Alteration of the Structure of Human Stratum Corneum Facilitates Transdermal Delivery

Anne Mundstock,Marek Haftek,Fabrice Pirot,Rawad Abdayem

doi:10.2174/1874372201408010072

Abstract

Transdermal transport of pharmacologically active components into the skin depends on the ability of galenic formulations to overcome the stratum corneum (SC) barrier. Microemulsions (ME) are thermodynamically stable liquid systems composed of water, oil and surfactants which may be used for skin permeation and enhance penetration of hydrophobic as well as hydrophilic compounds. We investigated using transmission electron microscopy the effect of ME on human epidermis ex vivo, in order to establish relationship between the type of ME, i.e.: oil-in-water, water-in-oil, gellike, thickened or not with colloidal silica, and the ultrastructural changes in SC barrier resulting from their topical application. ME induced various degrees of dissociation of the SC. The intercellular lipid matrix in the SC became disorganized, which contributed to the separation of corneocytes. This effect was intensified with the increasing oil content in the ME and also when ME were applied under occlusion. The observed morphological changes were in agreement with the increased permeability of ME-treated skin to both lipophilic and hydrophilic compounds reported in the literature. Severe deterioration of the SC barrier induced with the selected ME makes them suitable for selected indications only.

Highlights

Skin is a very effective barrier which protects the human body from environmental influences such as ultraviolet radiation, chemicals and pathogenic microorganisms
Isopropyl myristate and surfactant – cosurfactant mix used in our study, which segregate to the lipophilic compartment, could be predicted to disturb the intercellular lamellar lipids in a dose-dependent manner
Ruthenium tetroxide staining, which enabled us to observe the organization of the lipid lamellae in the spaces between the corneocytes, confirmed that the most profound changes in this compartment occurred after incubation with the w/O ME

Summary

Introduction

Skin is a very effective barrier which protects the human body from environmental influences such as ultraviolet radiation, chemicals and pathogenic microorganisms. It forms a barrier against the loss of water and electrolytes [1]. The whole SC in human ventral skin consists of around 15-20 cell layers, but these numbers do vary according to the anatomical localization. They are significantly lower on the eyelids and markedly higher on the palms and soles. The extracellular spaces are filled with lamellar sheets of lipids, primarily cholesterol, free fatty acids and ceramides in roughly equimolar proportions [1]

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Results

Conclusion