Dehydration of multilamellar fatty acid membranes: Towards a computational model of the stratum corneum

NASA Astrophysics Data System (ADS)

MacDermaid, Christopher M.; DeVane, Russell H.; Klein, Michael L.; Fiorin, Giacomo

2014-12-01

The level of hydration controls the cohesion between apposed lamellae of saturated free fatty acids found in the lipid matrix of stratum corneum, the outermost layer of mammalian skin. This multilamellar lipid matrix is highly impermeable to water and ions, so that the local hydration shell of its fatty acids may not always be in equilibrium with the acidity and relative humidity, which significantly change over a course of days during skin growth. The homeostasis of the stratum corneum at each moment of its growth likely requires a balance between two factors, which affect in opposite ways the diffusion of hydrophilic species through the stratum corneum: (i) an increase in water order as the lipid lamellae come in closer contact, and (ii) a decrease in water order as the fraction of charged fatty acids is lowered by pH. Herein molecular dynamics simulations are employed to estimate the impact of both effects on water molecules confined between lamellae of fatty acids. Under conditions where membrane undulations are energetically favorable, the charged fatty acids are able to sequester cations around points of contact between lamellae that are fully dehydrated, while essentially maintaining a multilamellar structure for the entire system. This observation suggests that the undulations of the fatty acid lamellae control the diffusion of hydrophilic species through the water phase by altering the positional and rotational order of water molecules in the embedded/occluded "droplets."

Lipid composition of the stratum corneum and cutaneous water loss in birds along an aridity gradient.

PubMed

Champagne, Alex M; Muñoz-Garcia, Agustí; Shtayyeh, Tamer; Tieleman, B Irene; Hegemann, Arne; Clement, Michelle E; Williams, Joseph B

2012-12-15

Intercellular and covalently bound lipids within the stratum corneum (SC), the outermost layer of the epidermis, are the primary barrier to cutaneous water loss (CWL) in birds. We compared CWL and intercellular SC lipid composition in 20 species of birds from desert and mesic environments. Furthermore, we compared covalently bound lipids with CWL and intercellular lipids in the lark family (Alaudidae). We found that CWL increases in birds from more mesic environments, and this increase was related to changes in intercellular SC lipid composition. The most consistent pattern that emerged was a decrease in the relative amount of cerebrosides as CWL increased, a pattern that is counterintuitive based on studies of mammals with Gaucher disease. Although covalently bound lipids in larks did not correlate with CWL, we found that covalently bound cerebrosides correlated positively with intercellular cerebrosides and intercellular cholesterol ester, and intercellular cerebrosides correlated positively with covalently bound free fatty acids. Our results led us to propose a new model for the organization of lipids in the avian SC, in which the sugar moieties of cerebrosides lie outside of intercellular lipid layers, where they may interdigitate with adjacent intercellular cerebrosides or with covalently bound cerebrosides.

Organization of lipids in avian stratum corneum: Changes with temperature and hydration.

PubMed

Champagne, Alex M; Allen, Heather C; Bautista-Jimenez, Robin C; Williams, Joseph B

2016-02-01

In response to increases in ambient temperature (Ta), many animals increase total evaporative water loss (TEWL) through their skin and respiratory passages to maintain a constant body temperature, a response that compromises water balance. In birds, cutaneous water loss (CWL) accounts for approximately 65% of TEWL at thermoneutral temperatures. Although the proportion of TEWL accounted for by CWL decreases to only 25% at high Ta, the magnitude of CWL still increases, suggesting changes in the barrier function of the skin. The stratum corneum (SC) is composed of flat, dead cells called corneocytes embedded in a matrix of lipids, many of which arrange in layers called lamellae. The classes of lipids that comprise these lamellae, and their attendant physical properties, determine the rate of CWL. We measured CWL at 25, 30, 35, and 40 °C in House Sparrows (Passer domesticus) caught in the winter and summer, and in sparrows acclimated to warm and cold lab environments. We then used Fourier transform infrared spectroscopy to measure lipid-lipid and lipid-water interactions in the SC under different conditions of temperature and hydration, and correlated these results with lipid classes in the SC. As CWL increased at higher temperatures, the amount of gauche defects in lipid alkyl chains increased, indicating that lipid disorder is partially responsible for higher CWL at high temperatures. However, variation in CWL between groups could not be explained by the amount of gauche defects, and this remaining variation may be attributed to greater amounts of cerebrosides in birds with low CWL, as the sugar moieties of cerebrosides lie outside lipid lamellae and form strong hydrogen bonds with water molecules. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Stratum corneum dysfunction in dandruff

PubMed Central

Turner, G A; Hoptroff, M; Harding, C R

2012-01-01

Summary Synopsis Dandruff is characterized by a flaky, pruritic scalp and affects up to half the world’s population post-puberty. The aetiology of dandruff is multifactorial, influenced by Malassezia, sebum production and individual susceptibility. The commensal yeast Malassezia is a strong contributory factor to dandruff formation, but the presence of Malassezia on healthy scalps indicates that Malassezia alone is not a sufficient cause. A healthy stratum corneum (SC) forms a protective barrier to prevent water loss and maintain hydration of the scalp. It also protects against external insults such as microorganisms, including Malassezia, and toxic materials. Severe or chronic barrier damage can impair proper hydration, leading to atypical epidermal proliferation, keratinocyte differentiation and SC maturation, which may underlie some dandruff symptoms. The depleted and disorganized structural lipids of the dandruff SC are consistent with the weakened barrier indicated by elevated transepidermal water loss. Further evidence of a weakened barrier in dandruff includes subclinical inflammation and higher susceptibility to topical irritants. We are proposing that disruption of the SC of the scalp may facilitate dandruff generation, in part by affecting susceptibility to metabolites from Malassezia. Treatment of dandruff with cosmetic products to directly improve SC integrity while providing effective antifungal activity may thus be beneficial. Résumé Les pellicules se caractérisent par un cuir chevelu prurigineux, squameux, et affectent jusqu’à la moitié de la population post-pubertaire du monde. L’étiologie des pellicules est multifactorielle, influencée par Malassezia, par la production de sébum, et par la susceptibilité individuelle. La levure commensale Malassezia est un facteur fortement contributif à la formation de pellicules, mais la présence de Malassezia aussi sur les cuirs chevelus sains indique que Malassezia seule n’est pas une cause

The global mechanical properties and multi-scale failure mechanics of heterogeneous human stratum corneum.

PubMed

Liu, X; Cleary, J; German, G K

2016-10-01

The outermost layer of skin, or stratum corneum, regulates water loss and protects underlying living tissue from environmental pathogens and insults. With cracking, chapping or the formation of exudative lesions, this functionality is lost. While stratum corneum exhibits well defined global mechanical properties, macroscopic mechanical testing techniques used to measure them ignore the structural heterogeneity of the tissue and cannot provide any mechanistic insight into tissue fracture. As such, a mechanistic understanding of failure in this soft tissue is lacking. This insight is critical to predicting fracture risk associated with age or disease. In this study, we first quantify previously unreported global mechanical properties of isolated stratum corneum including the Poisson's ratio and mechanical toughness. African American breast stratum corneum is used for all assessments. We show these parameters are highly dependent on the ambient humidity to which samples are equilibrated. A multi-scale investigation assessing the influence of structural heterogeneities on the microscale nucleation and propagation of cracks is then performed. At the mesoscale, spatially resolved equivalent strain fields within uniaxially stretched stratum corneum samples exhibit a striking heterogeneity, with localized peaks correlating closely with crack nucleation sites. Subsequent crack propagation pathways follow inherent topographical features in the tissue and lengthen with increased tissue hydration. At the microscale, intact corneocytes and polygonal shaped voids at crack interfaces highlight that cracks propagate in superficial cell layers primarily along intercellular junctions. Cellular fracture does occur however, but is uncommon. Human stratum corneum protects the body against harmful environmental pathogens and insults. Upon mechanical failure, this barrier function is lost. Previous studies characterizing the mechanics of stratum corneum have used macroscopic testing

Luliconazole Retention in Stratum Corneum and Prevention of Fungal Infection in a Guinea Pig Tinea Pedis Model.

PubMed

Koga, Hiroyasu; Nanjoh, Yasuko; Toga, Tetsuo; Pillai, Radhakrishnan; Jo, William; Tsuboi, Ryoji

2016-01-01

To compare drug concentrations in the stratum corneum following daily application of luliconazole and terbinafine cream in a guinea pig tinea pedis model. Luliconazole 1% cream or terbinafine 1% cream were topically applied once daily to hind limbs of guinea pigs for 14 days. Drug concentration in stratum corneum of plantar skin was measured by HPLC-UV on days 1, 3, 7, 10, and 14. Separately, creams were applied daily for 5 days to the hind limbs of guinea pigs and skin drug release determined. In addition, drug retention in the stratum corneum was assessed by infecting guinea pigs with Trichophyton mentagrophytes, 14 and 21 days after a single application of luliconazole or terbinafine creams. Luliconazole stratum corneum concentrations were higher than those of terbinafine throughout the study. Concentrations of luliconazole and terbinafine were 71.6μg/g and 36.6μg/g, respectively, after a single application (P<.05), reaching steady state after 10 days. Cumulative release of luliconazole from the stratum corneum was 4.5 times greater than with terbinafine. Unlike terbinafine, no fungal invasion of the stratum corneum was seen 14 days post-treatment with luliconazole. Drug concentrations of luliconazole in the stratum corneum and subsequent release are greater than those achieved with terbinafine and may contribute to clinical efficacy. Luliconazole may also provide greater protection against disease recurrence.

Presence and persistence of a highly ordered lipid phase state in the avian stratum corneum.

PubMed

Champagne, Alex M; Pigg, Victoria A; Allen, Heather C; Williams, Joseph B

2018-06-07

To survive high temperatures in a terrestrial environment, animals must effectively balance evaporative heat loss and water conservation. In passerine birds, cutaneous water loss (CWL) is the primary avenue of water loss at thermoneutral temperatures and increases slightly as ambient temperature increases, indicating a change in the permeability of the skin. In the stratum corneum (SC), the outermost layer of the skin, lipids arranged in layers called lamellae serve as the primary barrier to CWL in birds. The permeability of these lamellae depends in large part on the ability of lipid molecules to pack closely together in an ordered orthorhombic phase state. However, as temperature increases, lipids of the SC become more disordered, and may pack in more permeable hexagonal or liquid crystalline phase states. In this study, we used Fourier transform infrared spectroscopy to monitor the phase state of lipids in the SC of house sparrows ( Passer domesticus ) at skin temperatures ranging from 25 to 50°C. As temperature increased, lipids became slightly more disordered, but remained predominantly in the orthorhombic phase, consistent with the small increase in CWL observed in house sparrows as ambient temperature increases. These results differ considerably from studies on mammalian SC, which find a predominantly hexagonal arrangement of lipids at temperatures above 37°C, and the increased order in avian SC may be explained by longer lipid chain length, scarcity of cholesterol and the presence of cerebrosides. Our results lend further insight into the arrangement and packing of individual lipid molecules in avian SC. © 2018. Published by The Company of Biologists Ltd.

Concentration dependency in nicotine skin penetration flux from aqueous solutions reflects vehicle induced changes in nicotine stratum corneum retention.

PubMed

Kuswahyuning, Rina; Roberts, Michael S

2014-06-01

This study sought to understand the mechanism by which the steady state flux of nicotine across the human skin from aqueous solutions is markedly decreased at higher nicotine concentrations. Nicotine's steady state flux through human epidermis and its amount in the stratum corneum for a range of aqueous nicotine solutions was determined using Franz diffusion cells, with the nicotine analysed by high performance liquid chromatography (HPLC). Nicotine's thermodynamic activity in the various solutions was estimated from its partial vapour pressure and stratum corneum hydration was determined using a corneometer. The amount of nicotine retained in the stratum corneum was estimated from the nicotine amount found in individual stratum corneum tape strips and a D-Squame determined weight for each strip. The observed steady state flux of nicotine across human epidermis was found to show a parabolic dependence on nicotine concentration, with the flux proportional to its thermodynamic activity up to a concentration of 48% w/w. The nicotine retention in the stratum corneum showed a similar dependency on concentration whereas the diffusivity of nicotine in the stratum corneum appeared to be concentration independent. This retention, in turn, could be estimated from the extent of stratum corneum hydration and the nicotine concentration in the applied solution and volume of water in the skin. Nonlinear dependency of nicotine skin flux on its concentration results from a dehydration induced decrease in its stratum corneum retention at higher concentration and not dehydration induced changes nicotine diffusivity in the stratum corneum.

Reconstruction of stratum corneum profile of porcine ear skin after tape stripping using UV/VIS spectroscopy

NASA Astrophysics Data System (ADS)

Popov, Alexey P.; Lademann, Jürgen; Priezzhev, Alexander V.; Myllylä, Risto

2007-07-01

Stratum corneum (horny layer) is a superficial skin layer consisting of dead cells. To reveal in-depth penetration profiles of substances topically applied onto skin surface, a minimally invasive method called tape stripping is widely used. It introduces consecutive removal of micrometer-thick cell layers of stratum corneum from the same treated skin area using an adhesive tape. Prerequisite to the substance penetration profile is the reconstruction of the removed stratum corneum by analyzing the amount of corneocytes (cells of stratum corneum from) stuck to each tape strip. Before application in vivo on humans, porcine skin is often used for such kind of studies. In this paper, we present results of the experiments with porcine skin in vitro (ears of freshly slaughtered pigs) and compare them with those carried out on humans in vivo (flexor forearm) taken from references. As we proved experimentally, there is a linear dependence between the absorbance (equals to logarithm of inverse transmittance) and thickness of the corneocytes on tape strips for all wavelength of the investigated region (300-1050 nm). Dependence of the cumulative absorbance of removed stratum corneum on tape strip number can be satisfactory fitted by an exponential function. This relationship allows evaluation of the relative share of the removed stratum corneum without complete removal of the layer. All the obtained results correlate well with those obtained on humans.

Quantification of texture match of the skin graft: function and morphology of the stratum corneum.

PubMed

Inoue, K; Matsumoto, K

1986-01-01

In an attempt to analyze the "texture match" of grafted skin, functional and morphological aspects of the stratum corneum were studied using the Skin Surface Hydrometer (IBS Inc.) and the scanning electron microscope. The results showed that hygroscopicity and water holding capacity of the stratum corneum played a crucial role in making the skin surface soft and smooth. Morphologically there were regional differences in the surface pattern and the mean area of corneocytes, suggesting that these differences affect skin texture. It is suggested that the present functional and morphological studies of the stratum corneum can provide a quantitative measure of the "texture match".

Mechanics, morphology, and mobility in stratum corneum membranes

NASA Astrophysics Data System (ADS)

Olmsted, Peter; Das, Chinmay; Noro, Massimo

2012-02-01

The stratum corneum is the outermost layer of skin, and serves as a protective barrier against external agents, and to control moisture. It comprises keratin bodies (corneocytes) embedded in a matrix of lipid bilayers. Unlike the more widely studied phospholipid bilayers, the SC bilayers are typically in a gel-like state. Moreover, the SC membrane composition is radically different from more fluid counterparts: it comprises single tailed fatty acids, ceramides, and cholesterol; with many distinct ceramides possessing different lengths of tails, and always with two tails of different lengths. I will present insight from computer simulations into the morphology, mechanical properties, and diffusion (barrier) properties of these highly heterogeneous membranes. Our results provide some clue as to the design principles for the SC membrane, and is an excellent example of the use of wide polydispersity by natural systems.

Further investigations on the role of ascorbic acid in stratum corneum lipid models after UV exposure.

PubMed

Trommer, Hagen; Böttcher, Rolf; Huschka, Christoph; Wohlrab, Wolfgang; Neubert, Reinhard H H

2005-08-01

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.

A Coarse-grained Model of Stratum Corneum Lipids: Free Fatty Acids and Ceramide NS

PubMed Central

Moore, Timothy C.; Iacovella, Christopher R.; Hartkamp, Remco; Bunge, Annette L.; McCabe, Clare

2017-01-01

Ceramide (CER)-based biological membranes are used both experimentally and in simulations as simplified model systems of the skin barrier. Molecular dynamics studies have generally focused on simulating preassembled structures using atomistically detailed models of CERs, which limit the system sizes and timescales that can practically be probed, rendering them ineffective for studying particular phenomena, including self-assembly into bilayer and lamellar superstructures. Here, we report on the development of a coarse-grained (CG) model for CER NS, the most abundant CER in human stratum corneum. Multistate iterative Boltzmann inversion is used to derive the intermolecular pair potentials, resulting in a force field that is applicable over a range of state points and suitable for studying ceramide self-assembly. The chosen CG mapping, which includes explicit interaction sites for hydroxyl groups, captures the directional nature of hydrogen bonding and allows for accurate predictions of several key structural properties of CER NS bilayers. Simulated wetting experiments allow the hydrophobicity of CG beads to be accurately tuned to match atomistic wetting behavior, which affects the whole system since inaccurate hydrophobic character is found to unphysically alter the lipid packing in hydrated lamellar states. We find that CER NS can self-assemble into multilamellar structures, enabling the study of lipid systems more representative of the multilamellar lipid structures present in the skin barrier. The coarse-grained force field derived herein represents an important step in using molecular dynamics to study the human skin barrier, which gives a resolution not available through experiment alone. PMID:27564869

Sensitive skin and stratum corneum reactivity to household cleaning products.

