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ZusammenfassungIn den letzten Jahren sind die Hautkrebsraten weltweit gestiegen. Die Anwendung von Sonnenschutzmitteln ist eine weit verbreitete Strategie in der Prävention gegen Hautkrebs, Sonnenbrand und Photoalterung. Es sollten kombinierte Breitbandfiltersysteme mit hoher Wirkung gegen UV-B- und UV-A-Strahlung eingesetzt werden. Weitere Studien sind notwendig, um die Entwicklung von Sonnenschutzmitteln gegen die ebenfalls schädlichen IRA-Strahlen voranzutreiben. Obwohl die regelmäßige Anwendung von Sonnenschutzmitteln ein wesentlicher Bestandteil in der Hautkrebsprävention ist, sollten insbesondere bei Kindern kombinierte Schutzmaßnahmen angewendet werden: Sonnenkarenz bei starker Sonneneinstrahlung, textiler Sonnenschutz, Aufenthalt im Schatten und die Anwendung von Sonnenschutzmitteln.

Background Skin diseases can develop upon disadvantageous microclimate in relation to skin contact with textiles of supporting devices. Increased temperature, moisture, mechanical fracture, pressure, and inflammatory processes often occur mutually and enhance each other in their adverse effects. Therefore, the early prevention of skin irritations by improvement of microclimatic properties of skin in contact with supporting devices is important. Materials and methods In this study, the microclimate under occlusion with polyester, cotton, chloroprene rubber, and silicone textiles, used for supporting devices, was analyzed by determining several characteristic physiologic skin parameters in vivo, including temperature, moisture, and transepidermal water loss (TEWL). This is achieved by comparing a miniaturized in vivo detection device with several established optical and sensory methods in vivo. Results A highly significant TEWL decrease was found after polyester, chloroprene rubber, and silicone application. The application of all materials showed highly significant decrease in skin surface temperature, with chloroprene rubber showing the lowest. Similarly, all materials showed highly significant increase in relative moisture, where the highest increase was found for chloroprene rubber and silicone and the lowest increase for cotton. The cutaneous carotenoid concentration of chloroprene rubber, silicone, and polyester decreased. A manipulation of the surface structure of the stratum corneum was recognized for all materials except for cotton by laser scanning microscopy. Conclusion The skin parameters temperature, relative moisture, antioxidant status, and TEWL can effectively characterize the microclimatic environment during occlusion with medical supporting materials. These parameters could potentially be used to develop standardized testing procedures for material evaluation.

Nanoparticles can be applied to the hair follicles, which can serve as reservoirs for triggered drug release. A valid measurement method for the determination of the pH within the hair follicle in vivo has not been shown yet. Here, melamine formaldehyde particles up to 9 µm in size were applied on 40 freshly plucked scalp hairs of eight individuals to determine the pH along the hair shaft down to the root area of the hair. For fluorescent pH indicators, pyranine and Nile blue were incorporated into the particles. Measurements were conducted using confocal laser scanning microscopy. A pH decay gradient could be found from the hair sheath towards the external hair shaft (p = 0.012) with pH values at the hair sheath of 6.63 ± 0.09, at the hair sheath end at 6.33 ± 0.11, and at the external hair shaft at 6.17 ± 0.09 (mean ± SE). The pH difference between the hair sheath end and the external hair shaft was found to be significant (p = 0.036). The results might be comparable with the pH within the hair follicle in vivo indicating a pH increase towards the hair root.

Hair follicles can serve as an effective reservoir for dermal drug delivery upon the topical application of particulate substances. Here, the follicular penetration of an indodicarbocyanine-labelled thermoresponsive nanogel (189 nm) having a cloud point temperature of 34°C and linked via an acid-labile linker to the model drug indocarbocyanine was investigated. In total, 227 hair follicles of porcine ear skin were examined after topical application of the thermoresponsive nanogels at room temperature (21°C), physiological skin surface temperature (32°C) and core body temperature (37°C) for the follicular penetration depths of indodicarbocyanine and indocarbocyanine using confocal laser scanning microscopy. The results showed a significantly increased mean follicular penetration of the carrier to a depth of 298.8±85.8 μm after incubation at 37°C compared to samples incubated at 21°C and 32°C with mean follicular penetration depths of 202.7±81.7 μm and 219.4±52.9 μm, respectively (p

The motion of a single rigid nanoparticle inside a hair follicle is investigated by means of Brownian dynamics simulations. The cuticular hair structure is modeled as a periodic asymmetric ratchet-shaped surface. Induced by oscillating radial hair motion we find directed nanoparticle transport into the hair follicle with maximal velocity at a specific optimal frequency and an optimal particle size. We observe flow reversal when switching from radial to axial oscillatory hair motion. We also study the diffusion behavior and find strongly enhanced diffusion for axial motion with a diffusivity significantly larger than for free diffusion.

