/aair.2011.3.2.96.

Pseudoceramide-Containing Physiological Lipid Mixture Reduces Adverse Effects of Topical Steroids

• Kim HJ
• Park HJ
• Yun JN
• Jeong SK
• Ahn SK
• Lee SH

• KMID: 2130360
• DOI: http://doi.org/10.4168/aair.2011.3.2.96

Abstract

PURPOSE
Various therapeutic approaches have been suggested for preventing or reducing the adverse effects of topical glucocorticoids, including skin barrier impairment. Previously, we have shown that impairment of skin barrier function by the highest potency topical glucocorticoid, clobetasol 17-propinate (CP), can be partially prevented by co-application of a physiological lipid mixture containing pseudoceramide, free fatty acids, and cholesterol (multi-lamellar emulsion [MLE]). Skin atrophic effects of CP were also partially reduced by MLE. In this study, the preventive effects of MLE on the lowest potency topical glucocorticoid, hydrocortisone (HC), were investigated using animal models.
METHODS
Anti-inflammatory activity of topical HC was evaluated using a 12-O-tetradecanoylphobol-13-acetate-induced skin edema model. Topical steroid induced adverse effects were evaluated using hairless mouse.
RESULTS
The results showed that the anti-inflammatory activity was not altered by co-application of either MLE or hydrobase. However, co-application of MLE and 1.0% HC showed less impairment in the epidermal permeability barrier function, skin hydration, and skin surface pH compared with hydrobase. Stratum corneum integrity, evaluated by measuring trans-epidermal water loss after repeated tape stripping, showed less damage with MLE co-application. Long-term application of topical HC induced skin atrophy, measured by a reduction in skinfold and epidermal thickness and in the number of epidermal proliferating cell nucleus antigen (PCNA)-positive keratinocytes. Co-application of MLE did not affect the skinfold or epidermal thickness, but the number of PCNA-positive keratinocytes was less decreased with MLE use.
CONCLUSIONS
These results suggest that co-application of MLE is effective in reducing the local adverse effects of low-potency topical glucocorticoids and supports the therapeutic efficacy of physiological lipid mixtures on skin barrier function.

Keyword

Epidermal permeability barrier function; multilamellar emulsion; topical glucocorticoids

MeSH Terms

Animals
Atrophy
Cell Nucleus
Cholesterol
Clobetasol
Edema
Fatty Acids, Nonesterified
Glucocorticoids
Hydrocortisone
Hydrogen-Ion Concentration
Keratinocytes
Permeability
Skin
Steroids
Water Loss, Insensible
Cholesterol
Clobetasol
Fatty Acids, Nonesterified
Glucocorticoids
Hydrocortisone
Steroids
Water Loss, Insensible

Figure

• 

  Fig. 1 Anti-inflammatory activity of topical hydrocortisone (HC) with multi-lamellar emulsion (MLE) and hydrobase. Co-application of either MLE or hydrobase did not inhibit ear weight increase by TPA application, compared with HC only treatment. MLE or hydrobase was applied 10 min after TPA application. After 6 hr, ear skin was taken with a 6-mm punch, tissue weight was measured, and inhibitory activity was calculated.

• 

  Fig. 2 Change of skin functions during topical steroid treatment. Topical hydrocortisone treatment-induced skin barrier impairments, represented by an increase in trans-epidermal water loss (A), reduction of skin hydration (B), and increase in skin surface pH (C). After discontinuation of steroid treatment, restoration of skin hydration and skin surface pH were observed after 3 days. Co-application of pseudoceramide-containing multi-lamellar emulsion showed less impairment in all the measured parameters compared with hydrobase.

• 

  Fig. 3 Skin barrier integrity assessed by change of trans-epidermal water loss (TEWL) after tape stripping. After 10 strips, TEWL was significantly higher in the hydrobase co-applied site compared with the multi-lamellar emulsion (MLE) co-applied site.

• 

  Fig. 4 Skin atrophic effects of topical hydrocortisone. During topical treatment, skinfold thickness was measured (A), and after 6 days of steroid treatment, skin biopsy was taken and histological analysis performed. Reduction of epidermal thickness was observed in both groups (normal epidermal thickness represented by dotted line) (B) the multi-lamellar emulsion co-applied site (C) showed less reduction in epidermal thickness compared with hydrobase (D).

• 

  Fig. 5 Reduction of epidermal proliferation by topical hydrocortisone (HC) treatment. proliferating cell nucleus antigen (PCNA) staining on skin biopsy samples showed a decrease in the number of PCNA-positive keratinocytes in the basal layer after 6 days of HC treatment compared with that in normal skin (represented by dotted line) (A). Multi-lamellar emulsion (MLE) co-application partially prevented the reduction of PCNA-positive keratinocytes (B) compared with hydrobase (C).

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