PubMed

Goffin, V; Piérard-Franchimont, C; Piérard, G E

1996-02-01

Products intended for individuals with sensitive skin are being increasingly developed by formulators of household cleaning products. However, there is currently no consensus about the definition and recognition of the biological basis of sensitive skin. We sought to determine the relation between the nature of environmental threat perceived as aggressive by panelists, and the stratum corneum reactivity to household cleaning products as measured by the corneosurfametry test. Results indicate substantial differences in irritancy potential between proprietary products. Corneosurfametry data show significant differences in stratum corneum reactivity between, on the one hand, individuals with either non-sensitive skin or skin sensitive to climate/fabrics, and, on the other hand, individuals with detergent-sensitive skin. It is concluded that sensitive skin is not one single condition. Sound information in rating detergent-sensitive skin may be gained by corneosurfametry.

Electroperturbation of human stratum corneum fine structure by high voltage pulses: a freeze-fracture electron microscopy and differential thermal analysis study.

PubMed

Jadoul, A; Tanojo, H; Préat, V; Bouwstra, J A; Spies, F; Boddé, H E

1998-08-01

Application of high voltage pulses (HVP) to the skin has been shown to promote the transdermal drug delivery by a mechanism involving skin electroporation. The aim of this study was to detect potential changes in lipid phase and ultrastructure induced in human stratum corneum by various HVP protocols, using differential thermal analysis and freeze-fracture electron microscopy. Due to the time involved between the moment the electric field is switched off and the analysis, only "secondary" phenomena rather than primary events could be observed. A decrease in enthalpies for the phase transitions observed at 70 degrees C and 85 degrees C was detected by differential thermal analysis after HVP treatment. No changes in transition temperature could be seen. The freeze-fracture electron microscopy study revealed a dramatic perturbation of the lamellar ordering of the intercellular lipid after application of HVP. Most of the planes displayed rough surfaces. The lipid lamellae exhibited rounded off steps or a vanished stepwise order. There was no evidence for perturbation of the corneocytes content. In conclusion, the freeze-fracture electron microscopy and differential thermal analysis studies suggest that HVP application induces a general perturbation of the stratum corneum lipid ultrastructure.

Enhancement of skin radical scavenging activity and stratum corneum lipids after the application of a hyperforin-rich cream.

PubMed

Haag, S F; Tscherch, K; Arndt, S; Kleemann, A; Gersonde, I; Lademann, J; Rohn, S; Meinke, M C

2014-02-01

Hyperforin is well-known for its anti-inflammatory, anti-tumor, anti-bacterial, and antioxidant properties. The application of a hyperforin-rich verum cream could strengthen the skin barrier function by reducing radical formation and stabilizing stratum corneum lipids. Here, it was investigated whether topical treatment with a hyperforin-rich cream increases the radical protection of the skin during VIS/NIR irradiation. Skin lipid profile was investigated applying HPTLC on skin lipid extracts. Furthermore, the absorption- and scattering coefficients, which influence radical formation, were determined. 11 volunteers were included in this study. After a single cream application, VIS/NIR-induced radical formation could be completely inhibited by both verum and placebo showing an immediate protection. After an application period of 4weeks, radical formation could be significantly reduced by 45% following placebo application and 78% after verum application showing a long-term protection. Furthermore, the skin lipids in both verum and placebo groups increased directly after a single cream application but only significantly for ceramide [AP], [NP1], and squalene. After long-term cream application, concentration of cholesterol and the ceramides increased, but no significance was observed. These results indicate that regular application of the hyperforin-rich cream can reduce radical formation and can stabilize skin lipids, which are responsible for the barrier function. Copyright © 2013 Elsevier B.V. All rights reserved.

On the wetting properties of human stratum corneum epidermidis surface exposed to cold atmospheric-pressure pulsed plasma

NASA Astrophysics Data System (ADS)

Athanasopoulos, D.; Svarnas, P.; Ladas, S.; Kennou, S.; Koutsoukos, P.

2018-05-01

The Stratum corneum is the outermost layer of the skin, acting as a protective barrier of the epidermis, and its surface properties are directly related to the spreading of topically applied drugs and cosmetics. Numerous works have been devoted to the wettability of this layer over the past 70 years, but, despite the extensive application of atmospheric-pressure plasmas to dermatology, stratum corneum wettability with respect to plasma-induced species has never been considered. The present report assesses the treatment of human stratum corneum epidermidis by atmospheric-pressure pulsed cold plasma-jets for various time intervals and both chemical and morphological modifications are probed. The increase and saturation of the surface free energy due to functionalization are demonstrated, whereas prolonged treatment leads to tissue local disruption (tissue integrity is lost, and stratum corneum looks exfoliated, porous, and even thermally damaged). The latter point arises skepticism about the common practice of contacting atmospheric-pressure plasmas with skin without any previous precautions since the lost skin surface integrity may allow the penetration of pathogenic microorganisms.

Two randomized, controlled, comparative studies of the stratum corneum integrity benefits of two cosmetic niacinamide/glycerin body moisturizers vs. conventional body moisturizers.

PubMed

Christman, Jeremy C; Fix, Deborah K; Lucus, Sawanna C; Watson, Debrah; Desmier, Emma; Wilkerson, Rolanda J Johnson; Fixler, Charles

2012-01-01

Despite numerous body moisturizers being available, cosmetic xerosis continues to be a leading skin problem for consumers. We performed two 35-day studies to evaluate the ability of a variety of body moisturizers containing various levels of oils/lipids, humectants, as well as other ingredients (e.g., niacinamide) to improve stratum corneum integrity. 63 and 58 female subjects were enrolled and randomized in an incomplete block design to six of nine products (eight moisturizers or no treatment control) in studies 1 and 2, respectively. The primary endpoints included visual dryness by a qualified skin grader, skin hydration as measured by Corneometer, and barrier integrity as measured by transepidermal water loss (TEWL). The primary comparisons for the two niacinamide/glycerin moisturizers were to the other six moisturizers and to the no treatment control for each endpoint. The two niacinamide/glycerin moisturizers demonstrated an overall better solution towards rapid and prolonged improvement of cosmetic xerosis due to functional improvement of stratum corneum barrier function compared to no treatment and the other moisturizers tested. These studies establish the benefit of including niacinamide in a body moisturizer to improve the integrity of the stratum corneum and thus reduce cosmetic xerosis over time.

Stratum Corneum Lipids: Their Role for the Skin Barrier Function in Healthy Subjects and Atopic Dermatitis Patients.

PubMed

van Smeden, Jeroen; Bouwstra, Joke A

2016-01-01

Human skin acts as a primary barrier between the body and its environment. Crucial for this skin barrier function is the lipid matrix in the outermost layer of the skin, the stratum corneum (SC). Two of its functions are (1) to prevent excessive water loss through the epidermis and (2) to avoid that compounds from the environment permeate into the viable epidermal and dermal layers and thereby provoke an immune response. The composition of the SC lipid matrix is dominated by three lipid classes: cholesterol, free fatty acids and ceramides. These lipids adopt a highly ordered, 3-dimensional structure of stacked densely packed lipid layers (lipid lamellae): the lateral and lamellar lipid organization. The way in which these lipids are ordered depends on the composition of the lipids. One very common skin disease in which the SC lipid barrier is affected is atopic dermatitis (AD). This review addresses the SC lipid composition and organization in healthy skin, and elaborates on how these parameters are changed in lesional and nonlesional skin of AD patients. Concerning the lipid composition, the changes in the three main lipid classes and the importance of the carbon chain lengths of the lipids are discussed. In addition, this review addresses how these changes in lipid composition induce changes in lipid organization and subsequently correlate with an impaired skin barrier function in both lesional and nonlesional skin of these patients. Furthermore, the effect of filaggrin and mutations in the filaggrin gene on the SC lipid composition is critically discussed. Also, the breakdown products of filaggrin, the natural moisturizing factor molecules and its relation to SC-pH is described. Finally, the paper discusses some major changes in epidermal lipid biosynthesis in patients with AD and other related skin diseases, and how inflammation has a deteriorating effect on the SC lipids and SC biosynthesis. The review ends with perspectives on future studies in relation to

Thermodynamic Insights and Conceptual Design of Skin-Sensitive Chitosan Coated Ceramide/PLGA Nanodrug for Regeneration of Stratum Corneum on Atopic Dermatitis

PubMed Central

Jung, Sang-Myung; Yoon, Gwang Heum; Lee, Hoo Chul; Jung, Moon Hee; Yu, Sun Il; Yeon, Seung Ju; Min, Seul Ki; Kwon, Yeo Seon; Hwang, Jin Ha; Shin, Hwa Sung

2015-01-01

Atopic dermatitis (AD) is a complex skin disease primarily characterized by psoriasis of the stratum corneum. AD drugs have usually been used in acidic and hydrophilic solvents to supply moisture and prevent lipid defects. Ceramide is a typical treatment agent to regenerate the stratum corneum and relieve symptoms of AD. However, ceramide has limitation on direct use for skin because of its low dispersion properties in hydrophilic phase and side effects at excessive treatment. In this study, ceramide imbedded PLGA nanoparticles were developed with chitosan coating (Chi-PLGA/Cer) to overcome this problem. The chitosan coating enhanced initial adherence to the skin and prevented the initial burst of ceramide, but was degraded by the weakly acidic nature of skin, resulting in controlled release of ceramide with additional driving force of the squeezed PLGA nanoparticles. Additionally, the coating kinetics of chitosan were controlled by manipulating the reaction conditions and then mathematically modeled. The Chi-PLGA/Cer was not found to be cytotoxic and ceramide release was controlled by pH, temperature, and chitosan coating. Finally, Chi-PLGA/Cer was demonstrated to be effective at stratum corneum regeneration in a rat AD model. Overall, the results presented herein indicated that Chi-PLGA/Cer is a novel nanodrug for treatment of AD. PMID:26666701

Sensitive skin at menopause; dew point and electrometric properties of the stratum corneum.

PubMed

Paquet, F; Piérard-Franchimont, C; Fumal, I; Goffin, V; Paye, M; Piérard, G E

1998-01-12

A number of menopausal women experience skin sensitive to various environmental threats. Two panels of 15 menopausal women on or without HRT were compared. We studied the response of their stratum corneum to variations in environmental humidity, either in air or in response to an emollient. Environment dew point and electrometric measurements on the skin were recorded to search for correlations. Data show that the baseline stratum corneum hydration is influenced by the dew point. HRT improves the barrier function of the skin. The use of emollient further extends the improvement in the functional properties of skin in menopausal women. Both HRT and an emollient can counteract in part some of the deleterious effects of cold and dry weather.

Effect of chemical permeation enhancers on stratum corneum barrier lipid organizational structure and interferon alpha permeability.

PubMed

Moghadam, Shadi H; Saliaj, Evi; Wettig, Shawn D; Dong, Chilbert; Ivanova, Marina V; Huzil, J Torin; Foldvari, Marianna

2013-06-03

The outermost layer of the skin, known as the stratum corneum (SC), is composed of dead corneocytes embedded in an intercellular lipid matrix consisting of ceramides, free fatty acids, and cholesterol. The high level of organization within this matrix protects the body by limiting the permeation of most compounds through the skin. While essential for its protective functions, the SC poses a significant barrier for the delivery of topically applied pharmaceutical agents. Chemical permeation enhancers (CPEs) can increase delivery of small drug compounds into the skin by interacting with the intercellular lipids through physical processes including extraction, fluidization, increased disorder, and phase separation. However, it is not clear whether these same mechanisms are involved in delivery of biotherapeutic macromolecules, such as proteins. Here we describe the effect of three categories of CPEs {solvents [ethanol, propylene glycol, diethylene glycol monoethyl ether (transcutol), oleic acid], terpenes [menthol, nerol, camphor, methyl salicylate], and surfactants [Tween 80, SDS, benzalkonium chloride, polyoxyl 40 hydrogenated castor oil (Cremophor RH40), didecyldimethylammonium bromide (DDAB), didecyltrimethylammonium bromide (DTAB)]} on the lipid organizational structure of human SC as determined by X-ray scattering studies. Small- and wide-angle X-ray scattering studies were conducted to correlate the degree of structural changes and hydrocarbon chain packing in SC lipids caused by these various classes of CPEs to the extent of permeation of interferon alpha-2b (IFNα), a 19 kDa protein drug, into human skin. With the exception of solvents, propylene glycol and ethanol, all classes of CPEs caused increased disordering of lamellar and lateral packing of lipids. We observed that the highest degree of SC lipid disordering was caused by surfactants (especially SDS, DDAB, and DTAB) followed by terpenes, such as nerol. Interestingly, in vitro skin permeation studies

Molecular interactions of plant oil components with stratum corneum lipids correlate with clinical measures of skin barrier function

PubMed Central

Mack Correa, Mary Catherine; Mao, Guangru; Saad, Peter; Flach, Carol R; Mendelsohn, Richard; Walters, Russel M

2014-01-01

Plant-derived oils consisting of triglycerides and small amounts of free fatty acids (FFAs) are commonly used in skincare regimens. FFAs are known to disrupt skin barrier function. The objective of this study was to mechanistically study the effects of FFAs, triglycerides and their mixtures on skin barrier function. The effects of oleic acid (OA), glyceryl trioleate (GT) and OA/GT mixtures on skin barrier were assessed in vivo through measurement of transepidermal water loss (TEWL) and fluorescein dye penetration before and after a single application. OA's effects on stratum corneum (SC) lipid order in vivo were measured with infrared spectroscopy through application of perdeuterated OA (OA-d34). Studies of the interaction of OA and GT with skin lipids included imaging the distribution of OA-d34 and GT ex vivo with IR microspectroscopy and thermodynamic analysis of mixtures in aqueous monolayers. The oil mixtures increased both TEWL and fluorescein penetration 24 h after a single application in an OA dose-dependent manner, with the highest increase from treatment with pure OA. OA-d34 penetrated into skin and disordered SC lipids. Furthermore, the ex vivo IR imaging studies showed that OA-d34 permeated to the dermal/epidermal junction while GT remained in the SC. The monolayer experiments showed preferential interspecies interactions between OA and SC lipids, while the mixing between GT and SC lipids was not thermodynamically preferred. The FFA component of plant oils may disrupt skin barrier function. The affinity between plant oil components and SC lipids likely determines the extent of their penetration and clinically measurable effects on skin barrier functions. PMID:24372651

Developmental plasticity of cutaneous water loss and lipid composition in stratum corneum of desert and mesic nestling house sparrows

PubMed Central

Muñoz-Garcia, Agustí; Williams, Joseph B.

2008-01-01

Intercellular lipids of the stratum corneum (SC), the outer layer of the epidermis, form a barrier to water vapor diffusion through the skin. Previously, we measured cutaneous water loss (CWL) and lipid composition of the SC of adult house sparrows from two populations, one living in the deserts of Saudi Arabia and another living in mesic Ohio. Adult desert house sparrows had a lower CWL, a lower proportion of free fatty acids, and a higher proportion of ceramides and cerebrosides in the SC compared with mesic sparrows. In this study, we investigated developmental plasticity of CWL and lipid composition of the SC in desert and mesic nestling house sparrows reared in low and high humidity and compared our results with previous work on adults. We measured CWL of nestlings and analyzed the lipid composition of the SC using thin-layer chromatography. We showed that nestling house sparrows from both localities had higher CWL than adults in their natural environment, a result of major modifications of the lipid composition of the SC. The expression of plasticity in CWL seems to be a response to opposed selection pressures, thermoregulation and water conservation, at different life stages, on which regulation of CWL plays a crucial role. Desert nestlings showed a greater degree of plasticity in CWL and lipid composition of the SC than did mesic nestlings, a finding consistent with the idea that organisms exposed to more environmental stress ought to be more plastic than individuals living in more benign environments. PMID:18838693

Developmental plasticity of cutaneous water loss and lipid composition in stratum corneum of desert and mesic nestling house sparrows.

PubMed

Muñoz-Garcia, Agustí; Williams, Joseph B

2008-10-07

Intercellular lipids of the stratum corneum (SC), the outer layer of the epidermis, form a barrier to water vapor diffusion through the skin. Previously, we measured cutaneous water loss (CWL) and lipid composition of the SC of adult house sparrows from two populations, one living in the deserts of Saudi Arabia and another living in mesic Ohio. Adult desert house sparrows had a lower CWL, a lower proportion of free fatty acids, and a higher proportion of ceramides and cerebrosides in the SC compared with mesic sparrows. In this study, we investigated developmental plasticity of CWL and lipid composition of the SC in desert and mesic nestling house sparrows reared in low and high humidity and compared our results with previous work on adults. We measured CWL of nestlings and analyzed the lipid composition of the SC using thin-layer chromatography. We showed that nestling house sparrows from both localities had higher CWL than adults in their natural environment, a result of major modifications of the lipid composition of the SC. The expression of plasticity in CWL seems to be a response to opposed selection pressures, thermoregulation and water conservation, at different life stages, on which regulation of CWL plays a crucial role. Desert nestlings showed a greater degree of plasticity in CWL and lipid composition of the SC than did mesic nestlings, a finding consistent with the idea that organisms exposed to more environmental stress ought to be more plastic than individuals living in more benign environments.