Hair follicle research is currently focused on the development of drug-loaded nanocarriers for the targeting of follicular structures in the treatment of skin and hair follicle-related disorders. In the present study, a dual-label nanocarrier system was implemented in which FITC-labeled BSA hydrogel nanocarriers loaded with the model drug and dye TRITC-dextran were applied topically to porcine ear skin. Follicular penetration and the distribution of both dyes corresponding to the nanocarriers and the model drug in the follicular ducts subsequent to administration to the skin were investigated using confocal laser scanning microscopy. The release of TRITC-dextran from the particles was induced by washing of the nanocarriers, which were kept in a buffer containing TRITC-labeled dextran to balance out the diffusion of the dextran during storage, thereby changing the concentration gradient. The results showed a slightly but statistically significantly deeper follicular penetration of fluorescent signals corresponding to TRITC-dextran as opposed to fluorescence corresponding to the FITC-labeled particles. The different localizations of the dyes in the cross-sections of the skin samples evidenced the release of the model drug from the labeled nanoparticles.

Antioxidants like carotenoids play a major role in the prevention of the destructive influence of free radicals in our skin. Carotenoids, as well as all other antioxidants, are substantial substances which must be supplied by nutrition. Resonance Raman spectroscopy (RRS) allows measurement of the carotenoid content of eggs, representing a rich carotenoid source in our nutrition. A previous study showed that eggs from organic production contain higher carotenoid levels in contrast to eggs from conventionally housed chicken. The uptake of these organically produced eggs led to an increased antioxidant concentration in the skin. In this study, the effects of different storage modalities, conservation techniques, and the effects of food processing on the carotenoid levels in eggs were investigated with RRS. Common storage modalities and preservation techniques showed only a limited influence on egg-derived carotenoid concentrations. However, a colder environment (at least for shell eggs) and high-pressure preservation had the best preservative influence on the carotenoid content. Surprisingly, food processing such as boiling increased the carotenoid concentration in eggs, whilst broiling destroyed the carotenoids almost completely. In conclusion, RRS is suitable for monitoring egg-derived carotenoid levels, and carotenoid levels in eggs are generally stable under common storage and preservation modalities. Boiling in contrast to broiling of eggs might be superior in terms of carotenoid preservation within food processing.

The interactions of nanoparticles with skin and skin cells are complex and depend on the nanoparticle type. The present work provides an overview on the interactions between solid nanoparticles including silica, titanium dioxide, and silver particulates and skin and skin cells on the basis of previous research results. Generally, nanoparticles applied to skin tend to remain on the skin surface and penetrate only into the upper layers of the stratum corneum and the follicular ducts. In very few cases, nanoparticles have been found in deeper skin layers, particularly if the skin barrier was previously disrupted. Increased nanoparticle penetration may result in biologically relevant effects, e.g. cytotoxic cellular effects induced by silver ions released from wound dressings incorporating silver nanoparticles.

In view of globally rising skin cancer rates and harmful effects exerted by sunlight throughout the ultraviolet, visible and infrared ranges, an objective, safe and comprehensive method for determining sunscreen efficacy is required in order to warrant safe sun exposure. In this study, the influence of characteristic active ingredients (chemical filters, physical filters and antioxidants) on different sunscreen indicators, including the universal sun protection factor and the radical formation ratio, was determined and compared to their influence on sun protection factor values. Spectroscopic universal sun protection factor measurements were conducted ex vivo by analyzing tape strips taken from human skin, and radical formation ratio determination was performed via electron paramagnetic resonance spectroscopy using porcine ear skin ex vivo. The sun protection factor determination was conducted according to ISO standards (ISO 24444:2010). It was shown that chemical filters provide a protective effect which was measurable by all methods examined (spectroscopy, electron paramagnetic resonance spectroscopy and erythema formation). Physical filters, when used as single active ingredients, increased protective values in universal sun protection factor and sun protection factor measurements but exhibited no significant effect on universal sun protection factor measurements when used in combination with chemical filters or antioxidants. Antioxidants were shown to increase sun protection factor values. Radical formation ratio values were shown to be influenced merely by chemical filters, leading to the conclusion that the universal sun protection factor is the most suitable efficacy indicator for the ultraviolet range.

