Light and Electron Microscopic Findings in a Model of Human Cutaneous Candidosis Based on Reconstructed Human Epidermis Following the Topical Application of Different Econazole Formulations

Abstract

The effects of two commercially available econazole formulations (econazole nitrate cream, econazole liposome gel) on uninfected reconstructed human epidermis and on a model of human cutaneous candidosis were investigated. The morphological alterations of the reconstructed epidermis after infection and treatment were analysed with light and electron microscopy. The most important Candida albicans-specific alterations of the recently established in vitro model of human cutaneous candidosis were scaling, hyperkeratosis, parakeratosis, dyskeratosis and spongiosis. A single application of the cream to the uninfected reconstructed epidermis caused more epidermal barrier damage and irritative toxic effects than the liposome gel. Treatment of the modelled human cutaneous candidosis with the cream also resulted in increased toxic effects, e.g., enhancement of scaling with invasion of Candida albicans blastospores into the stratum corneum and intracellular vacuoles. After application of the liposomal preparation invasion of Candida albicans in the stratum corneum could not be detected and toxic effects were reduced. Some of the Candida albicans-specific alterations such as hyperkeratosis, focal thickening of the stratum corneum, dyskeratosis and parakeratosis were completely eliminated. The liposomal formulation increased slightly the morphological alterations of the blastospores. Remnants of the cream formulation could be detected only very rarely in the stratum corneum or the blastospores. The liposomal preparation showed a strong affinity for the Candida albicans cells and the stratum corneum. Intact liposomes could even be observed in the intercellular spaces of the upper stratum corneum. As successful treatment depends on the ability to target the liposomal agent to the wanted site of action, this might be useful for more effective treatment of cutaneous candidosis.