Effect of menthone and related compounds on skin permeation of drugs with different lipophilicity and molecular organization of stratum corneum lipids.

PubMed

Lan, Yi; Wang, Jingyan; Li, Hui; Zhang, Yewen; Chen, Yanyan; Zhao, Bochen; Wu, Qing

2016-01-01

The objective of this article was to investigate the enhancing effect of menthone, menthol and pulegone on the transdermal absorption of drugs with different lipophilicity and probe their mechanisms of action at molecular level. Five model drugs, namely osthole, tetramethylpyrazine, ferulic acid, puerarin and geniposide, which were selected based on their lipophilicity denoted by logKo/w, were tested using in vitro permeation studies in which Franz diffusion cells and rat skin were employed. Infrared spectroscopy and molecular dynamic simulation were used to investigate the effect of these enhancers on the stratum corneum (SC) lipids, respectively. Three compounds could effectively promote the transdermal absorption of drugs with different lipophilicity, and the overall promoting capacities were in the following increasing order: pulegone < menthol < menthone. The penetration enhancement ratio was roughly in parabolic curve relationships with the drug lipophilicity after treatment with menthol or menthone, while the penetration enhancement effect of pulegone hardly changed with the alteration of the drug lipophilicity. The molecular mechanism studies suggested that menthone and menthol enhanced the skin permeability by disordering the ordered organization of SC lipids and extracted part of SC lipids, while pulegone appeared to promote drug transport across the skin only by extracting part of SC lipids.

The relationship between water loss, mechanical stress, and molecular structure of human stratum corneum ex vivo.

PubMed

Vyumvuhore, Raoul; Tfayli, Ali; Biniek, Krysta; Duplan, Hélène; Delalleau, Alexandre; Manfait, Michel; Dauskardt, Reinhold; Baillet-Guffroy, Arlette

2015-03-01

Proper hydration of the stratum corneum (SC) is important for maintaining skin's vital functions. Water loss causes development of drying stresses, which can be perceived as 'tightness', and plays an important role in dry skin damage processes. However, molecular structure modifications arising from water loss and the subsequent development of stress has not been established. We investigated the drying stress mechanism by studying, ex vivo, the behaviors of the SC components during water desorption from initially fully hydrated samples using Raman spectroscopy. Simultaneously, we measure the SC mechanical stress with a substrate curvature instrument. Very good correlations of water loss to the mechanical stress of the stratum corneum were obtained, and the latter was found to depend mainly on the unbound water fraction. In addition to that, the water loss is accompanied with an increase of lipids matrix compactness characterized by lower chain freedom, while protein structure showed an increase in amount of α-helices, a decline in α-sheets, and an increase in folding in the tertiary structure of keratin. The drying process of SC involves a complex interplay of water binding, molecular modifications, and mechanical stress. This article provides a better understanding of the molecular mechanism associated to SC mechanics. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of borneol on the transdermal permeation of drugs with differing lipophilicity and molecular organization of stratum corneum lipids.

PubMed

Yi, Qi-Feng; Yan, Jin; Tang, Si-Yuan; Huang, Hui; Kang, Li-Yang

2016-01-01

The aim of the present paper was to investigate the promoting activity of borneol on the transdermal permeation of drugs with differing lipophilicity, and probe its alterations in molecular organization of stratum corneum (SC) lipids. The toxicity of borneol was evaluated in epidermal keratinocyte HaCaT and dermal fibroblast CCC-HSF-1 cell cultures and compared to known enhancers, and its irritant profile was also assessed by transepidermal water loss (TEWL) evaluation. The promoting effect of borneol on the transdermal permeation of five model drugs, namely 5-fluorouracil, antipyrine, aspirin, salicylic acid and ibuprofen, which were selected based on their lipophilicity denoted by logp value, were performed using in vitro skin permeation studies. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) was employed to monitor the borneol-induced alteration in molecular organization of SC lipids. The enhancer borneol displayed lower cytotoxicity or irritation in comparison to the well-established and standard enhancer Azone. Borneol could effectively promote the transdermal permeation of five model drugs, and its enhancement ratios were found to be parabolic curve with the logp values of drugs, which exhibited the optimum permeation activity for relatively hydrophilic drugs (an estimated logp value of -0.5 ∼0.5). The molecular mechanism studies suggested that borneol could perturb the structure of SC lipid alkyl chains, and extract part of SC lipids, resulting in the alteration in the skin permeability barrier.

The Clinical Relevance of Maintaining the Functional Integrity of the Stratum Corneum in both Healthy and Disease-affected Skin

PubMed Central

Del Rosso, James Q.; Levin, Jacqueline

2011-01-01

It has been recognized for approximately 50 years that the stratum corneum exhibits biological properties that contribute directly to maintaining and sustaining healthy skin. Continued basic science and clinical research coupled with keen clinical observation has led to more recent recognition and general acceptance that the stratum corneum completes many vital “barrier” tasks, including but not limited to regulating epidermal water content and the magnitude of water loss; mitigating exogenous oxidants that can damage components of skin via an innate antioxidant system; preventing or limiting cutaneous infection via multiple antimicrobial peptides; responding via innate immune mechanisms to “cutaneous invaders” of many origins, including microbes, true allergens, and other antigens; and protecting its neighboring cutaneous cells and structures that lie beneath from damaging effects of ultraviolet radiation. Additionally, specific abnormalities of the stratum corneum are associated with the clinical expression of certain disease states. This article provides a thorough “primer” for the clinician, reviewing the multiple normal homeostatic functions of the stratum corneum and the cutaneous challenges that arise when individual functions of this thin yet very active epidermal layer are compromised by exogenous and/or endogenous factors. PMID:21938268

In vitro models to estimate drug penetration through the compromised stratum corneum barrier.

PubMed

Engesland, André; Škalko-Basnet, Nataša; Flaten, Gøril Eide

2016-11-01

The phospholipid vesicle-based permeation assay (PVPA) is a recently established in vitro stratum corneum model to estimate the permeability of intact and healthy skin. The aim here was to further evolve this model to mimic the stratum corneum in a compromised skin barrier by reducing the barrier functions in a controlled manner. To mimic compromised skin barriers, PVPA barriers were prepared with explicitly defined reduced barrier function and compared with literature data from both human and animal skin with compromised barrier properties. Caffeine, diclofenac sodium, chloramphenicol and the hydrophilic marker calcein were tested to compare the PVPA models with established models. The established PVPA models mimicking the stratum corneum in healthy skin showed good correlation with biological barriers by ranking drugs similar to those ranked by the pig ear skin model and were comparable to literature data on permeation through healthy human skin. The PVPA models provided reproducible and consistent results with a distinction between the barriers mimicking compromised and healthy skin. The trends in increasing drug permeation with an increasing degree of compromised barriers for the model drugs were similar to the literature data from other in vivo and in vitro models. The PVPA models have the potential to provide permeation predictions when investigating drugs or cosmeceuticals intended for various compromised skin conditions and can thus possibly reduce the time and cost of testing as well as the use of animal testing in the early development of drug candidates, drugs and cosmeceuticals.

Characterization of Skin Friction Coefficient, and Relationship to Stratum Corneum Hydration in a Normal Chinese Population

PubMed Central

Zhu, Y.H.; Song, S.P.; Luo, W.; Elias, P.M.; Man, M.Q.

2011-01-01

Background and Objectives Studies have demonstrated that some cutaneous biophysical properties vary with age, gender and body sites. However, the characteristics of the skin friction coefficient in different genders and age groups have not yet been well established. In the present study, we assess the skin friction coefficient in a larger Chinese population. Methods A total of 633 subjects (300 males and 333 females) aged 0.15–79 years were enrolled. A Frictiometer® FR 770 and Corneometer® CM 825 (C&K MPA 5) were used to measure the skin friction coefficient and stratum corneum hydration, respectively, on the dorsal surface of the hand, the forehead and the canthus. Results In the females, the maximum skin friction coefficients on both the canthus and the dorsal hand skin were observed around the age of 40 years. In the males, the skin friction coefficient on the dorsal hand skin gradually increased from 0 to 40 years of age, and changed little afterward. Skin friction coefficients on some body sites were higher in females than in age-matched males in some age groups. On the canthus and the dorsal hand skin of females, a positive correlation was found between skin friction coefficient and stratum corneum hydration (p < 0.001 and p < 0.0001, respectively). In contrast, in males, the skin friction coefficient was positively correlated with stratum corneum hydration on the forehead and the dorsal hand skin (p < 0.05 and p < 0.0001, respectively). Conclusion The skin friction coefficient varies with age, gender and body site, and positively correlates with stratum corneum hydration on some body sites. PMID:21088455

Characterization of skin friction coefficient, and relationship to stratum corneum hydration in a normal Chinese population.

PubMed

Zhu, Y H; Song, S P; Luo, W; Elias, P M; Man, M Q

2011-01-01

Studies have demonstrated that some cutaneous biophysical properties vary with age, gender and body sites. However, the characteristics of the skin friction coefficient in different genders and age groups have not yet been well established. In the present study, we assess the skin friction coefficient in a larger Chinese population. A total of 633 subjects (300 males and 333 females) aged 0.15-79 years were enrolled. A Frictiometer FR 770 and Corneometer CM 825 (C&K MPA 5) were used to measure the skin friction coefficient and stratum corneum hydration, respectively, on the dorsal surface of the hand, the forehead and the canthus. In the females, the maximum skin friction coefficients on both the canthus and the dorsal hand skin were observed around the age of 40 years. In the males, the skin friction coefficient on the dorsal hand skin gradually increased from 0 to 40 years of age, and changed little afterward. Skin friction coefficients on some body sites were higher in females than in age-matched males in some age groups. On the canthus and the dorsal hand skin of females, a positive correlation was found between skin friction coefficient and stratum corneum hydration (p < 0.001 and p < 0.0001, respectively). In contrast, in males, the skin friction coefficient was positively correlated with stratum corneum hydration on the forehead and the dorsal hand skin (p < 0.05 and p < 0.0001, respectively). The skin friction coefficient varies with age, gender and body site, and positively correlates with stratum corneum hydration on some body sites. Copyright © 2010 S. Karger AG, Basel.

Measurements of glucose on the skin surface, in stratum corneum and in transcutaneous extracts: implications for physiological sampling.

PubMed

Cunningham, David D; Young, Douglas F

2003-09-01

Obtaining representative physiological samples for glucose analysis remains a challenge especially when developing less invasive glucose monitoring systems for diabetic patients. In the present study the glucose content of the stratum corneum was compared with the amount of glucose obtained by short aqueous extractions from a site on the dorsal wrist, using high pressure liquid chromatography with pulsed amperometric detection. Ten successive aqueous 1-minute extractions of the site yielded a total of 60 ng cm(-2). The total glucose content of the stratum corneum of the site, determined from 30 successive tape-strippings of the site, was 360 ng cm(-2). After tape-stripping, the transcutaneous aqueous extraction rate was 86 +/- 13 ng cm(-2) min(-1), compared with rates of 80-600 ng cm(-2) min(-1) obtained with suction effusion or microdialysis after tape-stripping. Glucose on the surface of the skin and within the stratum corneum should be considered as sources of extraneous glucose contamination during testing of less invasive glucose monitoring devices.

Removal of adhesive wound dressing and its effects on the stratum corneum of the skin: comparison of eight different adhesive wound dressings.

PubMed

Matsumura, Hajime; Imai, Ryutaro; Ahmatjan, Niyaz; Ida, Yukiko; Gondo, Masahide; Shibata, Dai; Wanatabe, Katsueki

2014-02-01

In recent years, adhesive wound dressings have been increasingly applied postoperatively because of their ease of use as they can be kept in place without having to cut and apply surgical tapes and they can cover a wound securely. However, if a wound dressing strongly adheres to the wound, a large amount of stratum corneum is removed from the newly formed epithelium or healthy periwound skin. Various types of adhesives are used on adhesive wound dressings and the extent of skin damage depends on how much an adhesive sticks to the wound or skin surface. We quantitatively determined and compared the amount of stratum corneum removed by eight different wound dressings including polyurethane foam using acrylic adhesive, silicone-based adhesive dressing, composite hydrocolloid and self-adhesive polyurethane foam in healthy volunteers. The results showed that wound dressings with silicone adhesive and self-adhesive polyurethane foam removed less stratum corneum, whereas composite hydrocolloid and polyurethane foam using acrylic adhesive removed more stratum corneum. © 2012 The Authors. International Wound Journal © 2012 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Usefulness of pressure-sensitive adhesives as a pretreatment material before application of topical drug formulations and a peeling tape for excess stratum corneum layers.

PubMed

Kikuchi, Keisuke; Todo, Hiroaki; Sugibayashi, Kenji

2014-01-01

Two unique pressure-sensitive adhesive (PSA) tapes (PSA-A, -B) with different adhesive properties of commercial PSAs were prepared and evaluated for their usefulness as a pretreatment material prior to the application of transdermal therapeutic systems or topical drug formulations and also as a peeling agent against excess layers of the stratum corneum. In the present study, in vitro permeation experiments were conducted using vertical type diffusion cells and excised hairless rat or porcine skin from which the stratum corneum had been stripped several times with PSAs. The results obtained revealed that PSA-A and -B had higher stripping or peeling effects than those of the marketed PSAs. Marked changes were observed in skin barrier function before and after stripping using PSAs, and the enhancement effect on the skin permeation of drugs achieved by stripping the stratum corneum was markedly different between the PSAs. PSA-A, in particular, markedly improved skin permeation and the skin concentration of topically applied chemical compounds because it removed many layers of the stratum corneum when skin was stripped only a few times. In contrast, when PSA-B was used to pretreat the skin surface, the extent of skin permeation and concentration of drugs was safely increased because only a few layers of the stratum corneum were removed, even with repeated stripping. The enhancement effect achieved by PSA-B was not as high as that by PSA-A. Thus, stripping with PSA-A can be used as a penetration enhancement tool, whereas PSA-B can be used as a peeling material against excess layers of the stratum corneum.

Mathematical Description of the Uptake of Hydrocarbons in Jet Fuel into the Stratum Corneum of Human Volunteers

PubMed Central

Kim, David; Farthing, Matthew W.; Miller, Cass T.; Nylander-French, Leena A.

2008-01-01

The objective of this research was to develop a mathematical description of uptake of aromatic and aliphatic hydrocarbons into the stratum corneum of human skin in vivo. A simple description based on Fick’s Laws of diffusion was used to predict the spatiotemporal variation of naphthalene, 1- and 2-methylnaphthalene, undecane, and dodecane in the stratum corneum of human volunteers. The estimated values of the diffusion coefficients for each chemical were comparable to values predicted using in vitro skin systems and biomonitoring studies. These results demonstrate the value of measuring dermal exposure using the tape-strip technique and the importance of quantifying of dermal uptake. PMID:18423910

Non-invasive quantification of melanin in the stratum corneum: a novel indicator of skin lesions in pigmentation diseases.

PubMed

Matsunaka, H; Yamamoto, Y; Furukawa, F

2017-02-01

Skin melanin content is an important indicator for ascertaining the pathology of skin pigmentation diseases, but its analysis necessitates a biopsy or other means of collecting tissue, posing a considerable burden to the patient, and making it difficult to observe how a given skin site changes over time. Here, we aimed to establish a non-invasive method for quantifying the eumelanin and pheomelanin content of the stratum corneum. Sun-exposed and non-exposed samples from 10 healthy Japanese subjects were compared. We harvested the outermost layer of the stratum corneum by tape-stripping, considering the outer side of the forearm as a sun-exposed area, and medial side of the upper arm as a non-exposed area. Four additional subjects were included in the analysis of change in melanin content over time at the same skin site. The anterior lower leg received a single exposure to two minimal erythema dose sunlight, and the stratum corneum was harvested from the same site over a period of 20 weeks; we subsequently quantified the levels of eumelanin and pheomelanin using high-performance liquid chromatography. We were able to accurately quantify the eumelanin and pheomelanin contents of the stratum corneum, and to observe the evolution of the same skin site over time. Eumelanin levels were significantly higher in the sun-exposed area, with a peak in melanin observed after 11-15 weeks of sun exposure. This non-invasive method can serve as a marker for pathology of skin pigmentation diseases such as malignant tumors. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Vehicle effects on human stratum corneum absorption and skin penetration.