Das Hand- und Fussyndrom, auch bekannt als palmoplantare Erythrodysasthesie, beschreibt eine kutane Nebenwirkung unter einer Reihe von Chemotherapeutika, deren Symptome unter Umstanden zum Therapieabbruch und zu der Notwendigkeit von zusatzlichen medizinischen Masnahmen fuhren konnen. Die zumeist palmar und plantar auftretenden, teils schmerzhaften, erythematosen Hautveranderungen haben, je nach Auspragung, eine teils erhebliche Einschrankung der Lebensqualitat betroffener Patienten zur Folge. Da die Symptome des Hand- und Fussyndroms unter einer Chemotherapie in den meisten Fallen einen progredienten Verlauf zeigen, stellte die Dosismodifikation bzw. eine Pausierung oder gar ein Abbruch der Chemotherapie bisher haufig die einzige effiziente Therapiemasnahme dar. Aktuelle Studien deuten jedoch darauf hin, dass die begleitende topische Applikation von hoch konzentrierten, kombinierten Antioxidantien eine effektive Praventions- und Behandlungsstrategie des Hand- und Fussyndroms darstellt.

Background/Aims: Airborne pollutants, such as nano-sized soot particles, are increasingly being released into the environment as a result of growing population densities and industrialization. They can absorb organic and metal compounds with potential biological activity, such as polycyclic aromatic hydrocarbons and airborne pollen allergens. Local and systemic toxicities may be induced in the skin if the particulates release their harmful components upon dermal contact. Methods: In the present study, skin pretreatments with serum and/or shield as barrier formulations prior to exposure and washing with a cleanser subsequent to exposure were evaluated as a protection and decontamination strategy using laser scanning microscopy. Results: The results indicate that while the application of serum and a cleanser was insufficient for decontamination, the pretreatment with shield prior to nanoparticle exposure followed by washing led to the removal of a considerable amount of the carbon black particles. The combined application of serum and shield before the administration of carbon black particles and subsequent washing led to their elimination from the skin samples. Conclusion: The application of barrier-enhancing formulations in combination with a cleanser may reduce the penetration of harmful airborne particulates by preventing their adhesion to the skin and facilitating their removal by subsequent washing with the cleanser.

Two state-of-the-art microscopic optical methods, namely, confocal laser scanning microscopy in the fluorescence and reflectance regimes and multiphoton tomography in the autofluorescence and second harmonic generation regimes, are compared for porcine skin ex vivo and healthy human skin in vivo. All skin layers such as stratum corneum (SC), stratum spinosum (SS), stratum basale (SB), papillary dermis (PD) and reticular dermis (RD) as well as transition zones between these skin layers are measured noninvasively at a high resolution, using the above mentioned microscopic methods. In the case of confocal laser scanning microscopy (CLSM), measurements in the fluorescence regime were performed by using a fluorescent dye whose topical application on the surface is well suited for the investigation of superficial SC and characterisation of the skin barrier function. For investigations of deeply located skin layers, such as SS, SB and PD, the fluorescent dye must be injected into the skin, which markedly limits fluorescence measurements using CLSM. In the case of reflection CLSM measurements, the obtained results can be compared to the results of multiphoton tomography (MPT) for all skin layers excluding RD. CLSM cannot distinguish between dermal collagen and elastin measuring their superposition in the RD. By using MPT, it is possible to analyse the collagen and elastin structures separately, which is important for the investigation of anti-aging processes. The resolution of MPT is superior to CLSM. The advantages and limitations of both methods are discussed and the differences and similarities between human and porcine skin are highlighted.

