Overcoming the stratum corneum: the modulation of skin penetration. A review.

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.

Mass spectrometric examinations of stratum corneum lipid models exposed to ultraviolet irradiation.

Lipid model systems consisting of the major components of the stratum corneum intercellular lipid matrix were studied to investigate the ultraviolet-radiation-mediated damage of these biomolecules. Pure lipids and liposomes were irradiated using a lamp emitting a solar radiation spectrum. The influences of the irradiation and the effects of added iron ions were studied by electrospray ionization mass spectrometry (MS) with an ion trap analyser. Exact mass measurements were carried out using a time-of-flight mass spectrometer. Only linolenic acid and cholesterol were found to be subject to oxidative changes caused by UV irradiation whereas the other lipids examined (dipalmitoylphosphatidylcholine, ceramide III and cholesterol sulphate) were stable to oxidative stress. Several lipid adducts were observed upon analysis of the liposomes. The composition of these adducts was identified by MS/MS experiments.

The examination of skin lipid model systems stressed by ultraviolet irradiation in the presence of transition metal ions.

In this study, we investigated the effects of ultraviolet (UV) radiation on lipid peroxidation in the presence of ionised iron as a transition metal. Fatty acids as important intercellular stratum corneum lipids and liposomes were used to model skin lipid systems for our experiments. A UV-A laser and a broad spectrum UV lamp were used to create high-level radiation. UV-related damage was quantified by the thiobarbituric acid assay detecting malondialdehyde. Electrospray mass spectrometry was used to characterise peroxidation products following UV exposure. We have shown that hydro- and endoperoxides are long stable intermediates deriving from lipid peroxidation. The incorporation of unsaturated fatty acids into phospholipid liposomes increased the average liposomal diameter and enhanced sensitivity to UV radiation. By comparing our data from laser induced monochromatic UV-A radiation and broad-spectrum UV irradiation, we have demonstrated that UV-A radiation can also induce lipid peroxidation in lipid model systems.