PubMed

Zhang, Alissa; Jung, Eui-Chang; Zhu, Hanjiang; Zou, Ying; Hui, Xiaoying; Maibach, Howard

2017-05-01

This study evaluated the effects of three vehicles-ethanol (EtOH), isopropyl alcohol (IPA), and isopropyl myristate (IPM)-on stratum corneum (SC) absorption and diffusion of the [ 14 C]-model compounds benzoic acid and butenafine hydrochloride to better understand the transport pathways of chemicals passing through and resident in SC. Following application of topical formulations to human dermatomed skin for 30 min, penetration flux was observed for 24 h post dosing, using an in vitro flow-through skin diffusion system. Skin absorption and penetration was compared to the chemical-SC (intact, delipidized, or SC lipid film) binding levels. A significant vehicle effect was observed for chemical skin penetration and SC absorption. IPA resulted in the greatest levels of intact SC/SC lipid absorption, skin penetration, and total skin absorption/penetration of benzoic acid, followed by IPM and EtOH, respectively. For intact SC absorption and total skin absorption/penetration of butenafine, the vehicle that demonstrated the highest level of sorption/penetration was EtOH, followed by IPA and IPM, respectively. The percent doses of butenafine that were absorbed in SC lipid film and penetrated through skin in 24 h were greatest for IPA, followed by EtOH and IPM, respectively. The vehicle effect was consistent between intact SC absorption and total chemical skin absorption and penetration, as well as SC lipid absorption and chemical penetration through skin, suggesting intercellular transport as a main pathway of skin penetration for model chemicals. These results suggest the potential to predict vehicle effects on skin permeability with simple SC absorption assays. As decontamination was applied 30 min after chemical exposure, significant vehicle effects on chemical SC partitioning and percutaneous penetration also suggest that skin decontamination efficiency is vehicle dependent, and an effective decontamination method should act on chemical solutes in the lipid domain.

Evaluation of the molecular lipid organization in millimeter-sized stratum corneum by synchrotron X-ray diffraction.

PubMed

Suzuki, T; Uchino, T; Hatta, I; Miyazaki, Y; Kato, S; Sasaki, K; Kagawa, Y

2018-04-29

The aim of this study was to investigate whether the lamellar and lateral structure of intercellular lipid of stratum corneum (SC) can be evaluated from millimeter-sized SC (MSC) by X-ray diffraction. A 12 mm × 12 mm SC sheet from hairless mouse was divided into 16 pieces measuring 3 mm × 3 mm square. From another sheet, 4 pieces of ultramillimeter-sized SC (USC:1.5 mm × 1.5 mm square) were prepared. Small and wide-angle X-ray diffraction (SAXD and WAXD) measurements were performed on each piece. For MSC and USC, changes in the lamellar and lateral structure after the application of d-limonene were measured. The intensity of SAXD peaks due to the lamellar phase of long periodicity phase (LPP) and WAXD peaks due to the lateral hydrocarbon chain-packing structures varied in MSC and USC pieces, although over the 12 mm × 12 mm SC sheet. These results indicated that the intercellular lipid components and their proportion appeared nearly uniform. Application of d-limonene on MSC and USC piece with strong peaks in SAXD and the WAXD resulted in the disappearance of peaks due to the lamellar phase of LPP and decrease in peak intensity for the lateral hydrocarbon chain-packing structures. These changes are consistent with normal-sized sample results. We found that the selection of a sample piece with strong diffraction peaks due to the lamellar and lateral structure enabled evaluation of the SC structure in small-sized samples by X-ray diffraction. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Influence of DMPS on the water retention capacity of electroporated stratum corneum: ATR-FTIR study.

PubMed

Sckolnick, Maria; Hui, Sek-Wen; Sen, Arindam

2008-02-28

Anionic lipids like phosphatidylserine are known to significantly enhance electroporation mediated transepidermal transport of polar solutes of molecular weights up to 10kDa. The underlying mechanism of the effect of anionic lipids on transdermal transport is not fully understood. The main barrier to transdermal transport lies within the intercellular lipid matrix (ILM) of the stratum corneum (SC) and our previous studies indicate that dimyristoyl phosphatidylserine (DMPS) can perturb the packing of this lipid matrix. Here we report on our investigation on water retention in the SC following electroporation in the presence and the absence of DMPS. The water content in the outer most layers of the SC of full thickness porcine skin was determined using ATR-FTIR-spectroscopy. The results show that in the presence of DMPS, the SC remains in a state of enhanced hydration for longer periods after electroporation. This increase in water retention in the SC by DMPS is likely to play an important role in trans-epidermal transport, since improved hydration of the skin barrier can be expected to increase the partitioning of polar solutes and possibly the permeability.

Cutaneous water loss and covalently bound lipids of the stratum corneum in nestling house sparrows (Passer domesticus L.) from desert and mesic habitats.

PubMed

Clement, Michelle E; Muñoz-Garcia, Agustí; Williams, Joseph B

2012-04-01

Lipids of the stratum corneum (SC), the outer layer of the epidermis of birds and mammals, provide a barrier to water vapor diffusion through the skin. The SC of birds consists of flat dead cells, called corneocytes, and two lipid compartments: an intercellular matrix and a monolayer of covalently bound lipids (CBLs) attached to the outer surface of the corneocytes. We previously found two classes of sphingolipids, ceramides and cerebrosides, covalently bound to corneocytes in the SC of house sparrows (Passer domesticus L.); these lipids were associated with cutaneous water loss (CWL). In this study, we collected adult and nestling house sparrows from Ohio and nestlings from Saudi Arabia, acclimated them to either high or low humidity, and measured their rates of CWL. We also measured CWL for natural populations of nestlings from Ohio and Saudi Arabia, beginning when chicks were 2 days old until they fledged. We then evaluated the composition of the CBLs of the SC of sparrows using thin layer chromatography. We found that adult house sparrows had a greater diversity of CBLs in their SC than previously described. During ontogeny, nestling sparrows increased the amount of CBLs and developed their CBLs differently, depending on their habitat. Acclimating nestlings to different humidity regimes did not alter the ontogeny of the CBLs, suggesting that these lipids represent a fundamental component of SC organization that does not respond to short-term environmental change.

Terahertz wave techniques using a metal mesh for evaluating the components of the stratum corneum.

PubMed

Mizukoshi, Koji; Yonekura, Kazuki; Ogura, Hidehiro; Guan, Yu; Kawase, Kodo

2013-02-01

Terahertz waves are located in the region of the spectrum between milliwaves and infrared. We analyzed the feasibility of terahertz spectroscopy to inspect the compositional variations of the stratum corneum (SC). We used a terahertz time-domain spectroscopy system with the metal mesh technique. To investigate whether terahertz can inspect compositional variation of SC, we measured the terahertz frequency spectra of the SC sheet that was treated with chloroform-methanol, lipid mixture, a denaturation agent, and heating with hot air. The chloroform-methanol treatment of the SC shifted the dip position, which represents a convex downward shape of the spectra, to a higher frequency. This dip shift was reversed to an untreated position by the dose-dependent application of a lipid mixture. The heating treatment of the SC shifted the dip position to a higher frequency. The same dip shift was also induced by the application of a denaturation agent to the SC. The technique using terahertz waves with a metal mesh is effective because of its simplicity and its high degree of accuracy in detecting the amount of lipid and the protein conformation state. © 2012 John Wiley & Sons A/S.

Induction of a Hardening Phenomenon and Quantitative Changes of Ceramides in Stratum Corneum

PubMed Central

Park, Sook Young; Kim, Jin Hye; Cho, Soo Ick; Kim, Kyeong Il; Cho, Hee Jin; Park, Chun Wook; Lee, Cheol Heon

2014-01-01

Background Hardening phenomenon of human skin after repeated exposure to the irritants is well-known, but the precise mechanism remains elusive. Objective To modify the previous experimental model of hardening phenomenon by repeated applications of two different concentrations of sodium lauryl sulfate (SLS) solutions to Korean healthy volunteers and to investigate the quantitative changes of ceramides in stratum corneum before and after chronic repeated irritation. Methods Eight hundred microliters of distilled water containing 0.1% and 2% SLS was applied for 10 minutes on the forearm of 41 healthy volunteers for 3 weeks. After an intervening 3-week rest, 24-hour patch tests with 1% SLS were conducted on previously irritated sites. Transepidermal water loss (TEWL), erythema index and quantity of ceramide were measured in the stratum corneum before and after irritation. Results TEWL values on the sites preirritated with 2% SLS were lower than those with 0.1% SLS. Hardening phenomenon occurred in 24 volunteers at day 44. The changes in ceramide levels were not significantly higher in the hardened skin than in the non-hardened skin. Conclusion Repetitive stimulation with a higher concentration of SLS can more easily trigger skin hardening. PMID:24648684

A mechanistic insight into the mechanical role of the stratum corneum during stretching and compression of the skin.

PubMed

Leyva-Mendivil, Maria F; Page, Anton; Bressloff, Neil W; Limbert, Georges

2015-09-01

The study of skin biophysics has largely been driven by consumer goods, biomedical and cosmetic industries which aim to design products that efficiently interact with the skin and/or modify its biophysical properties for health or cosmetic benefits. The skin is a hierarchical biological structure featuring several layers with their own distinct geometry and mechanical properties. Up to now, no computational models of the skin have simultaneously accounted for these geometrical and material characteristics to study their complex biomechanical interactions under particular macroscopic deformation modes. The goal of this study was, therefore, to develop a robust methodology combining histological sections of human skin, image-processing and finite element techniques to address fundamental questions about skin mechanics and, more particularly, about how macroscopic strains are transmitted and modulated through the epidermis and dermis. The work hypothesis was that, as skin deforms under macroscopic loads, the stratum corneum does not experience significant strains but rather folds/unfolds during skin extension/compression. A sample of fresh human mid-back skin was processed for wax histology. Sections were stained and photographed by optical microscopy. The multiple images were stitched together to produce a larger region of interest and segmented to extract the geometry of the stratum corneum, viable epidermis and dermis. From the segmented structures a 2D finite element mesh of the skin composite model was created and geometrically non-linear plane-strain finite element analyses were conducted to study the sensitivity of the model to variations in mechanical properties. The hybrid experimental-computational methodology has offered valuable insights into the simulated mechanics of the skin, and that of the stratum corneum in particular, by providing qualitative and quantitative information on strain magnitude and distribution. Through a complex non-linear interplay

In vivo penetration of bare and lipid-coated silica nanoparticles across the human stratum corneum.

PubMed

Iannuccelli, Valentina; Bertelli, Davide; Romagnoli, Marcello; Scalia, Santo; Maretti, Eleonora; Sacchetti, Francesca; Leo, Eliana

2014-10-01

Skin penetration of silica nanoparticles (NP) currently used in pharmaceutical and cosmetic products is a topic of interest not only to evaluate their possible toxicity, but also to understand their behaviour upon contact with the skin and to exploit their potential positive effects in drug or cosmetic delivery field. Therefore, the present work aimed to elucidate the in vivo mechanism by which amorphous hydrophilic silica NP enter human stratum corneum (SC) through the evaluation of the role played by the nanoparticle surface polarity and the human hair follicle density. Two silica samples, bare hydrophilic silica (B-silica, 162±51nm in size) and hydrophobic lipid-coated silica (LC-silica, 363±74nm in size) were applied on both the volar and dorsal side of volunteer forearms. Twelve repetitive stripped tapes were removed from the human skin and evaluated for elemental composition by Energy Dispersive X-ray (EDX) analysis and for silicon content by Inductively Coupled Plasma quadrupole Mass Spectrometry (ICP-MS). All the stripped tapes revealed nanosized structures generally located in the broad spaces between corneocytes and characterized by the same elemental composition (relative weight percentage of silicon and silicon to oxygen weight ratio) than that of the applied samples. However, only about 10% B-silica permeated until the deepest SC layers considered in the study indicating a silica retention in the upper layers of SC, regardless of the hair follicle density. Otherwise, the exposure to LC-silica led to a greater silica skin penetration extent into the deeper SC layers (about 42% and 18% silica following volar and dorsal forearm application, respectively) indicating that the NP surface polarity played a predominant role on that of their size in determining the route and the extent of penetration. Copyright © 2014 Elsevier B.V. All rights reserved.

Two dimensional finite element modelling for dynamic water diffusion through stratum corneum.

PubMed

Xiao, Perry; Imhof, Robert E

2012-10-01

Solvents penetration through in vivo human stratum corneum (SC) has always been an interesting research area for trans-dermal drug delivery studies, and the importance of intercellular routes (diffuse in between corneocytes) and transcellular routes (diffuse through corneocytes) during diffusion is often debatable. In this paper, we have developed a two dimensional finite element model to simulate the dynamic water diffusion through the SC. It is based on the brick-and-mortar model, with brick represents corneocytes and mortar represents lipids, respectively. It simulates the dynamic water diffusion process through the SC from pre-defined initial conditions and boundary conditions. Although the simulation is based on water diffusions, the principles can also be applied to the diffusions of other topical applied substances. The simulation results show that both intercellular routes and transcellular routes are important for water diffusion. Although intercellular routes have higher flux rates, most of the water still diffuse through transcellular routes because of the high cross area ratio of corneocytes and lipids. The diffusion water flux, or trans-epidermal water loss (TEWL), is reversely proportional to corneocyte size, i.e. the larger the corneocyte size, the lower the TEWL, and vice versa. There is also an effect of the SC thickness, external air conditions and diffusion coefficients on the water diffusion through SC on the resulting TEWL. Copyright © 2012 Elsevier B.V. All rights reserved.

Comparison of gravimetric and spectroscopic approaches to quantify stratum corneum removed by tape-stripping.

PubMed

Mohammed, D; Yang, Q; Guy, R H; Matts, P J; Hadgraft, J; Lane, M E

2012-09-01

Skin surface tape-stripping is an extensively used technique to examine the distribution profile, penetration and safety of various active compounds. It is also a widely accepted method to probe skin barrier properties and more specifically, those of the stratum corneum (SC). The amount of SC removed by tape-stripping is generally determined either gravimetrically or by extraction and measurement of SC proteins. A novel infra-red densitometry (IRD) technique has recently been introduced to measure SC protein content. In the present study, IRD was investigated as an alternative method to measure the mass of SC removed by tape-stripping. Tape-stripping experiments were conducted on human volunteers. The weight of the stratum corneum removed was assessed by the gravimetric approach and by IRD. Transepidermal water loss (TEWL) was also measured before and after each tape-strip. A linear correlation coefficient was obtained for the data from the gravimetric and IRD measurements (r(2)=0.65; n=240). IRD is therefore proposed as a rapid, non-destructive alternative to the gravimetric approach to estimate the amount of SC removed by tape-stripping in vivo. Copyright © 2012 Elsevier B.V. All rights reserved.

Evaluation of the effect of zinc acetate on the stratum corneum penetration kinetics of erythromycin in healthy male volunteers.

PubMed

van Hoogdalem, E J; Terpstra, I J; Baven, A L

1996-01-01

Erythromycin with or without additional zinc acetate is used topically in the treatment of acne vulgaris. A potential effect of zinc on the stratum corneum penetration of erythromycin was investigated in human volunteers. Skin surface washings and tape strippings from the skin of the back were collected after drug applications in 12 subjects for quantification of erythromycin levels. Zinc acetate increased the amount remaining on the back skin at 6 h after application from 40 +/- 19 to 56 +/- 15% of the dose and, vice versa, reduced the amount in stratum corneum strips from 22 +/- 7 to 18 +/- 7%, both with statistical significance. The effect varied with body region. Zinc acetate thus provided to prolong the residence time of erythromycin on the skin.

[Impact of wet work on epidermal barrier (tewl and stratum corneum hydration) and skin viscoelasticity in nurses].

PubMed

Kieć-Świcrczyńska, Marta; Chomiczewska-Skóra, Dorota; Świerczyńska-Machura, Dominika; Kręcisz, Beata

2014-01-01

Nurses are prone to develop hand eczema due to occupational exposure to irritants, including wet work. The aim of the study was to evaluate the impact of wet work on selected skin properties, reflecting epidermal barrier function--transepidermal water loss (TEWL) and stratum corneum hydration--and additionally skin viscoelasticity, in nurses. Study subjects included 90 nurses employed in hospital wards. Measurements were carried out within the dorsal aspect of the dominant hand, using a Cutometer MPA 580 equipped with Tewameter TM 300 and Corneometer CM 825 (Courage & Khazaka, Germany) probes. Examina- tions took place on hospital premises. Similar measurements were performed in the control group of females non-exposed to irritants. In the examined group of nurses, mean TEWL was 15.5 g/h/m2 and was higher than in the control group (12.99 g/h/m2). After rejecting the extreme results, the difference between the groups proved to be statistically significant (p < 0.05). The mean value of stratum corneum hydration was lower in the examined group (37.915) compared with the control group (40.05), but the difference was not sta tistically significant. Also results of viscoelasticity assessment showed no significant differences between studied groups. The results of the assessment of skin biophysical properties show that wet work exerts a moderately adverse impact on skin condition. A higher TEWL value and a lower stratum corneum hydration in workers exposed to irritants reflect an adverse impact of these factors on the epidermal barrier function.

Stratum corneum hydration and skin surface pH in patients with atopic dermatitis.