The aim of the present study was to solve the water insolubility limitation of the medically and cosmetically interesting substance Garcinia mangostana Linn (GML) extract by encapsulation, and to evaluate and investigate the penetration efficacy of free and encapsulated GML in two different vehicles (water and cream) in porcine ear skin. The follicular penetration depth was determined in 50 hair follicles for each of the four formulations by means of fluorescence microscopy. Tape stripping was used to compare the distribution properties of GML with all formulations on the stratum corneum. The results showed that encapsulated and free GML in the cream base penetrated deeper into hair follicles than if applied in an aqueous base. In addition, encapsulated GML could be distributed more homogeneously on the stratum corneum than the free GML. In conclusion, it was found that encapsulated GML in a cream base had the most effective penetration level in porcine ear skin.

Palmoplantar erythrodysesthesia (PPE) is one of the most frequent side effects during systemic treatment with pegylated liposomal doxorubicin (PLD, Caelyx®). PPE lesions show a range of symptoms, from numbness to painful erosions, and can have a major impact on the quality of life in affected patients. Previously, a possible pathomechanism of PPE was found in doxorubicin-treated patients based on radical formation in the skin. Here, a preventive strategy using a topically applied ointment with a high radical protection factor was investigated. In this randomized placebo-controlled double-blind study the antioxidant-containing ointment was compared with a placebo ointment regarding PPE grade III occurrence, overall PPE grade I–III occurrence and PPE severity in PLD patients. The verum or placebo cream was topically applied for a period of 16 weeks, starting 3 days prior to the first cycle of chemotherapy. Clinical evaluations were carried out by a dermatologist prior to the first cycle of chemotherapy and every 4 weeks for the duration of 16 weeks. Thirty-two patients were enrolled in total, of which 17 (66%) completed the study. No PPE grade III was found in the verum group, while five out of seven patients (71%) had to be unblinded in the placebo arm due to PPE grade III (p = 0.003). General PPE occurrence of all grades was 60% under verum and 86% under placebo treatment. The preventive application of an antioxidant-containing ointment was shown to be significantly more effective in the prevention of PPE grade III compared to placebo treatment.

More and more investigations confirm that nanoparticles are incapable of overcoming the intact skin barrier in vivo. Do nanoparticles still have a future in dermal drug delivery? Unlike many other topically applied substances, nanoparticles have not been reported to utilize the intercellular penetration pathway and preferentially make use of the follicular penetration pathway. Deep penetration into the follicular ducts has been described for a variety of particles and appears to be strongly influenced by particle size. For targeted drug delivery, smart nanoparticles are required which are able to release their loaded drugs subsequent to internal or external trigger stimuli, and thereby enable the translocation of the active agents into the viable epidermis. In the recent manuscript, three nanoparticles systems are summarized and compared which release their model drugs upon different trigger mechanisms. The BSA hydrogel nanoparticles release their model drug TRITC-dextran by passive diffusion due to a concentration gradient via a porous surface. The protease-triggered controlled release BSA nanoparticles release their model drug if they are applied simultaneously with protease nanoparticles, resulting in an enzymatic degradation of the particles and a release of the model drug FITC. Finally, the IR-triggered controlled release AuNP-doped BSA nanoparticles release their model drug FITC after photoactivation with wIRA. For all three nanoparticle systems, the release of their model drugs could be observed. For the first nanoparticle system, only low follicular penetration depths were found which might by due do an agglomeration effect. For the last two nanoparticle systems, deep follicular penetration and even an uptake by the sebaceous glands were verified. In conclusion, it could be demonstrated that nanoparticles do have a future in dermal drug delivery if smart nanoparticle systems are utilized which are able to release their drug at specific times and locations within the hair follicle.

Background In humans, topically applied nanocarriers penetrate effectively into the hair follicles where they can be exploited for the localized and targeted treatment of skin disorders. Objective The objective of the present study was to examine the applicability of particle-based systems for follicular drug delivery in companion animals and livestock, which have a large follicular reservoir. Animals Skin samples from 10 beagle dogs, 14 Wistar rats and four ears from freshly slaughtered cross-bred pigs were used. Methods Fluoresceinamine labelled poly (L-lactide-co-glycolide) nanocarriers (256 or 430 nm) were applied on the different skin samples. After penetration, skin biopsies were removed and cryohistological cross sections prepared and investigated with regard to the follicular penetration depths (in μm ± standard deviation) of the nanocarriers using confocal laser scanning microscopy. Results In canine, rat and porcine hair follicles, the smaller nanoparticles were detected at mean follicular penetration depths of 630.16 ± 135.75 μm, 253.55 ± 47.36 μm and 653.40 ± 94.71 μm, respectively. The larger particles were observed at average follicular depths of 604.79 ± 132.42 μm; 262.87 ± 55.25 μm and 786.81 ± 121.73 μm, respectively, in canine, rat and porcine hair follicles. Statistically significant differences (P < 0.05) in the mean follicular penetration depths of the differently sized nanocarriers could be determined for the canine and porcine skin samples. Conclusion The mean follicular penetration depths of the differently sized nanocarriers were mostly significantly different between the different species, which might be due to different species-specific follicular dimensions. This issue needs to be addressed specifically in further studies.

