This study is the continuation of our research into vitamin C and its possible effects on human skin after topical administration. The effects of ascorbic acid, iron ions and UV irradiation on stratum corneum lipid models were investigated. The lipid models used were: a simple system (linolenic acid dispersion), a complex system (liposomes consisting of dipalmitoylphosphatidylcholine, cholesterol and linolenic acid) and complex systems with additionally incorporated ceramides (types III and IV). The lipid peroxidation was quantified by the thiobarbituric acid assay. A human adult low-calcium high-temperature (HaCaT) keratinocytes cell culture was used as a second in-vitro model. The amount of intracellular peroxides was determined by measuring the fluorescence intensity using the dihydrorhodamine 123 assay. Electron paramagnetic resonance spectroscopy was used to study the influence of ascorbic acid and iron ions on the signal intensity of 5-doxylstearic acid during UV exposure. Ascorbic acid showed prooxidative properties in the thiobarbituric acid assay whereas cell protection was measured in the HaCaT keratinocytes experiments. Electron paramagnetic resonance investigations revealed different extents of free radical production generated by iron ions, ascorbic acid and UV irradiation. In evaluating the results from this study new aspects of the mechanism of lipid damage caused by these three factors were suggested, transcending the simple redox behaviour of ascorbic acid.

The crude extracts of the leaves of Dodonaea viscosa and Rumex nervosus as well as of the root of Rumex abyssinicus were tested for anti-microbial and anti-inflammatory activities. It was observed that the three plants possess antibacterial activity against Streptococcus pyogenes and Staphylococcus aureus and strong activity against Coxsackie virus B3 and influenza A virus. In contrast, none of them exhibited anti-fungal activity. The anti-inflammatory activity test results verified that only R. abyssinicus inhibited the synthesis of prostaglandin (PG) E(2).

Our body uses an intelligent system to protect the skin from external influences and to prevent a total loss of water. To format and maintain the epidermal barrier function an approximately equimolar mixture of free fatty acids, ceramides and cholesterol is necessary. These lipids were synthesised in the living layers of the epidermis, incorporated into lamellar bodies and transported to the stratum corneum. Under the influence of hydrolytic active enzymes (glycosidases, phospholipases, sulfatases, sphingomyelinases and esterases) lipids were liberated from the transport form to the free form and secreted at the junction of the stratum granulosum to the stratum corneum [1, 2]. The review reports about influences of different drugs on the lipid synthesis.

Ketoprofen (KP) is a potent nonsteroidal anti-inflammatory drug. However, application to the skin is problematic because the photosensitizing properties of the benzophenone moiety may cause phototoxic effects when the treated skin region is exposed to UVA light. Using capillary electrophoresis with electrochemical detection we are able to differentiate the peroxides formed during illumination of KP-containing solutions of linoleic acid. Contrary to other profens a high amount of hydrogen peroxide was found among the reaction products. For investigation of the skin damaging effect human keratinocytes were used as models. Cell viability, DNA synthesis efficiency and intracellular concentration of peroxides were determined. Viability and proliferation behavior was not altered under the influence of KP. While lower concentrations of KP (10–100 nM) led to a protection against the UVA-induced (8 J/cm2) cell proliferation damage, higher concentrations (10–100 μM) led to an amplification of the proliferation decrease. With UVB irradiation at relevant doses the effects were lower than using UVA. Furthermore, intracellular peroxide content was increased after UV irradiation and KP addition. In conclusion some efforts have to be done to avoid these side effects in the use of KP for topical or transdermal application.

The efficacy of a medicinal agent presupposes its accumulation at the desired site of action. The active ingredient must therefore penetrate the skin barrier, the stratum corneum. This compact epidermal layer acts as a barrier to the penetration of substances; its effectiveness depends on regional variation and disease-related charges. From the therapeutic viewpoint the pharmaceutical agent should penetrate as rapidly as possible. This promotes the development of a rapid release vehicle with an optimised concentration-time profile for the active agent at the site of action. If the desired effect is to be maintained, a vehicle with an additional delayed action should be selected (e.g. nano particles). Although several different vehicles (e.g. o/w and w/o emulsions) were previously necessary to achieve this goal, colloidal drug vehicle systems are able to combine these properties. Their advantages are not only in the field of improved penetration but also in the controlled release of the active substance. Even active agents with unfavourable properties for cutaneous penetration (poor solubility, hydrophilic molecules, heat-, oxidation- or photo-sensitive substances) can be expected to be more effective. Not only the action of the drug itself, but also the effect of the vehicle system components are important. On the one hand they function as penetration modulators and on the other hand they can produce a more precise therapeutic benefit by their interaction with keratinocytes. Depending on their composition, vehicles without active ingredients can have considerable success in the treatment of various dermatoses (influence on proliferation, improvement of barrier function) or in cosmetic applications (hydration of the epidermis). As a result of increasing research into colloidal drug vehicle systems, positive impulses for use in dermatology or cosmetics can be expected.

An HPLC electrospray mass spectrometric method for the specific and sensitive quantification of Capsaicin [404-86-4] and Dihydrocapsaicin [19408-84-5] in extracts from human skin is presented.A 2 mm RP18 column was used with a mobile phase of methanor/water/acetic acid 90/9/1 at a flow rate of 0.2 mL/min. The reached limit of detection was 500 pg/mL. MS/MS and MS3 experiments were performed using an ion trap mass spectrometer. The fragmentation pattern in the positive mode is explained. The method was applied to study Capsaicin penetration from different pharmaceutical preparations.

During the last years interest was focused on the development of modifiers and vehicle system to influence drug penetration into the skin. It was searched for enhancers to specifically increase uptake either via the hydrophilic or via the lipophilic pathway through the stratum corneum. It has also been started to synthesize specific compounds (retaders/reducers) to decrease the penetration of lipophilic drugs with a high rate and extent of uptake into the skin to reduce systemic side effects. Furthermore, a lot of research work has been done to design new effective vehicle systems in order to modify drug penetration into the skin. These studies were started using liposomes. In the last years colloidal vehicle systems such as microemulsions, nanoparts and -capsules were included in the spectrum of dermal therapeutics. For this purpose, lyotropic mesogenic phases also are to be used.

1. BM 12.434 was compared with a known beta-adrenoceptor-blocking agent, metipranolol, and a combination of metipranolol and isosorbide-5-mononitrate in healthy volunteers. BM 12.434 and metipranolol were given in equi-effective beta-adrenoceptor-blocking doses (reduction of exercise-increased pulse--pressure product). 2. Responses of the cardiovascular system were determined by non-invasive methods. 3. BM 12.434 increased the peripheral resistance less than metipranolol. 4. After BM 12.434, in contrast to metipranolol, both arterial flow and the venous capacity showed significant increase. 5. The combination of isosorbide-5-mononitrate and metipranolol differed from metipranolol alone mainly by the effect on venous capacity, which showed a slight increase. 6. BM 12.434 is a beta-adrenoceptor-blocking agent whose additional actions on the veins and arteries are potentially useful for the treatment of both coronary heart disease and of arterial hypertension.