PubMed

Knor, Tanja; Meholjić-Fetahović, Ajša; Mehmedagić, Aida

2011-01-01

Atopic dermatitis (AD) is a chronically relapsing skin disease with genetic predisposition, which occurs most frequently in preschool children. It is considered that dryness and pruritus, which are always present in AD, are in correlation with degradation of the skin barrier function. Measurement of hydration and pH value of the stratum corneum is one of the noninvasive methods for evaluation of skin barrier function. The aim of the study was to assess skin barrier function by measuring stratum corneum hydration and skin surface pH of the skin with lesions, perilesional skin and uninvolved skin in AD patients, and skin in a healthy control group. Forty-two patients were included in the study: 21 young and adult AD patients and 21 age-matched healthy controls. Capacitance, which is correlated with hydration of stratum corneum and skin surface pH were measured on the forearm in the above areas by SM810/CM820/pH900 combined units (Courage AND Khazaka, Germany). The mean value of water capacitance measured in AD patients was 44.1 ± 11.6 AU (arbitrary units) on the lesions, 60.2 ± 12.4 AU on perilesional skin and 67.2 ± 8.8 AU on uninvolved skin. In healthy controls, the mean value was 74.1 ± 9.2 AU. The mean pH value measured in AD patients was 6.13 ± 0.52 on the lesions, 5.80 ± 0.41 on perilesional skin, and 5.54 ± 0.49 on uninvolved skin. In control group, the mean pH of the skin surface was 5.24 ± 0.40. The values of both parameters measured on lesional skin were significantly different (capacitance decreased and pH increased) from the values recorded on perilesional skin and uninvolved skin. The same held for the relation between perilesional and uninvolved skin. According to study results, the uninvolved skin of AD patients had significantly worse values of the measured parameters as compared with control group. The results of this study suggested the skin barrier function to be degraded in AD patients, which is specifically expressed in lesional skin.

Non steady-state descriptions of drug permeation through stratum corneum. I. The biphasic brick-and-mortar model.

PubMed

Heisig, M; Lieckfeldt, R; Wittum, G; Mazurkevich, G; Lee, G

1996-03-01

The diffusion equation should be solved for the non-steady-state problem of drug diffusion within a two-dimensional, biphasic stratum corneum membrane having homogeneous lipid and corneocyte phases. A numerical method was developed for a brick-and-mortar SC-geometry, enabling an explicit solution for time-dependent drug concentration within both phases. The lag time and permeability were calculated. It is shown how the barrier property of this model membrane depends on relative phase permeability, corneocyte alignment, and corneocyte-lipid partition coefficient. Additionally, the time-dependent drug concentration profiles within the membrane can be observed during the lag and steady-state phases. The model SC-membrane predicts, from purely morphological principles, lag times and permeabilities that are in good agreement with experimental values. The long lag times and very small permeabilities reported for human SC can only be predicted for a highly-staggered corneocyte geometry and corneocytes that are 1000 times less permeable than the lipid phase. Although the former conclusion is reasonable, the latter is questionable. The elongated, flattened corneocyte shape renders lag time and permeability insensitive to large changes in their alignment within the SC. Corneocyte/lipid partitioning is found to be fundamentally different to SC/donor partitioning, since increasing drug lipophilicity always reduces both lag time and permeability.

From observational to analytical morphology of the stratum corneum: progress avoiding hazardous animal and human testings

PubMed Central

Piérard, Gérald E; Courtois, Justine; Ritacco, Caroline; Humbert, Philippe; Fanian, Ferial; Piérard-Franchimont, Claudine

2015-01-01

Background In cosmetic science, noninvasive sampling of the upper part of the stratum corneum is conveniently performed using strippings with adhesive-coated discs (SACD) and cyanoacrylate skin surface strippings (CSSSs). Methods Under controlled conditions, it is possible to scrutinize SACD and CSSS with objectivity using appropriate methods of analytical morphology. These procedures apply to a series of clinical conditions including xerosis grading, comedometry, corneodynamics, corneomelametry, corneosurfametry, corneoxenometry, and dandruff assessment. Results With any of the analytical evaluations, SACD and CSSS provide specific salient information that is useful in the field of cosmetology. In particular, both methods appear valuable and complementary in assessing the human skin compatibility of personal skincare products. Conclusion A set of quantitative analytical methods applicable to the minimally invasive and low-cost SACD and CSSS procedures allow for a sound assessment of cosmetic effects on the stratum corneum. Under regular conditions, both methods are painless and do not induce adverse events. Globally, CSSS appears more precise and informative than the regular SACD stripping. PMID:25767402

Permeabilization and recovery of the stratum corneum in vivo: the synergy of photomechanical waves and sodium lauryl sulfate.

PubMed

Lee, S; McAuliffe, D J; Kollias, N; Flotte, T J; Doukas, A G

2001-01-01

Photomechanical waves render the stratum corneum permeable and allow macromolecules to diffuse into the epidermis and dermis. The aim of this study was to investigate the combined action of photomechanical waves and sodium lauryl sulfate, an anionic surfactant, for transdermal delivery. A single photomechanical wave was applied to the skin of rats in the presence of sodium lauryl sulfate. The sodium lauryl sulfate solution was removed and aqueous solutions of rhodamine-B dextran (40 kDa molecular weight) were applied to the skin at time points 2, 30, and 60 minutes post-exposure. The presence of rhodamine-B dextran in the skin was measured by fluorescence emission spectroscopy in vivo and fluorescence microscopy of frozen biopsies. The use of sodium lauryl sulfate delayed the recovery of the stratum corneum barrier and extended the time available for the diffusion of dextran through it. The combination of photomechanical waves and surfactants can enhance transdermal drug delivery. Copyright 2001 Wiley-Liss, Inc.

Leaching from the stratum corneum does not explain the previously reported elevated potassium ion concentration in sweat.

PubMed

Buono, Michael J; Stone, Michael; Cannon, Daniel T

2016-03-01

The purpose of this study was to determine if K+ is leached from the stratum corneum when sweat is present on the skin's surface. The results will help address whether sweat [K+] previously reported in the literature are artifactually elevated as a result of K+ leaching. Twelve (six female, six male) healthy volunteers participated in this study. After thorough skin cleansing and preparation with isopropyl alcohol and high-performance liquid chromatography-grade distilled water, three sites were chosen and a 50 μL drop of artificial sweat was pipetted directly onto the skin. The artificial sweat had a [K+] of 4 mEq·L-1, an osmolality of 120 mosm·L-1, and a pH of 6.0. Immediately following, a clear plastic cover slip (~6 cm2) with a shallow 0.8 cm2 convex impression in the center was applied over each drop, preventing evaporation. Each sample was allowed to sit on the forearm, under the plastic cover slip, for 10 min. The mean (±SD) [K+] in 'artificial' sweat not exposed to the skin was measured to be 4.2±0.4 mEq·L-1. After 10 min of exposure to the stratum corneum of the forearm, the artificial sweat had a mean (±SD) [K+] of 3.9±0.3 mEq·L-1. There was no significant difference (p>0.05) in the [K+] between the control artificial sweat and the samples collected after 10 min of exposure to forearm skin. These results do not support the hypothesis that significant K+ leaching from the stratum corneum into standing sweat is the cause for the previously reported elevated sweat [K+].

Incomplete KLK7 Secretion and Upregulated LEKTI Expression Underlie Hyperkeratotic Stratum Corneum in Atopic Dermatitis.

PubMed

Igawa, Satomi; Kishibe, Mari; Minami-Hori, Masako; Honma, Masaru; Tsujimura, Hisashi; Ishikawa, Junko; Fujimura, Tsutomu; Murakami, Masamoto; Ishida-Yamamoto, Akemi

2017-02-01

Atopic dermatitis (AD) is a common inflammatory skin disorder. Chronic AD lesions present hyperkeratosis, indicating a disturbed desquamation process. KLK7 is a serine protease involved in the proteolysis of extracellular corneodesmosome components, including desmocollin 1 and corneodesmosin, which leads to desquamation. KLK7 is secreted by lamellar granules and upregulated in AD lesional skin. However, despite increased KLK7 protein levels, immunostaining and electron microscopy indicated numerous corneodesmosomes remaining in the uppermost layer of the stratum corneum from AD lesions. We aimed to clarify the discrepancy between KLK7 overexpression and retention of corneodesmosomes on AD corneocytes. Western blot analysis indicated abnormal corneodesmosin degradation patterns in stratum corneum from AD lesions. The KLK activity of tape-stripped corneocytes from AD lesions was not significantly elevated in in situ zymography, which was our new attempt to detect the protease activity more precisely than conventional assays. This ineffective KLK activation was associated with impaired KLK7 secretion from lamellar granules and increased expression of LEKTI in AD. Such imbalances in protease-protease inhibitor interactions could lead to abnormal proteolysis of corneodesmosomes and compact hyperkeratosis. Upregulated expression of LEKTI might be a compensatory mechanism to prevent further barrier dysfunction in AD. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Lecithin-based microemulsions for targeted delivery of ceramide AP into the stratum corneum: formulation, characterizations, and in vitro release and penetration studies.

PubMed

Sahle, Fitsum F; Metz, Hendrik; Wohlrab, Johannes; Neubert, Reinhard H H

2013-02-01

To improve the solubility and penetration of Ceramide AP (CER [AP]) into the stratum corneum that potentially restores the barrier function of aged and affected skin. CER [AP] microemulsions (MEs) were formulated using lecithin, Miglyol® 812 (miglyol) and water-1,2 pentandiol (PeG) mixture as amphiphilic, oily and hydrophilic components, respectively. The nanostructure of the MEs was revealed using electrical conductivity, differential scanning calorimeter (DSC) and electron paramagnetic resonance (EPR) techniques. Photon correlation spectroscopy (PCS) was used to measure the sizes and shape of ME droplets. The release and penetration of the CER into the stratum corneum was investigated in vitro using a multi-layer membrane model. The MEs exhibited excellent thermodynamic stability (>2 years) and loading capacity (0.5% CER [AP]). The pseudo-ternary phase diagrams of the MEs were obtained and PCS results showed that the droplets are spherical in shape and bigger in size. In vitro investigations showed that the MEs exhibited excellent rate and extent of release and penetration. Stable lecithin-based CER [AP] MEs that significantly enhance the solubility and penetration of CER [AP] into the stratum corneum were developed. The MEs also have better properties than the previously reported polyglycerol fatty acid surfactant-based CER [AP] MEs.

Dew point effect of cooled hydrogel pads on human stratum corneum biosurface.

PubMed

Xhauflaire-Uhoda, Emmanuelle; Paquet, Philippe; Piérard, Gérald E

2008-01-01

Cooled hydrogel pads are used to prevent overheating effects of laser therapy. They do not induce cold injuries to the skin, but their more subtle physiological effects have not been thoroughly studied. To describe the changes in transepidermal water loss and electrometric properties of the skin surface following application of cooled hydrogel pads. Measurements were performed on normal forearm skin of 27 healthy volunteers and on freshly excised skin from abdominoplasty. LaserAid hydrogel pads cooled to 4 degrees C were placed for 15 min on the forearm skin. Measurements of transepidermal water loss (TEWL) and electrometric properties (Corneometer, Nova DPM 900) were performed before application and after removal of the cooled pads. A consistent increase in corneometer units, dermal phase meter (DPM) values and TEWL were recorded at removal of the cooled hydrogel pads. Both the in vivo and in vitro assessments brought similar information. The similar changes disclosed in vitro and in vivo suggest that a common physical process is operating in these conditions. The observed phenomenon is opposite to the predicted events given by the Arrhenius law probably because of the combination of cooling and occlusion by the pads. A dew point effect (air temperature at which relative humidity is maximal) is likely involved in the moisture content of the stratum corneum. Thus, the biological impact of using cooling hydrogel pads during laser therapy is different from the effect of a cryogenic spray cooling procedure. The better preservation of the water balance in the stratum corneum by the cooled hydrogel pads could have a beneficial esthetic effect on laser treated areas. (c) 2008 S. Karger AG, Basel.

Deposits from Creams Containing 20% (w/w) Urea and Suppression of Crystallization (Part 2): Novel Analytical Methods of Urea Accumulated in the Stratum Corneum by Tape stripping and Colorimetry.

PubMed

Goto, Norio; Morita, Yutaka; Terada, Katsuhide

2016-01-01

The transfer of urea from a urea formulation to the stratum corneum varies with the formulation base and form, and impacts the formulation's therapeutic effect. Consequently, determining the amount of urea transferred is essential for developing efficient formulations. This study assessed a simple method for measuring the amount of urea accumulated in the stratum corneum. Conventional methods rely on labeling urea used in the formulation with radiocarbon ((14)C) or other radioactive isotopes (RIs), retrieving the transferred urea from the stratum corneum by tape stripping, then quantitating the urea. The handling and use of RIs, however, is subject to legal regulation and can only be performed in sanctioned facilities, so methods employing RIs are neither simple nor convenient. We therefore developed a non-radiolabel method "tape stripping-colorimetry (T-C)" that combines tape stripping with colorimetry (urease-glutamate dehydrogenase (GLDH)) for the quantitative measurement of urea. Urea in the stratum corneum is collected by tape stripping and measured using urease-GLDH, which is commonly used to measure urea nitrogen in blood tests. The results indicate that accurate urea measurement by the T-C method requires the application of 1400 mg (on hairless rats) of a 20% urea solution on a 50 cm(2) (5×10 cm) area. Further, we determined the amount of urea accumulated in the stratum corneum using formulations with different urea concentrations, and the time course of urea accumulation from formulations differing in the rate of urea crystallization. We demonstrate that the T-C method is simple and convenient, with no need for (14)C or other RIs.

Differences in adhesion of Candida albicans 3153A cells exhibiting switch phenotypes to buccal epithelium and stratum corneum.

PubMed

Vargas, K; Wertz, P W; Drake, D; Morrow, B; Soll, D R

1994-04-01

Cells of the laboratory strain 3153A of Candida albicans can be stimulated to undergo high-frequency phenotypic switching by a low dose of UV. We have compared the adhesive properties of cells exhibiting the basic original smooth (o-smooth) phenotype and three switch phenotypes (star, irregular wrinkle, and revertant smooth) to buccal epithelium and stratum corneum. The generalized hierarchy of adhesion is as follows: o-smooth > irregular wrinkle > revertant smooth > star. This is the inverse of the hierarchy of the proportions of elongate hyphae formed by these phenotypes in culture. These results suggest that the differences in adhesion between o-smooth and the three switch phenotypes of strain 3153A reflect, at least in part, the level of interference due to the formation of elongate hyphae, which tend to cause clumping in suspension. No major differences in the levels of adhesion of cells of the different phenotypes between buccal epithelium and stratum corneum were observed. Results which demonstrate that buccal epithelium induces germination (hypha formation) by conditioning the medium are also presented.

Tracking solvents in the skin through atomically resolved measurements of molecular mobility in intact stratum corneum

PubMed Central

Topgaard, Daniel; Sparr, Emma

2017-01-01

Solvents are commonly used in pharmaceutical and cosmetic formulations and sanitary products and cleansers. The uptake of solvent into the skin may change the molecular organization of skin lipids and proteins, which may in turn alter the protective skin barrier function. We herein examine the molecular effects of 10 different solvents on the outermost layer of skin, the stratum corneum (SC), using polarization transfer solid-state NMR on natural abundance 13C in intact SC. With this approach it is possible to characterize the molecular dynamics of solvent molecules when present inside intact SC and to simultaneously monitor the effects caused by the added solvent on SC lipids and protein components. All solvents investigated cause an increased fluidity of SC lipids, with the most prominent effects shown for the apolar hydrocarbon solvents and 2-propanol. However, no solvent other than water shows the ability to fluidize amino acids in the keratin filaments. The solvent molecules themselves show reduced molecular mobility when incorporated in the SC matrix. Changes in the molecular properties of the SC, and in particular alternation in the balance between solid and fluid SC components, may have significant influences on the macroscopic SC barrier properties as well as mechanical properties of the skin. Deepened understanding of molecular effects of foreign compounds in SC fluidity can therefore have strong impact on the development of skin products in pharmaceutical, cosmetic, and sanitary applications. PMID:28028209

The Effect of Gromwell (Lithospermum erythrorhizon) Extract on the Stratum Corneum Hydration and Ceramides Content in Atopic Dermatitis Patients.

PubMed

Cho, Hee Ryung; Cho, Yunhi; Kim, Juyoung; Seo, Dae Bang; Kim, Sung Han; Lee, Sang Jun; Kim, Nack In

2008-06-01

A disruption of the balance between the water content of the stratum corneum (SC) and skin surface lipids may lead to the clinical manifestation of dryness of skin in patients with atopic dermatitis (AD). To determine whether supplementation of gromwell (Lithospermum erythrorhizon), one of herbs used in East Asia in remedies for various abnormal skin conditions, may improve the SC level of hydration and ceramides, major lipid in SC in patients with AD. A total of 28 subjects with AD were randomly assigned into two groups: either gromwell group received dextrose contained capsules with 1.5 g of gromwell extracts or placebo group received only dextrose contained capsules for 10 weeks. In contrast to no alteration of SC hydration and ceramides in placebo group, the SC hydration in gromwell group was significantly increased in parallel with an increase of SC ceramides. Furthermore, % increase of SC hydration in gromwell group bore a positive correlation with the clinical severity, which suggests that the increase of SC hydration in gromwell group was more effective as AD was more severe. Supplementation of gromwell improves SC hydration in parallel with an increase of ceramides in part.