The application of particles in dermatology and cosmetology represents an emerging field and is closely connected with the question of risk assessment as the potential for, and consequences of, penetration of such particles into the living tissue has not been determined conclusively. In the medical sector, extensive research activities are in progress to develop particles, which can be used as efficient carriers for drug delivery through the skin barrier. In contrast, in cosmetic products, particles are mostly required to remain on the skin surface to fulfill their beneficial effect. Whereas the intercellular penetration of particles seems to be unlikely, the hair follicle has been shown to be a relevant penetration pathway for particles as well as an important long-term reservoir. It has been demonstrated that the penetration depth of the particles can be influenced by their size resulting in the possibility of a differentiated targeting of specific follicular structures. In the present review, the follicular penetration mechanisms and storage properties of particles are discussed.

Hair follicles represent interesting target sites for topically applied substances such as topical vaccinations or agents used in the field of regenerative medicine. In recent years, it could be shown that particles penetrate very effectively into the hair follicles. In the present study, the influence of particle size on the follicular penetration depths was examined. The penetration depths of two different types of particles sized 122 to 1000 nm were determined in vitro on porcine skin. The results revealed that the particles of medium size (643 and 646 nm, respectively) penetrated deeper into the porcine hair follicles than smaller or larger particles. It was concluded that by varying the particle size, different sites within the porcine hair follicle can be targeted selectively. For the human terminal hair follicle, the situation can be expected to be similar due to a similar size ratio of the hair follicles.

The Organization for Economic Cooperation and Development (OECD) recommends caffeine as a reference substance for in vitro skin absorption tests using Franz diffusion cells (FDC). However, it has not been possible to investigate the follicular penetration pathway using this method until now. The aim of this study was to develop a technique to allow the examination of the follicular penetration pathway of a substance penetrating into the skin. The OECD standard method was therefore combined with the follicle closing technique (FCT), an established in vivo method. By using test skin of varying follicular densities, different penetration values were obtained for the test substance caffeine. The follicular penetration rate was determined by an indirect calculation after modifying the in vivo FCT for use in the in vitro FDC. This method is the first to allow the differentiation of penetration pathways by combining the OECD standard method (using the FDC) and the FCT. Caffeine showed a surprisingly high rate of penetration through the follicular shunts in vitro.

AIMS Due to ethical reasons, in vivo penetration studies are not applicable at all stages of development of new substances. Therefore, the development of appropriate in vitro methods is essential, as well as the comparison of the obtained in vivo and in vitro data, in order to identify their transferability. The aim of the present study was to investigate the follicular penetration of caffeine in vitro and to compare the data with the in vivo results determined previously under similar conditions. METHODS The Follicular Closing Technique (FCT) represents a method to investigate the follicular penetration selectively. In the present study, FCT was combined with the Franz diffusion cell in order to differentiate between follicular and intercellular penetration of caffeine into the receptor medium in vitro. Subsequently, the results were compared with the data obtained in an earlier study investigating follicular and intercellular penetration of caffeine in vivo. RESULTS The comparison of the data revealed that the in vitro experiments were valuable for the investigation of the follicular penetration pathway, which contributed in vivo as well as in vitro to approximately 50% of the total penetration, whereas the kinetics of caffeine penetration were shown to be significantly different. CONCLUSIONS The combination of FCT with the Franz diffusion cell represents a valuable method to investigate follicular penetration in vitro. Nevertheless, in vivo experiments should not be abandoned as in vitro, structural changes of skin occur and blood flow and metabolism are absent, probably accounting for reduced penetration rates in vitro.

