Ann Dermatol.  2013 Feb;25(1):5-11. 10.5021/ad.2013.25.1.5.

Preventive Effects of Multi-Lamellar Emulsion on Low Potency Topical Steroid Induced Local Adverse Effect

• Sul GD
• Park HJ
• Bae JH
• Hong KD
• Park BD
• Chun J
• Jeong SK
• Lee SH
• Ahn SK
• Kim HJ

• KMID: 2265964
• DOI: http://doi.org/10.5021/ad.2013.25.1.5

Abstract

BACKGROUND
Topical steroid treatment induces diverse local Wand systemic adverse effects. Several approaches have been tried to reduce the steroid-induced adverse effects. Simultaneous application of physiological lipid mixture is also suggested.
OBJECTIVE
Novel vehicles for topical glucocorticoids formulation were evaluated for the efficacy of reducing side-effects and the drug delivery properties of desonide, a low potency topical steroid.
METHODS
Transcutaneous permeation and skin residual amount of desonide were measured using Franz diffusion cells. The in vivo anti-inflammatory activity was evaluated using murine model.
RESULTS
Topical steroids formulation containing desonide, in either cream or lotion form, were prepared using multi-lamellar emulsion (MLE), and conventional desonide formulations were employed for comparison. MLE formulations did not affect the anti-inflammatory activity of the desonide in phobol ester-induced skin inflammation model, compared with conventional formulations. While the penetrated amounts of desonide were similar for all the tested formulations at 24 hours after application, the increased lag time was observed for the MLE formulations. Interestingly, residual amount of desonide in epidermis was significantly higher in lotion type MLE formulation. Steroid-induced adverse effects, including permeability barrier function impairment, were partially prevented by MLE formulation.
CONCLUSION
Topical desonide formulation using MLE as a vehicle showed a better drug delivery with increased epidermal retention. MLE also partially prevented the steroid-induced side effects, such as skin barrier impairment.

Keyword

Epidermal permeability barrier function; Multilamellar emulsion; Skin permeation; Topical glucocorticoids

MeSH Terms

Desonide
Diffusion
Epidermis
Glucocorticoids
Inflammation
Permeability
Retention (Psychology)
Skin
Steroids
Desonide
Glucocorticoids
Steroids

Figure

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  Fig. 1 Anti-inflammatory activity of tested formulations in phobol ester-induced skin inflammation. (A) Significant increase of skin thickness was observed after chronic TPA application, which was normalized after 3-days application of desonide formulations. (B, C) Increased epidermal mRNA expressions for proinflammatory cytokine, IL-1β and TNF-α, were also observed in inflamed skin, and topical application of desonide resulted in a reduction of both cytokines. Data represents arithmetic means±standard deviation (SD), and p-value less than 0.05 was considered as statistically significant (*p<0.05, ***p<0.001). TPA: 12-O-tetradecanoylphorbol-13-acetate, MLE: multi-lamellar emulsion, IL: interleukin, TNF: tumor necrosis factor.

• 

  Fig. 2 Multi-lamellar emulsion (MLE) significantly reduced steroid-induced impairment of epidermal permeability barrier function induced by topical glucocorticoid treatment. (A) While the similar skin atrophy was observed in all the tested formulations, (B) increase of trans-epidermal water loss (TEWL) was significant in only the commercial desonide products treated site but not in MLE based desonide products treated site. Data represents arithmetic means±standard deviation (SD), and p-value less than 0.05 was considered as statistically significant (**p<0.01).

• 

  Fig. 3 Transcutaneous penetration and epidermal accumulation of desonide in vitro. (A) Cumulative amount of desonide permeated through excised skin was measured at indicated times, and (B) amount of desonide accumulated in the epidermis and dermis at 6 hours after application was measured. Values represent the arithmetic means±standard deviation (SD) (triplicate) in penetration measurement. MLE: multi-lamellar emulsion.

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