The Effect of Gromwell (Lithospermum erythrorhizon) Extract on the Stratum Corneum Hydration and Ceramides Content in Atopic Dermatitis Patients

PubMed Central

Cho, Hee Ryung; Cho, Yunhi; Kim, Juyoung; Seo, Dae Bang; Kim, Sung Han; Lee, Sang Jun

2008-01-01

Background A disruption of the balance between the water content of the stratum corneum (SC) and skin surface lipids may lead to the clinical manifestation of dryness of skin in patients with atopic dermatitis (AD). Objective To determine whether supplementation of gromwell (Lithospermum erythrorhizon), one of herbs used in East Asia in remedies for various abnormal skin conditions, may improve the SC level of hydration and ceramides, major lipid in SC in patients with AD. Methods A total of 28 subjects with AD were randomly assigned into two groups: either gromwell group received dextrose contained capsules with 1.5 g of gromwell extracts or placebo group received only dextrose contained capsules for 10 weeks. Results In contrast to no alteration of SC hydration and ceramides in placebo group, the SC hydration in gromwell group was significantly increased in parallel with an increase of SC ceramides. Furthermore, % increase of SC hydration in gromwell group bore a positive correlation with the clinical severity, which suggests that the increase of SC hydration in gromwell group was more effective as AD was more severe. Conclusion Supplementation of gromwell improves SC hydration in parallel with an increase of ceramides in part. PMID:27303161

Cutaneous water loss and the development of the stratum corneum of nestling house sparrows (Passer domesticus) from desert and mesic environments.

PubMed

Muñoz-Garcia, Agustí; Williams, Joseph B

2011-01-01

Evaporation through the skin contributes to more than half of the total water loss in birds. Therefore, we expect the regulation of cutaneous water loss (CWL) to be crucial for birds, especially those that live in deserts, to maintain a normal state of hydration. Previous studies in adult birds showed that modifications of the lipid composition of the stratum corneum (SC), the outer layer of the epidermis, were associated with changes in rates of CWL. However, few studies have examined the ontogeny of CWL and the lipids of the SC in nestling birds. In this study, we measured CWL and the lipid composition of the SC during development of nestlings from two populations of house sparrows, one from the deserts of Saudi Arabia and the other from mesic Ohio. We found that desert and mesic nestlings followed different developmental trajectories for CWL. Desert nestlings seemed to make a more frugal use of water than did mesic nestlings. To regulate CWL, nestlings appeared to modify the lipid composition of the SC during ontogeny. Our results also suggest a tighter regulation of CWL in desert nestlings, presumably as a result of the stronger selection pressures to which nestlings are exposed in deserts.

An In vitro Model for Bacterial Growth on Human Stratum Corneum.

PubMed

van der Krieken, Danique A; Ederveen, Thomas H A; van Hijum, Sacha A F T; Jansen, Patrick A M; Melchers, Willem J G; Scheepers, Paul T J; Schalkwijk, Joost; Zeeuwen, Patrick L J M

2016-11-02

The diversity and dynamics of the skin microbiome in health and disease have been studied recently, but adequate model systems to study skin microbiotas in vitro are largely lacking. We developed an in vitro system that mimics human stratum corneum, using human callus as substrate and nutrient source for bacterial growth. The growth of several commensal and pathogenic bacterial strains was measured for up to one week by counting colony-forming units or by quantitative PCR with strain-specific primers. Human skin pathogens were found to survive amidst a minimal microbiome consisting of 2 major skin commensals: Staphylococcus epidermidis and Propionibacterium acnes. In addition, complete microbiomes, taken from the backs of healthy volunteers, were inoculated and maintained using this system. This model may enable the modulation of skin microbiomes in vitro and allow testing of pathogens, biological agents and antibiotics in a medium-throughput format.

Assessing the Relationship between Vitamin D3 and Stratum Corneum Hydration for the Treatment of Xerotic Skin

PubMed Central

Russell, Meghan

2012-01-01

Vitamin D3 has been called the “sunshine” vitamin since the formation of vitamin D is mediated by exposure to sunlight. Vitamin D3 is linked to many health benefits, however serum levels of vitamin D3 have been decreasing over the last few decades and the lower levels of vitamin D3 may have consequences on normal physiology. We investigated the association between serum 25-hydroxyvitamin D (25(OH)D) levels and stratum corneum conductance as well as the effect of topical application of cholecalciferol (vitamin D3) on dry skin. Eighty three subjects were recruited and blood serum levels and skin conductance measurements were taken after a one week washout. A correlation was observed between vitamin D levels and skin moisture content, individuals with lower levels of vitamin D had lower average skin moisture. Subsequently, a 3-week split leg, randomized, vehicle controlled clinical study was conducted on a subset of 61 of the above individuals who were identified with non-sufficient vitamin D serum levels. Topical supplementation with cholecalciferol significantly increased measurements of skin moisturization and resulted in improvements in subjective clinical grading of dry skin. Taken together our finding suggest a relationship between serum vitamin D3 (25(OH)D) levels and hydration of the stratum corneum and further demonstrate the skin moisture benefit from topical application of vitamin D3. PMID:23112909

Assessing the relationship between vitamin D3 and stratum corneum hydration for the treatment of xerotic skin.

PubMed

Russell, Meghan

2012-09-01

Vitamin D(3) has been called the "sunshine" vitamin since the formation of vitamin D is mediated by exposure to sunlight. Vitamin D(3) is linked to many health benefits, however serum levels of vitamin D(3) have been decreasing over the last few decades and the lower levels of vitamin D(3) may have consequences on normal physiology. We investigated the association between serum 25-hydroxyvitamin D (25(OH)D) levels and stratum corneum conductance as well as the effect of topical application of cholecalciferol (vitamin D(3)) on dry skin. Eighty three subjects were recruited and blood serum levels and skin conductance measurements were taken after a one week washout. A correlation was observed between vitamin D levels and skin moisture content, individuals with lower levels of vitamin D had lower average skin moisture. Subsequently, a 3-week split leg, randomized, vehicle controlled clinical study was conducted on a subset of 61 of the above individuals who were identified with non-sufficient vitamin D serum levels. Topical supplementation with cholecalciferol significantly increased measurements of skin moisturization and resulted in improvements in subjective clinical grading of dry skin. Taken together our finding suggest a relationship between serum vitamin D(3) (25(OH)D) levels and hydration of the stratum corneum and further demonstrate the skin moisture benefit from topical application of vitamin D(3).

Effect of detergents on the physicochemical properties of skin stratum corneum: a two-photon excitation fluorescence microscopy study.

PubMed

Bloksgaard, M; Brewer, J R; Pashkovski, E; Ananthapadmanabhan, K P; Sørensen, J A; Bagatolli, L A

2014-02-01

Understanding the structural and dynamical features of skin is critical for advancing innovation in personal care and drug discovery. Synthetic detergent mixtures used in commercially available body wash products are thought to be less aggressive towards the skin barrier when compared to conventional detergents. The aim of this work is to comparatively characterize the effect of a mild synthetic cleanser mixture (SCM) and sodium dodecyl sulphate (SDS) on the hydration state of the intercellular lipid matrix and on proton activity of excised skin stratum corneum (SC). Experiments were performed using two-photon excitation fluorescence microscopy. Fluorescent images of fluorescence reporters sensitive to proton activity and hydration of SC were obtained in excised skin and examined in the presence and absence of SCM and SDS detergents. Hydration of the intercellular lipid matrix to a depth of 10 μm into the SC was increased upon treatment with SCM, whereas SDS shows this effect only at the very surface of SC. The proton activity of SC remained unaffected by treatment with either detergent. While our study indicates that the SC is very resistant to external stimuli, it also shows that, in contrast to the response to SDS, SCM to some extent modulates the in-depth hydration properties of the intercellular lipid matrix within excised skin SC. © 2013 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Role of lipids in the formation and maintenance of the cutaneous permeability barrier.

PubMed

Feingold, Kenneth R; Elias, Peter M

2014-03-01

The major function of the skin is to form a barrier between the internal milieu and the hostile external environment. A permeability barrier that prevents the loss of water and electrolytes is essential for life on land. The permeability barrier is mediated primarily by lipid enriched lamellar membranes that are localized to the extracellular spaces of the stratum corneum. These lipid enriched membranes have a unique structure and contain approximately 50% ceramides, 25% cholesterol, and 15% free fatty acids with very little phospholipid. Lamellar bodies, which are formed during the differentiation of keratinocytes, play a key role in delivering the lipids from the stratum granulosum cells into the extracellular spaces of the stratum corneum. Lamellar bodies contain predominantly glucosylceramides, phospholipids, and cholesterol and following the exocytosis of lamellar lipids into the extracellular space of the stratum corneum these precursor lipids are converted by beta glucocerebrosidase and phospholipases into the ceramides and fatty acids, which comprise the lamellar membranes. The lipids required for lamellar body formation are derived from de novo synthesis by keratinocytes and from extra-cutaneous sources. The lipid synthetic pathways and the regulation of these pathways are described in this review. In addition, the pathways for the uptake of extra-cutaneous lipids into keratinocytes are discussed. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias. Published by Elsevier B.V.

Effects of atmospheric relative humidity on Stratum Corneum structure at the molecular level: ex vivo Raman spectroscopy analysis.

PubMed

Vyumvuhore, Raoul; Tfayli, Ali; Duplan, Hélène; Delalleau, Alexandre; Manfait, Michel; Baillet-Guffroy, Arlette

2013-07-21

Skin hydration plays an important role in the optimal physical properties and physiological functions of the skin. Despite the advancements in the last decade, dry skin remains the most common characteristic of human skin disorders. Thus, it is important to understand the effect of hydration on Stratum Corneum (SC) components. In this respect, our interest consists in correlating the variations of unbound and bound water content in the SC with structural and organizational changes in lipids and proteins using a non-invasive technique: Raman spectroscopy. Raman spectra were acquired on human SC at different relative humidity (RH) levels (4-75%). The content of different types of water, bound and free, was measured using the second derivative and curve fitting of the Raman bands in the range of 3100-3700 cm(-1). Changes in lipidic order were evaluated using νC-C and νC-H. To analyze the effect of RH on the protein structure, we examined in the Amide I region, the Fermi doublet of tyrosine, and the νasymCH3 vibration. The contributions of totally bound water were found not to vary with humidity, while partially bound water varied with three different rates. Unbound water increased greatly when all sites for bound water were saturated. Lipid organization as well as protein deployment was found to be optimal at intermediate RH values (around 60%), which correspond to the maximum of SC water binding capacity. This analysis highlights the relationship between bound water, the SC barrier state and the protein structure and elucidates the optimal conditions. Moreover, our results showed that increased content of unbound water in the SC induces disorder in the structures of lipids and proteins.

[Effects of Frankincense and Myrrh essential oil on transdermal absorption of ferulic acid in Chuanxiong].

PubMed

Guan, Yong-Mei; Tao, Ling; Zhu, Xiao-Fang; Zang, Zhen-Zhong; Jin, Chen; Chen, Li-Hua

2017-09-01

The aim of this paper was to explore the effects of Frankincense and Myrrh essential oil on transdermal absorption, and investigate the mechanism of permeation on the microstructure and molecular structure of stratum corneum. Through the determination of stratum corneum/medium partition coefficient of ferulicacid in Chuanxiong influenced by Frankincense and Myrrh essential oil, the effects of volatile oil of frankincense and Myrrh on the the microscopic and molecular structure of stratum corneum were explored by observation of skin stratum corneum structure under scanning electron microscopy, and investigation of frankincense and myrrh essential oil effects on the molecular structure of keratin and lipids in stratum corneum under Fourier transform infrared spectroscopy. The results showed that the oil could enhance the distribution of ferulic acid in the stratum corneum and medium, and to a certain extent damaged the imbricate structure of stratum corneum which was originally regularly, neatly, and closely arranged; some epidermal scales turned upward, with local peeling phenomenon. In addition, frankincense and myrrh essential oil caused the relative displacement of CH2 stretching vibration peak of stratum corneum lipids and amide stretching vibration peak of stratum corneum keratin, indicating that frankincense and myrrh essential oil may change the conformation of lipid and keratin in the stratum corneum, increase the bilayer liquidity of the stratum corneum lipid, and change the orderly and compact structure to increase the skin permeability and reduce the effect of barrier function. It can be concluded that Frankincense and Myrrh essential oil can promote the permeation effect by increasing the distribution of drugs in the stratum corneum and changing the structure of the stratum corneum. Copyright© by the Chinese Pharmaceutical Association.

Effect of topically applied dexpanthenol on epidermal barrier function and stratum corneum hydration. Results of a human in vivo study.

PubMed

Gehring, W; Gloor, M

2000-07-01

In a randomized, double-blind, placebo-controlled study the effect of topical dexpanthenol (CAS 81-13-0) formulated in two different lipophilic vehicles on epidermal barrier function in vivo was carried out. Seven days' treatment with dexpanthenol improved stratum corneum hydration and reduced transepidermal water loss. Active treatment was statistically different from the vehicle control on both measures. Our results suggest that topical dexpanthenol formulated in either lipophilic vehicle stabilizes the skin barrier function.

Controlled penetration of ceramides into and across the stratum corneum using various types of microemulsions and formulation associated toxicity studies.

PubMed

Sahle, Fitsum F; Wohlrab, Johannes; Neubert, Reinhard H H

2014-02-01

Several skin diseases such as psoriasis and atopic dermatitis are associated with the depletion or disturbance of stratum corneum (SC) lipids such as ceramides (CERs), free fatty acids and cholesterol. Studies suggested that replenishment of these lipids might help to treat diseased, affected or aged skin. With this premises in mind, there are some formulations in the market that contain SC lipids and currently, to facilitate permeation of the lipids deep into the SC, various CERs, and other SC lipid microemulsions (MEs) were developed and characterised using lecithin or TEGO® CARE PL 4 (TCPL4) as base surfactants. However, to date, there are no reports that involve the permeability of SC lipids into and across the SC, and therefore, the penetration of CER [NP] as a model ceramide from various formulations was investigated ex vivo using Franz diffusion cell. Besides, the toxicity of the MEs was assessed using hen's egg test chorioallantoic membrane (HET-CAM). The results of the study showed that CER [NP] could not permeate into deeper layers of the SC from a conventional hydrophilic cream. Unlike the cream, CER [NP] permeated into the deeper layers of the SC from both type of MEs, where permeation of the CER was more and into deeper layers from droplet type and lecithin-based MEs than bicontinuous (BC) type and TCPL4 based MEs, respectively. The CER also permeated into deeper layers from ME gels which was, however, shallow and to a lesser extent when compared with the MEs. The results of HET-CAM showed that both MEs are safe to be used topically, with lecithin-based MEs exhibiting better safety profiles than TCPL4 based MEs. Concluding, the study showed that the MEs are safe to be used on the skin for the controlled penetration of CER [NP] deep into the SC. Copyright © 2013 Elsevier B.V. All rights reserved.

Drug Delivery Through the Skin: Molecular Simulations of Barrier Lipids to Design more Effective Noninvasive Dermal and Transdermal Delivery Systems for Small Molecules Biologics and Cosmetics

DOE Office of Scientific and Technical Information (OSTI.GOV)

J Torin Huzil; S Sivaloganathan; M Kohandel

The delivery of drugs through the skin provides a convenient route of administration that is often preferable to injection because it is noninvasive and can typically be self-administered. These two factors alone result in a significant reduction of medical complications and improvement in patient compliance. Unfortunately, a significant obstacle to dermal and transdermal drug delivery alike is the resilient barrier that the epidermal layers of the skin, primarily the stratum corneum, presents for the diffusion of exogenous chemical agents. Further advancement of transdermal drug delivery requires the development of novel delivery systems that are suitable for modern, macromolecular protein andmore » nucleotide therapeutic agents. Significant effort has already been devoted to obtain a functional understanding of the physical barrier properties imparted by the epidermis, specifically the membrane structures of the stratum corneum. However, structural observations of membrane systems are often hindered by low resolutions, making it difficult to resolve the molecular mechanisms related to interactions between lipids found within the stratum corneum. Several models describing the molecular diffusion of drug molecules through the stratum corneum have now been postulated, where chemical permeation enhancers are thought to disrupt the underlying lipid structure, resulting in enhanced permeability. Recent investigations using biphasic vesicles also suggested a possibility for novel mechanisms involving the formation of complex polymorphic lipid phases. In this review, we discuss the advantages and limitations of permeation-enhancing strategies and how computational simulations, at the atomic scale, coupled with physical observations can provide insight into the mechanisms of diffusion through the stratum corneum.« less

How Sensitive Are Transdermal Transport Predictions by Microscopic Stratum Corneum Models to Geometric and Transport Parameter Input?