Laser scanning microscopy and tape stripping, in combination with optical methods, were used to analyze the distribution and penetration of a barrier cream into the horny layer (stratum corneum) of the human skin under in vivo conditions. The barrier cream contained microparticles of 10 – 100 μm loaded with antioxidant substances. The cream was designed for protection of the skin surface against the destructive action of free radicals, produced by systemically applied chemotherapeutic agents reaching the skin surface via the sweat. Both methods were able to demonstrate that the barrier cream was distributed homogeneously on the skin surface forming a protection film. A penetration into deeper parts of the stratum corneum (SC) was not observed.

In recent years, hair follicles have attracted much attention in several fields of research. Representing complex and dynamic three-dimensional structures, which undergo highly specific growth cycles, the hair follicles are susceptible to several disturbances, for example, infectious diseases, various forms of hair loss, autoimmune diseases, androgen-associated diseases and skin tumors. Consequently, they are increasingly considered to be relevant drug targets and to represent drug delivery routes through the stratum corneum into deeper skin layers. The effectiveness of follicular or even transfollicular penetration depends on not only the penetrating substance or on its vehicle, but also on follicular density, size and reservoir, as well as on the activity status of the hair follicle. Follicular targeting, ideally topical delivery of substances to specific compartments and cell populations within the hair follicles, offers opportunities in the treatment of hair follicle-associated diseases, immunotherapy and even gene therapy, as the bulge region of the hair follicle represents a reservoir of stem cells. This present paper gives an overview of the recent developments in the fascinating field of hair follicles, their disorders and their opportunities.

In the past, it was assumed that the intercellular route was the only relevant penetration pathway for topically applied substances. Recent results on follicular penetration obtained at the Center for Experimental and Applied Cutaneous Physiology, Charité – Universitätsmedizin Berlin, Germany, emphasize that the hair follicles represent a highly relevant and efficient penetration pathway and reservoir for topically applied substances.

In the present study, the ability of a shampoo formulation containing caffeine as well as the fluorescent dye fluorescein to penetrate into hair follicles was investigated by in vivo laser scanning microscopy. A contact time of two minutes between the shampoo and the skin surface was sufficient for the formulation to penetrate deeply into the hair follicles and to remain there for up to 48 hours, even after washing. As hair follicles are surrounded by a close network of capillaries, dendritic cells and stem cells, they represent an important target for drug delivery. The results of the present study demonstrated that in vivo laser scanning microscopy is an efficient tool for the investigation of the dermatopharmacokinetics of topically applied molecules and their penetration pathways, as the method yields space- and time-resolved measurements.

Alterations of the skin microvasculature are known to play an important role in the development and maintenance of psoriatic skin lesions. In this study, we investigated lesional skin in 11 psoriatic patients during a modified Goeckerman treatment using reflectance confocal microscopy (RCM) to study the relationship between clinical clearance and histological normalization of psoriatic skin and the significance of histological abnormalities on the course of disease. The treatment regimen resulted in a significant reduction of the Psoriasis Area and Severity Index (PASI) as well as capillary and papillary diameters (p < 0.0001). The capillary and papillary diameters were still enlarged when compared to those in normal skin (p < 0.001). Capillary and papillary diameters correlated with each other prior to and after treatment (correlation coefficient = 0.63 and 0.64, p = 0.01 and 0.002, respectively) but not with the PASI. Capillary and papillary diameters after treatment and percentage reduction of the PASI during treatment seemed to be better predictors for the clinical course of relapse than the PASI after treatment. These findings make the subclinical changes of psoriatic skin vessels and dermal papillae a legitimate target for treatment. Further investigations of a large group of patients are needed to evaluate the potential of RCM findings as successor of the PASI in the monitoring of psoriasis.

