It is preferred that topically administered drugs act either dermally or transdermally. For that reason they have to penetrate into the deeper skin layers or permeate the skin. The outermost layer of the human skin, the stratum corneum, is responsible for its barrier function. Most topically administered drugs do not have the ability to penetrate the stratum corneum. In these cases modulations of the skin penetration profiles of these drugs and skin barrier manipulations are necessary. A skin penetration enhancement can be achieved either chemically, physically or by use of appropriate formulations. Numerous chemical compounds have been evaluated for penetration-enhancing activity, and different modes of action have been identified for skin penetration enhancement. In addition to chemical methods, skin penetration of drugs can be improved by physical options such as iontophoresis and phonophoresis, as well as by combinations of both chemical and physical methods or by combinations of several physical methods. There are cases where skin penetration of the drug used in the formulation is not the aim of the topical administration. Penetration reducers can be used to prevent chemicals entering the systemic circulation. This article concentrates on the progress made mainly over the last decade by use of chemical penetration enhancers. The different action modes of these substances are explained, including the basic principles of the physical skin penetration enhancement techniques and examples for their application.

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The skin is the largest organ of the body, whose main function is to protect the body against the loss of physiologically important components as well as harmful environmental insults. From the inside to the outside, the skin comprises three major structural layers: the hypodermis, the dermis and the epidermis. The epidermis contains four different sublayers, the stratum corneum (SC), stratum granulosum, stratum spinosum and stratum basale, where the barrier function of the skin mainly lies in the outermost layer of the epidermis, the SC. The SC contains corneocytes that are embedded in a lipid matrix existing in the form of lipid bilayers. The lipid bilayers are formed mainly from ceramides, free fatty acids and cholesterol, constitute the only continuous pathway across the SC and are responsible for the barrier function of the skin. However, the depletion or disturbance of SC lipids in the SC leads to a perturbation of the barrier function of the skin, and, conversely, several skin diseases such as psoriasis and atopic dermatitis are associated with the depletion of these SC lipids. Therefore, it is of paramount importance to understand the interrelationship between the depletion of SC lipids and skin diseases as well as factors that affect the composition and organization of SC lipids in order to assess the potential benefit of a direct replacement of the missing SC lipids as a means of treating affected, aged or diseased skin. i 2014 S. Karger AG, Basel

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