PubMed

Wen, Jessica; Koo, Soh Myoung; Lape, Nancy

2018-02-01

While predictive models of transdermal transport have the potential to reduce human and animal testing, microscopic stratum corneum (SC) model output is highly dependent on idealized SC geometry, transport pathway (transcellular vs. intercellular), and penetrant transport parameters (e.g., compound diffusivity in lipids). Most microscopic models are limited to a simple rectangular brick-and-mortar SC geometry and do not account for variability across delivery sites, hydration levels, and populations. In addition, these models rely on transport parameters obtained from pure theory, parameter fitting to match in vivo experiments, and time-intensive diffusion experiments for each compound. In this work, we develop a microscopic finite element model that allows us to probe model sensitivity to variations in geometry, transport pathway, and hydration level. Given the dearth of experimentally-validated transport data and the wide range in theoretically-predicted transport parameters, we examine the model's response to a variety of transport parameters reported in the literature. Results show that model predictions are strongly dependent on all aforementioned variations, resulting in order-of-magnitude differences in lag times and permeabilities for distinct structure, hydration, and parameter combinations. This work demonstrates that universally predictive models cannot fully succeed without employing experimentally verified transport parameters and individualized SC structures. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Quantification of free fatty acids in human stratum corneum using tandem mass spectrometry and surrogate analyte approach.

PubMed

Dapic, Irena; Kobetic, Renata; Brkljacic, Lidija; Kezic, Sanja; Jakasa, Ivone

2018-02-01

The free fatty acids (FFAs) are one of the major components of the lipids in the stratum corneum (SC), the uppermost layer of the skin. Relative composition of FFAs has been proposed as a biomarker of the skin barrier status in patients with atopic dermatitis (AD). Here, we developed an LC-ESI-MS/MS method for simultaneous quantification of a range of FFAs with long and very long chain length in the SC collected by adhesive tape (D-Squame). The method, based on derivatization with 2-bromo-1-methylpyridinium iodide and 3-carbinol-1-methylpyridinium iodide, allowed highly sensitive detection and quantification of FFAs using multiple reaction monitoring. For the quantification, we applied a surrogate analyte approach and internal standardization using isotope labeled derivatives of FFAs. Adhesive tapes showed the presence of several FFAs, which are also present in the SC, a problem encountered in previous studies. Therefore, the levels of FFAs in the SC were corrected using C12:0, which was present on the adhesive tape, but not detected in the SC. The method was applied to SC samples from patients with atopic dermatitis and healthy subjects. Quantification using multiple reaction monitoring allowed sufficient sensitivity to analyze FFAs of chain lengths C16-C28 in the SC collected on only one tape strip. Copyright © 2017 John Wiley & Sons, Ltd.

Impact of the ceramide subspecies on the nanostructure of stratum corneum lipids using neutron scattering and molecular dynamics simulations. Part I: impact of CER[NS].

PubMed

Schmitt, Thomas; Gupta, Rakesh; Lange, Stefan; Sonnenberger, Stefan; Dobner, Bodo; Hauß, Thomas; Rai, Beena; Neubert, Reinhard H H

2018-05-30

For this study mixtures based on the ceramides [NS] (NS = non-hydroxy-sphingosine) and [AP] (AP = α-hydroxy-phytosphingosine) in a 2:1 and 1:2 ratio, together with cholesterol and lignoceric acid, were investigated. These mixtures are modelling the uppermost skin layer, the stratum corneum. Neutron diffraction, utilizing specifically deuterated ceramide molecules, was used to obtain a maximum amount of experimental detail. Highly detailed molecular dynamics simulations were used to generate even more information from the experimental data. It was possible to observe a single lamellar phase for both systems. They had a lamellar repeat distance of 5.43 ± 0.05 nm for the [NS]/[AP] 2:1 and a slightly shorter one of 5.34 ± 0.05 nm for the 1:2 system. The structure and water content was uninfluenced by excess humidity. Both the experimental and simulation data indicated slightly tilted ceramides, with their C24 chains overlapping in the lamellar mid-plane. This arrangement is well comparable to systems investigated before. The structure of both systems, except for the differing repeat distance, looks similar at first. However, on a smaller scale there were various distinct differences, demonstrating only low redundancy between the different ceramide species, despite only minor chemical differences. The mainly ceramide [AP] determined 1:2 system has a slightly smaller repeat distance. This is a result of a tighter arrangement of the lipids chain along the bilayer normal and increased overlapping of the long chains in the lamellar middle. For the CER[NS] some novel features could be shown, despite it being the overall most investigated ceramide. These include the low adaptability to changed lateral interactions, leading to an increased chain opening. This effect could explain its low miscibility with other lipids. The investigated model systems allows it to directly compare results from the literature which have used ceramide [NS] to the most recent

Effects of silicone gel sheet on the stratum corneum hydration.

PubMed

Suetak, T; Sasai, S; Zhen, Y X; Tagami, H

2000-09-01

Various groups have reported the efficacy of treatment with topical silicone gel sheet (SGS) for keloids and hypertrophic scars. Because its hydrating effect on the stratum corneum (SC) has been suggested as a mechanism underlying its therapeutic effectiveness, we evaluated it by comparing it with simple plastic film occlusion. With biophysical instruments we assessed the water content of the skin surface as well as its water evaporation on the flexor aspects of bilateral forearms of 10 healthy volunteers for 30min after removal of dressings of SGS or a plastic film that were applied either for 1 day or for 7 days. Occlusion with SGS or plastic film induced hydration of the skin surface, which was followed by an initial quick and later slow process of dehydration when the skin was exposed to the ambient atmosphere. The magnitude of the increase in hydration induced by SGS was always smaller than that of the plastic film occlusion and, unlike the latter treatment, hydration became less with repetition of SGS treatment. On day 7, the SC hydration quickly reduced to the level of non-treated control skin after removal of the dressings. An in vivo test demonstrated that the water-holding capacity of the SC normalised after 7 days of SGS treatment. SGS probably produces a favourable condition for the skin by protecting it from various environmental stimuli, while keeping the SC in an adequately but not over-hydrated condition.

In vivo confocal Raman spectroscopic analysis of the effects of IR radiation in the stratum corneum of human skin (Conference Presentation)

NASA Astrophysics Data System (ADS)

Rajasekaran, Ramu; Bergamo Lopes, Monica; Magrini, Taciana D.; Figueira Lopes Cançado, Ana Clara; Abrahao Martin, Airton

2017-02-01

Stratum Corneum is the outer covering of the body, which serves as a barrier to infection. The composition of the skin changes withexternal environmental factors, such as temperature, sun irradiation, air pollutants, chemical hazards, as well as other factors.Solar radiation,especially IR radiation is being used as medicine for wound healing processes, in cosmetology, in physiotherapy and warming of muscles. Also, it was reported that the IR radiation produces free radicals and the excess production of free radicals causes irreversible damages. It has been reported that heat may be transmitted by IR radiation, which results in raised skin temperature and the chronic heat exposure of human skin may cause alterations. Erythema igne is one such disease known to be caused by chronic heat exposure. Many techniques have been adopted for monitoring the changes in the skin, which includes the tape stripping and biopsy as the primary methodology. However, these in vitro techniques are invasive, time consuming, and may not provide the actual information as in in vivo conditions. Confocal Raman spectroscopy,which is non-invasive and real time was considered as a potential tool for the in vivo analysis of the distribution and characteristics of different metabolic conditions and their variations of the skin. In this regard, we aimed at in vivo characterization of the IR induced changes in the stratum corneum of human volunteers. The results of Raman spectral signatures with respect to the control and IR exposed skin will be discussed.

Stratum corneum cytokines and skin irritation response to sodium lauryl sulfate.

PubMed

De Jongh, Cindy M; Verberk, Maarten M; Withagen, Carien E T; Jacobs, John J L; Rustemeyer, Thomas; Kezic, Sanja

2006-06-01

Little is known about cytokines involved in chronic irritant contact dermatitis. Individual cytokine profiles might explain at least part of the differences in the individual response to irritation. Our objective was to investigate the relation between baseline stratum corneum (SC) cytokine levels and the skin response to a single and a repeated irritation test. This study also aimed to determine changes in SC cytokine levels after repeated irritation. Transepidermal water loss (TEWL) and erythema were measured in 20 volunteers after single 24-hr exposure to 1% sodium lauryl sulfate (SLS), and during and after repeated exposure to 0.1% SLS over a 3-week period. SC cytokine levels were measured from an unexposed skin site and from the repeatedly exposed site. Interleukin (IL)-1alpha decreased by 30% after repeated exposure, while IL-1RA increased 10-fold and IL-8 increased fourfold. Baseline IL-1RA and IL-8 values were predictors of TEWL and erythema after single exposure (r = 0.55-0.61). 6 subjects showed barrier recovery during repeated exposure. Baseline IL-1RA and IL-8 levels are likely to be indicators of higher skin irritability after single exposure to SLS. Barrier repair in some of the subjects might explain the lack of agreement between the TEWL response after single and repeated irritation.

Amputee skin condition: occlusion, stratum corneum hydration and free amino acid levels.

PubMed

Visscher, Marty O; Robinson, Marisa; Fugit, Benetta; Rosenberg, Richard J; Hoath, Steven B; Randall Wickett, R

2011-03-01

Patients with a prosthetic limb report negative skin effects, including irritation, rash and chafing, which can lead to infection, discomfort and reduced wear time to significantly impact normal activities. The aims were to examine the epidermal integrity (transepidermal water loss, TEWL), stratum corneum (SC) hydration [moisture accumulation rate (MAT)], friction and biomechanical properties in active below the knee amputees and to determine the effects of an inert sock liner on skin condition. The liner reduced hydration, TEWL and friction and increased elasticity versus the amputee's conventional skin care methods. Residual limb TEWL was increased and MAT was reduced versus the contralateral normal skin. In a second study, we hypothesized that complete occlusion would decrease free amino acids (FAA) and quantified them by high performance liquid chromatography in an adult volar forearm model. Occlusion with a water vapor impermeable wet dressing led to increased TEWL, erythema and dryness and reduced MAT versus normal skin, comparable to the results in the amputees. The FAA levels were significantly reduced for the occluded sites. The results suggest that residual limb occlusion in amputees may block the formation of FAA in the upper SC. Therapies based on replacement of water binding FAAs, may alleviate the consequences of long-term occlusion.

Retarder action of isosorbide in a microemulsion for a targeted delivery of ceramide NP into the stratum corneum.

PubMed

Steinbach, S C; Triani, R; Bennedsen, L; Gabel, A; Haeusler, O; Wohlrab, J; Neubert, R H H

2017-08-01

Ceramide [NP] is an integral component of the stratum corneum (SC) lipid matrix and is capable of forming tough and stable lamellar structures. It was proven, that in skin diseases as psoriasis or atopic dermatitis different ceramide (CER) classes, including [NP], are degraded. It is obvious that topically application of CER on impaired skin is useful for repairing the skin barrier but a tendency for low penetration due to its poor solubility in conventional dosage forms was observed. Therefore, a stable and physiologic compatible colloidal carrier system, a microemulsion (ME), was developed and characterized. The increasing knowledge of the new colloidal systems in this last decade shows their benefits in dermal application. Isosorbide (Polysorb P) was incorporated into the ME developed. It was expected that Polysorb P has a retarder potential in order to accumulate the CER in the SC, the outermost layer of the skin. Thereby the CER [NP] would be able to interact with the affected skin layers to strengthen the skin barrier. The release and penetration behavior of the CER [NP] from the ME was assessed ex vivo in a Franz diffusion cell. The results of the study showed that CER [NP] penetrate largely in the upper layers of the skin (from SC to stratum basale), which was the desired region. A recovery in the acceptor could not be detected that underlines an accumulation in upper layers. Furthermore, significantly increased values for the SC for the ME with retarder were not received. No differences in the concentrations of CER [NP] were observed. However, the toxicity of MEs was investigated using heńs egg test chorioallantoic membrane (HET-CAM). For the isosorbide-containing ME no difference was obtained in comparison to the non-containing. The results showed that both MEs are safe to be used on the skin for the controlled penetration of CER [NP] into the skin. The isosorbide had no effect on the irritating effect as well as on the penetration of the used CER.

The Structure of the Human Vaginal Stratum Corneum and its Role in Immune Defense

PubMed Central

Anderson, Deborah J.; Marathe, Jai; Pudney, Jeffrey

2014-01-01

The superficial layers of the human vaginal epithelium, which form an interface between host and environment, are comprised of dead flattened cells that have undergone a terminal cell differentiation program called cornification. This entails extrusion of nuclei and intercellular organelles, and the depletion of functional DNA and RNA precluding the synthesis of new proteins. As a consequence, the terminally differentiated cells do not maintain robust intercellular junctions and have a diminished capacity to actively respond to microbial exposure, yet the vaginal stratum corneum (SC) mounts an effective defense against invasive microbial infections. The vaginal SC in reproductive aged women is comprised of loosely connected glycogen-filled cells which are permeable to bacterial and viral microbes as well as molecular and cellular mediators of immune defense. We propose here that the vaginal SC provides a unique microenvironment that maintains vaginal health by fostering endogenous lactobacillii and retaining critical mediators of acquired and innate immunity. A better understanding of the molecular and physicochemical properties of the vaginal SC could promote the design of more effective topical drugs and microbicides. PMID:24661416

Dodecyl Amino Glucoside Enhances Transdermal and Topical Drug Delivery via Reversible Interaction with Skin Barrier Lipids.

PubMed

Kopečná, Monika; Macháček, Miloslav; Prchalová, Eva; Štěpánek, Petr; Drašar, Pavel; Kotora, Martin; Vávrová, Kateřina

2017-03-01

Skin permeation/penetration enhancers are substances that enable drug delivery through or into the skin. To search for new enhancers with high but reversible activity and acceptable toxicity, we synthesized a series of D-glucose derivatives, both hydrophilic and amphiphilic. Initial evaluation of the ability of these sugar derivatives to increase permeation and penetration of theophylline through/into human skin compared with a control (no enhancer) or sorbitan monolaurate (Span 20; positive control) revealed dodecyl 6-amino-6-deoxy-α-D-glucopyranoside 5 as a promising enhancer. Furthermore, this amino sugar 5 increased epidermal concentration of a highly hydrophilic antiviral cidofovir by a factor of 7. The effect of compound 5 on skin electrical impedance suggested its direct interaction with the skin barrier. Infrared spectroscopy of isolated stratum corneum revealed no effect of enhancer 5 on the stratum corneum proteins but an overall decrease in the lipid chain order. The enhancer showed acceptable toxicity on HaCaT keratinocyte and 3T3 fibroblast cell lines. Finally, transepidermal water loss returned to baseline values after enhancer 5 had been removed from the skin. Compound 5, a dodecyl amino glucoside, is a promising enhancer that acts through a reversible interaction with the stratum corneum lipids.

Determination of the influence of C24 D/(2R)- and L/(2S)-isomers of the CER[AP] on the lamellar structure of stratum corneum model systems using neutron diffraction.

PubMed

Schmitt, Thomas; Lange, Stefan; Sonnenberger, Stefan; Dobner, Bodo; Demé, Bruno; Neubert, Reinhard H H; Gooris, Gert; Bouwstra, Joke A

2017-12-01

This study was able to investigate the different influence of the d- and l-ceramide [AP] on the lamellar as well as molecular nanostructure of stratum corneum simulating lipid model mixtures. In this case, neutron diffraction together with specifically deuterated ceramide was used as an effective tool to investigate the lamellar and the molecular nanostructure of the mixtures. It could clearly be demonstrated, that both isomers show distinctly different characteristics, even though the variation between both is only a single differently arranged OH-group. The l-ceramide [AP] promotes a crystalline like phase behaviour even if mixed with ceramide [NP], cholesterol and free fatty acids. The d-ceramide [AP] only shows crystalline-like features if mixed only with cholesterol and free fatty acids but adopts a native-like behaviour if additionally mixed with ceramide [NP]. It furthermore demonstrates that the l-ceramide [AP] should not be used for any applications concerning ceramide substitution. It could however possibly serve its own purpose, if this crystalline like behaviour has some kind of positive influence on the SC or can be utilized for any practical applications. The results obtained in this study demonstrate that the diastereomers of ceramide [AP] are an attractive target for further research because their influence on the lamellar as well as the nanostructure is exceptionally strong. Additionally, the results furthermore show a very strong influence on hydration of the model membrane. With these properties, the d-ceramide [AP] could be effectively used to simulate native like behaviour even in very simple mixtures and could also have a strong impact on the native stratum corneum as well as high relevance for dermal ceramide substitution. The unnatural l-ceramide [AP] on the other hand should be investigated further, to assess its applicability. Copyright © 2017 Elsevier B.V. All rights reserved.

Subclass distribution of IgG antibodies to the rat oesophagus stratum corneum (so-called anti-keratin antibodies) in rheumatoid arthritis.