Various milling methods result in different particle size distributions and, in combination with mash and thermal treatment (expandate) of the feed, may have an impact on nutrient digestibility, pH of the digesta and subsequently the performance of an animal. Since this aspect has not been widely considered in laying hens, the objective of the present study was to investigate the effects of milling method, expansion, and particle size of feed on performance, apparent ileal nutrient digestibility, and pH of digesta in laying hens. Twelve variants of the same diet were produced. Four different milling techniques (hammer mill, roller mill, disc mill, and wedge-shaped disc mill) were used to grind the feed cereals. Coarse feed was obtained from all four mills. Additionally, fine feed was obtained from the hammer mill and the roller mill. Each of the six feed variants was offered as mash or expandate, resulting in a total of 12 treatments. The duration of the experimental period was 21 days. A total of 576 layers, each 19 weeks of age, were used in eight replicates. The statistical analysis for the four milling methods and two thermal treatments was performed using a 4×2 factorial arrangement. The effect of particle size was investigated using a 2×2×2 factorial arrangement including the coarse and fine particle sizes that were produced with the hammer mill and the roller mill as well as the mash and expandate. The animal performance and the pH of the digesta were not affected by the treatments. Ileal digestibility of starch was significantly improved by feeding mash compared to expandate (P=0.013) and by feeding coarse compared to fine feed (P=0.028). Based on this study, the tested milling methods can be used for the production of feed for laying hens without affecting performance and digestibility of nutrients.

During the past decades, encouraging progress has been made in the prevention of surgical site infections (SSI). However, as SSI still occur today, strategic prevention measures such as standardized skin antisepsis must be implemented and rigorously promoted. Recent discoveries in skin physiology necessitate the development of novel antiseptic agents and procedures in order to ameliorate their efficacy. In particular, alternate target structures in the skin need to be taken into consideration for the development of the next generation of antiseptics. Recent investigations have shown that a high number of microorganisms are located within and in the close vicinity of the hair follicles. This suggests that these structures are an important reservoir of bacterial growth and activity in human skin. To date, it has not been fully elucidated to what extent conventional liquid antiseptics sufficiently target the hair follicle-related microbial population. Modern technologies such as tissue-tolerable plasma (TTP) have been tested for their potential antiseptic efficiency by reducing the bacterial load in the skin and in the hair follicles. First experiments using liposomes to deliver antiseptics into the hair follicles have been evaluated for their potential clinical application. The present review evaluates these two innovative methods for their efficacy and applicability in preoperative skin antiseptics.

An efficient penetration and long-term storage of topically applied substances is important for drug delivery in medical treatment and cosmetics. It has recently become apparent that the hair follicles represent an efficient and long-term reservoir for topically applied substances. It was found that particles sized 300–600 nm penetrate more efficiently into the hair follicles than smaller or larger particles. In the present paper, the hair surface structure of human and porcine hairs was analyzed by electron microscopy. It could be observed that the thickness of the cuticula corresponds to the optimal size of the nanoparticles for penetration into the hair follicles. Additionally, it could be demonstrated that the cuticula of human vellus and terminal hairs were of similar thickness (approx. 530 nm), while the thickness of the cuticula obtained from porcine ear bristles were slightly thinner (approx. 320 nm).

Variation in the level of the carotenoid antioxidant substances beta-carotene and lycopene in the human skin of ten healthy volunteers was measured with resonance Raman spectroscopy in an in vivo experiment over the course of 12 months. Information on the lifestyle of the volunteers concerning dietary supplementation and stress factors was obtained daily by the completion of questionnaires. The results showed individual variations in the levels of carotenoid antioxidant substances in the skin of the volunteers, which strongly correlated to specific lifestyles, such as the intake of dietary supplementations rich in carotenoids, and the influence of stress factors. A carotenoid-rich nutrition, based on large amounts of fruit and vegetables, increased the measured carotenoid levels of skin, while stress factors such as fatigue, illness, smoking, and alcohol consumption gave rise to a decrease in carotenoid levels of the skin. These decreases occurred relatively quickly over the course of one day, while the subsequent increases lasted for up to 3 days. During the summer and autumn months, an increase in the level of carotenoids in the skin was measured for all volunteers. The average "seasonal increase" of the carotenoid content in the skin was determined to be 1.26-fold.

The important role of hair follicles as penetration pathways and reservoir structures for topically applied compounds has been validated in numerous animal models as well as in humans. Follicular penetration rates are modulated by regional variations in size and proportions and the functional status. Advances have especially been made in the targeting of hair follicle-associated cell populations including antigen-presenting cells and stem cells. Improved investigative methods based on differential stripping, spectrophotometry and confocal laser scanning microscopy have led to the determination of the penetration profiles and kinetics for a multiplicity of drugs and drug delivery systems. The observation that particulate delivery systems aggregate and remain in hair follicle openings and their penetration along the follicular duct occurs in a size-dependent manner, which has led to advanced concepts of targeted drug delivery of bioactive compounds in the field of solid particles, as well as semi-solid particles, such as liposomes. This review summarizes the recent progress in this field, and underlines the necessity for pilot studies in human volunteers to further the development of clinical applications for follicular targeting.

For at least two decades, nanoparticles have been investigated for their capability to deliver topically applied substances through the skin barrier. Based on findings that nanoparticles are highly suitable for penetrating the blood–brain barrier, their use for drug delivery through the skin has become a topic of intense research. In spite of the research efforts by academia and industry, a commercial product permitting the nanoparticle-assisted delivery of topically applied drugs has not yet been developed. However, nanoparticles of approximately 600 nm in diameter have been shown to penetrate efficiently into the hair follicles, where they can be stored for several days. The successful loading of nanoparticles with drugs and their triggered release inside the hair follicle may present an ideal method for localized drug delivery. Depending on the particle size, such a method would permit targeting specific structures in the hair follicles such as stem cells or immune cells or blood vessels found in the vicinity of the hair follicles.

Hair follicles represent reservoirs for localized drug therapy and transport pathways for systemic drug delivery. This study describes an approach towards developing a novel procedure for quantifying topically applied substances located in the hair follicles of porcine ear skin, a model for human in vivo skin, using a fluorescent dye. Approximately 5% of the topically applied dye was recovered from the hair follicles, which is in accordance with a previous study.

Confocal laser scan microscopy (CLSM) has emerged as a tool for in vivo assessment of cutaneous conditions. In particular, its use in wound healing assessment has increasingly moved into focus. In this context, the application of tissue tolerable plasma (TTP) for wound treatment has recently become one of the most innovative therapeutic modalities.We analyzed wound healing parameters such as area decline and histomorphological characteristics of tissue repair in six subjects with vacuum-generated wounds on the forearm with a four-armed design: (A) no treatment, (B) treatment with TTP, (C) treatment with octenidine, and (D) sequential treatment with TTP and octenidine. Assessment of the wounds was conducted during six visits over the course of two weeks. The wounds were analyzed by photography and CLSM.TTP treatment led to a more rapid area decline that was statistically significant in comparison to other treatment groups. Besides mild pain, it was well tolerated. Morphologically, wound healing was found to initiate from the edges with the formation of dendritic structures consisting of keratinocytes.CLSM is a valuable tool for assessing the dynamics of wound healing. TTP, for reasons that still need to be investigated, can accelerate wound repair.

The removal of noxious particulate contaminants such as pollutants derived from particle-to-gas conversions from exposed skin is essential to avoid the permeation of potentially harmful substances into deeper skin layers via the stratum corneum or the skin appendages and their dispersion throughout the circulatory system. This study is aimed at evaluating the efficacy of using the silicone glycol polymer PEG-12 dimethicone and an absorbent textile material to remove fluorescing hydroxyethyl starch nanocapsules implemented as model contaminants from exposed porcine ear skin. Using laser scanning microscopy, it could be shown that while the application and subsequent removal of the absorbent textile material alone did not result in sufficient decontamination, the combined application with PEG-12 dimethicone almost completely eliminated the nanocapsules from the surface of the skin. By acting as a wetting agent, PEG-12 dimethicone enabled the transfer of the nanocapsules into a liquid phase which was taken up by the absorbent textile material. Only traces of fluorescence remained detectable in several skin furrows and follicular orifices, suggesting that the repeated implementation of the procedure may be necessary to achieve total skin surface decontamination.

Non-invasive skin analysis by optical coherence tomography (OCT) is limited because of the absorption and scattering properties of the tissue. There are several possibilities for enhancing OCT images. The purpose of this study was to demonstrate that image quality can be improved using the hyperosmolar agents glucose and glycerol while investigating human ridged and meshed skin areas, without causing damage to the tissue. The experiments were carried out on the palm and the forearm of ten volunteers. After application of the substances in the test area, the penetration depth and image contrast were measured at intervals of 5 min for a total duration of 60 min. Both agents clearly improved the OCT imaging depth in comparison to untreated human skin. The results demonstrated that glucose had a faster diffusion rate than glycerol. Consequently, it can be concluded that the treatment with glucose or glycerol for optical clearing of the skin tissue results in an improved image quality if applied 15–25 min prior to clinical testing.