PubMed Central

Vincent, C; Serre, G; Basile, J P; Lestra, H C; Girbal, E; Sebbag, M; Soleilhavoup, J P

1990-01-01

Serum IgG, labelling the stratum corneum of the rat oesophagus epithelium, so-called anti-keratin antibodies (AKA) constitute the most specific marker for the diagnosis of rheumatoid arthritis. In this study, we investigated 31 IgG AKA-positive rheumatoid sera and 21 control sera from patients with non-rheumatoid inflammatory rheumatic diseases. The serum level of IgG1,2,3 and 4 was determined by radial immunodiffusion and the subclass distribution of IgG AKA by a three-step semi-quantitative immunofluorescence assay using standard monoclonal antibodies specific for each of the four human IgG subclasses. In the rheumatoid sera, the serum level of IgG1 was found to be significantly increased and the level of IgG2 significantly decreased with regard to the control sera, while the levels of IgG3 and 4 as well as total IgG were in the normal range. IgG1,2,3, and 4 AKA were detected in 27 (87%), 6 (19%), 4 (13%) and 11 (35%) of the 31 rheumatoid sera, respectively, and were found to be independent of the clinical and biological indices of the disease. In spite of inter-individual heterogeneity, two predominant profiles were distinguished: IgG1 (alone) and IgG(1 + 4), which together represented 18 sera (58%). The large predominance of IgG1 AKA and the quasi-absence of IgG2 AKA suggest that the recognized antigen may be partly comprised of protein. Moreover, the high frequency of occurrence of IgG4 AKA might result from chronic exposure to the eliciting antigen, which could be a genuine autoantigen since we demonstrated that it is also present in the stratum corneum of human epidermis. Images Fig. 1 PMID:1696185

In vivo confocal Raman microscopic determination of depth profiles of the stratum corneum lipid organization influenced by application of various oils.

PubMed

Choe, ChunSik; Schleusener, Johannes; Lademann, Jürgen; Darvin, Maxim E

2017-08-01

The intercellular lipids (ICL) of stratum corneum (SC) play an important role in maintaining the skin barrier function. The lateral and lamellar packing order of ICL in SC is not homogenous, but rather depth-dependent. This study aimed to analyze the influence of the topically applied mineral-derived (paraffin and petrolatum) and plant-derived (almond oil and jojoba oil) oils on the depth-dependent ICL profile ordering of the SC in vivo. Confocal Raman microscopy (CRM), a unique tool to analyze the depth profile of the ICL structure non-invasively, is employed to investigate the interaction between oils and human SC in vivo. The results show that the response of SC to oils' permeation varies in the depths. All oils remain in the upper layers of the SC (0-20% of SC thickness) and show predominated differences of ICL ordering from intact skin. In these depths, skin treated with plant-derived oils shows more disordered lateral and lamellar packing order of ICL than intact skin (p<0.05). In the intermediate layers of SC (30-50% of SC thickness), the oils do not influence the lateral packing order of SC ICL (p>0.1), except plant-derived oils at the depth 30% of SC thickness. In the deeper layers of the SC (60-100% of SC thickness), no difference between ICL lateral packing order of the oil-treated and intact skin can be observed, except that at the depths of 70-90% of the SC thickness, where slight changes with more disorder states are measured for plant-derived oil treated skin (p<0.1), which could be explained by the penetration of free fatty acid fractions in the deep-located SC areas. Both oil types remain in the superficial layers of the SC (0-20% of the SC thickness). Skin treated with mineral- and plant-derived oils shows significantly higher disordered lateral and lamellar packing order of ICL in these layers of the SC compared to intact skin. Plant-derived oils significantly changed the ICL ordering in the depths of 30% and 70-90% of the SC thickness, which is

Stratum corneum lipid liposome-encapsulated panomycocin: preparation, characterization, and the determination of antimycotic efficacy against Candida spp. isolated from patients with vulvovaginitis in an in vitro human vaginal epithelium tissue model.

PubMed

İzgü, Fatih; Bayram, Günce; Tosun, Kübra; İzgü, Demet

2017-01-01

In this study, a liposomal lyophilized powder formulation of panomycocin was developed for therapeutic purposes against vulvovaginal candidiasis which affects 80% of women worldwide. Panomycocin is a potent antimycotic protein secreted by the yeast Wickerhamomyces anomalus NCYC 434. This study involved the preparation of panomycocin-loaded stratum corneum lipid liposomes (SCLLs), characterization of the SCLLs, and determination of antimycotic efficacy of the formulation against Candida albicans and Candida glabrata clinical vaginal isolates in a human vaginal epithelium tissue model. The encapsulation and loading efficiencies of SCLLs were 73% and 76.8%, respectively. In transmission electron microscopy images, the SCLLs appeared in the submicron size range. Dynamic light scattering analyses showed that the SCLLs had uniform size distribution. Zeta potential measurements revealed stable and positively charged SCLLs. In Fourier transform infrared spectroscopy analyses, no irreversible interactions between the encapsulated panomycocin and the SCLLs were detected. The SCLLs retained >98% of encapsulated panomycocin in aqueous solution up to 12 hours. The formulation was fungicidal at the same minimum fungicidal concentration values for non-formulated pure panomycocin when tested on an in vitro model of vaginal candidiasis. This is the first study in which SCLLs and a protein as an active ingredient have been utilized together in a formulation. The results obtained in this study led us to conduct further preclinical trials of this formulation for the development of an effective topical anti-candidal drug with improved safety.

Stratum corneum lipid liposome-encapsulated panomycocin: preparation, characterization, and the determination of antimycotic efficacy against Candida spp. isolated from patients with vulvovaginitis in an in vitro human vaginal epithelium tissue model

PubMed Central

İzgü, Fatih; Bayram, Günce; Tosun, Kübra; İzgü, Demet

2017-01-01

In this study, a liposomal lyophilized powder formulation of panomycocin was developed for therapeutic purposes against vulvovaginal candidiasis which affects 80% of women worldwide. Panomycocin is a potent antimycotic protein secreted by the yeast Wickerhamomyces anomalus NCYC 434. This study involved the preparation of panomycocin-loaded stratum corneum lipid liposomes (SCLLs), characterization of the SCLLs, and determination of antimycotic efficacy of the formulation against Candida albicans and Candida glabrata clinical vaginal isolates in a human vaginal epithelium tissue model. The encapsulation and loading efficiencies of SCLLs were 73% and 76.8%, respectively. In transmission electron microscopy images, the SCLLs appeared in the submicron size range. Dynamic light scattering analyses showed that the SCLLs had uniform size distribution. Zeta potential measurements revealed stable and positively charged SCLLs. In Fourier transform infrared spectroscopy analyses, no irreversible interactions between the encapsulated panomycocin and the SCLLs were detected. The SCLLs retained >98% of encapsulated panomycocin in aqueous solution up to 12 hours. The formulation was fungicidal at the same minimum fungicidal concentration values for non-formulated pure panomycocin when tested on an in vitro model of vaginal candidiasis. This is the first study in which SCLLs and a protein as an active ingredient have been utilized together in a formulation. The results obtained in this study led us to conduct further preclinical trials of this formulation for the development of an effective topical anti-candidal drug with improved safety. PMID:28831255

Keratin-lipid structural organization in the corneous layer of snake.

PubMed

Ripamonti, Alberto; Alibardi, Lorenzo; Falini, Giuseppe; Fermani, Simona; Gazzano, Massimo

2009-12-01

The shed epidermis (molt) of snakes comprises four distinct layers. The upper two layers, here considered as beta-layer, contain essentially beta-keratin. The following layer, known as mesos-layer, is similar to the human stratum corneum, and is formed by thin cells surrounded by intercellular lipids. The latter layer mainly contains alpha-keratin. In this study, the molecular assemblies of proteins and lipids contained in these layers have been analyzed in the scale of two species of snakes, the elapid Tiger snake (TS, Notechis scutatus) and the viperid Gabon viper (GV, Bitis gabonica). Scanning X-ray micro-diffraction, FTIR and Raman spectroscopies, thermal analysis, and scanning electron microscopy experiments confirm the presence of the three layers in the GV skin scale. Conversely, in the TS molt a typical alpha-keratin layer appears to be absent. In the latter, experimental data suggest the presence of two domains similar to those found in the lipid intercellular matrix of stratum corneum. X-ray diffraction data also allow to determine the relative orientation of keratins and lipids. The keratin fibrils are randomly oriented inside the layers parallel to the surface of scales while the lipids are organized in lamellar structures having aliphatic chains normal to the scale surface. The high ordered lipid organization in the mature mesos layer probably increases its effectiveness in limiting water-loss.

Thermal phase transition behavior of lipid layers on a single human corneocyte cell.

PubMed

Imai, Tomohiro; Nakazawa, Hiromitsu; Kato, Satoru

2013-09-01

We have improved the selected area electron diffraction method to analyze the dynamic structural change in a single corneocyte cell non-invasively stripped off from human skin surface. The improved method made it possible to obtain reliable diffraction images to trace the structural change in the intercellular lipid layers on a single corneocyte cell during heating from 24°C to 100°C. Comparison of the results with those of synchrotron X-ray diffraction experiments on human stratum corneum sheets revealed that the intercellular lipid layers on a corneocyte cell exhibit essentially the same thermal phase transitions as those in a stratum corneum sheet. These results suggest that the structural features of the lipid layers are well preserved after the mechanical stripping of the corneocyte cell. Moreover, electron diffraction analyses of the thermal phase transition behaviors of the corneocyte cells that had the lipid layers with different distributions of orthorhombic and hexagonal domains at 24°C suggested that small orthorhombic domains interconnected with surrounding hexagonal domains transforms in a continuous manner into new hexagonal domains. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Fatty acids are required for epidermal permeability barrier function.

PubMed

Mao-Qiang, M; Elias, P M; Feingold, K R

1993-08-01

The permeability barrier is mediated by a mixture of ceramides, sterols, and free fatty acids arranged as extracellular lamellar bilayers in the stratum corneum. Whereas prior studies have shown that cholesterol and ceramides are required for normal barrier function, definitive evidence for the importance of nonessential fatty acids is not available. To determine whether epidermal fatty acid synthesis also is required for barrier homeostasis, we applied 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA), an inhibitor of acetyl CoA carboxylase, after disruption of the barrier by acetone or tape stripping. TOFA inhibits epidermal fatty acid by approximately 50% and significantly delays barrier recovery. Moreover, coadministration of palmitate with TOFA normalizes barrier recovery, indicating that the delay is due to a deficiency in bulk fatty acids. Furthermore, TOFA treatment also delays the return of lipids to the stratum corneum and results in abnormalities in the structure of lamellar bodies, the organelle which delivers lipid to the stratum corneum. In addition, the organization of secreted lamellar body material into lamellar bilayers within the stratum corneum interstices is disrupted by TOFA treatment. Finally, these abnormalities in lamellar body and stratum corneum membrane structure are corrected by coapplication of palmitate with TOFA. These results demonstrate a requirement for bulk fatty acids in barrier homeostasis. Thus, inhibiting the epidermal synthesis of any of the three key lipids that form the extracellular, lipid-enriched membranes of the stratum corneum results in an impairment in barrier homeostasis.

Fatty acids are required for epidermal permeability barrier function.

PubMed Central

Mao-Qiang, M; Elias, P M; Feingold, K R

1993-01-01

The permeability barrier is mediated by a mixture of ceramides, sterols, and free fatty acids arranged as extracellular lamellar bilayers in the stratum corneum. Whereas prior studies have shown that cholesterol and ceramides are required for normal barrier function, definitive evidence for the importance of nonessential fatty acids is not available. To determine whether epidermal fatty acid synthesis also is required for barrier homeostasis, we applied 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA), an inhibitor of acetyl CoA carboxylase, after disruption of the barrier by acetone or tape stripping. TOFA inhibits epidermal fatty acid by approximately 50% and significantly delays barrier recovery. Moreover, coadministration of palmitate with TOFA normalizes barrier recovery, indicating that the delay is due to a deficiency in bulk fatty acids. Furthermore, TOFA treatment also delays the return of lipids to the stratum corneum and results in abnormalities in the structure of lamellar bodies, the organelle which delivers lipid to the stratum corneum. In addition, the organization of secreted lamellar body material into lamellar bilayers within the stratum corneum interstices is disrupted by TOFA treatment. Finally, these abnormalities in lamellar body and stratum corneum membrane structure are corrected by coapplication of palmitate with TOFA. These results demonstrate a requirement for bulk fatty acids in barrier homeostasis. Thus, inhibiting the epidermal synthesis of any of the three key lipids that form the extracellular, lipid-enriched membranes of the stratum corneum results in an impairment in barrier homeostasis. Images PMID:8102380

Skin hydration: interplay between molecular dynamics, structure and water uptake in the stratum corneum.

PubMed

Mojumdar, Enamul Haque; Pham, Quoc Dat; Topgaard, Daniel; Sparr, Emma

2017-11-16

Hydration is a key aspect of the skin that influences its physical and mechanical properties. Here, we investigate the interplay between molecular and macroscopic properties of the outer skin layer - the stratum corneum (SC) and how this varies with hydration. It is shown that hydration leads to changes in the molecular arrangement of the peptides in the keratin filaments as well as dynamics of C-H bond reorientation of amino acids in the protruding terminals of keratin protein within the SC. The changes in molecular structure and dynamics occur at a threshold hydration corresponding to ca. 85% relative humidity (RH). The abrupt changes in SC molecular properties coincide with changes in SC macroscopic swelling properties as well as mechanical properties in the SC. The flexible terminals at the solid keratin filaments can be compared to flexible polymer brushes in colloidal systems, creating long-range repulsion and extensive swelling in water. We further show that the addition of urea to the SC at reduced RH leads to similar molecular and macroscopic responses as the increase in RH for SC without urea. The findings provide new molecular insights to deepen the understanding of how intermediate filament organization responds to changes in the surrounding environment.

Immediate and extended effects of sodium lauryl sulphate exposure on stratum corneum natural moisturizing factor.

PubMed

Hoffman, D R; Kroll, L M; Basehoar, A; Reece, B; Cunningham, C T; Koenig, D W

2014-02-01

Natural moisturizing factor (NMF) serves as the primary humectant of the stratum corneum (SC), principally comprised of hygroscopic amino acids and derivatives that absorb moisture. Barrier disruption has been shown to differentially affect the levels of specific NMF components, though the kinetics of NMF component restoration following disruption have not been examined. Here, we investigated the impact of barrier disruption caused by surfactant exposure on a subset of NMF components immediately following exposure and out to 10 days post-exposure. Volunteers wore patches containing either 1% w/v sodium lauryl sulphate (SLS) or distilled water on their forearms for 24 h. Measurements of transepidermal water loss, erythema, SC water content and a subset of SC NMF and lipid components were obtained at both sites before treatment, the day of patch removal, and 1, 2, 3, 6, and 10 days following treatment. Most measured NMF components decreased in response to SLS exposure. Exceptions were increases in lactate, ornithine and urea, and no difference in proline levels. In the days following exposure, reduced levels of several NMF components continued at the SLS site; however, all measured NMF components demonstrated equivalence to the vehicle control within 10 days. Histidine pH 7, lactate, ornithine and urea were the first to achieve levels equivalent to the vehicle control site, normalizing within 1 day after patch removal. Results imply that NMF components derived from sweat and urea cycling are least impacted by SLS exposure whereas NMF components derived from degradation of filaggrin and/or other S-100 proteins are most impacted. This implies the restoration of the processes responsible for S-100 protein processing into free amino acids takes several days to return to normal. Further examination of the enzymes involved in S-100 protein processing following barrier disruption would provide insight into the pathway(s) for NMF restoration during SC recovery. © 2013

Comparative distribution of sulphur, thiols and disulphides in the porcine stratum corneum.

PubMed

Meyer, W; Zschemisch, N H; Lehmann, H; Busche, R; Kunz, U

2005-01-01

Biochemical, histochemical and cytochemical analyses were used to determine the sulphur contents and the thiol and disulphide distribution in the stratum corneum (SC) of the wild boar (WB), a large domestic pig breed (DP) and the Goettingen miniature pig (GMP). The sulphur contents (% DW) were different in the three animal types (WB: 1.70-1.38 body, 0.54 ear; DP: 0.84-0.53 body, 0.50 ear; GMP: 2.28-2.51 body, 2.66 ear). The results of the histochemical analysis of SH- and -S-S- groups were clear, and densitometrical extinctions were highest in most body regions of the GMP for thiols and disulphides, followed by the DP for thiols, and the WB for disulphides. Absolute SC thickness was highest in the body of the GMP (62-80 mum), and generally lowest in the ear (20-38 mum) of all animal types. Relative SC thickness was the same for all animals in the body (40-66%), but lower in the ear (30%). Only -S-S- concentrations were correlated with SC thickness, and primarily in the GMP. Cytochemical analysis showed that high sulphur concentrations were obvious particularly in the CCE of corneal cells in the DP, as compared to the cytoplasm. Intracellular sulphur distribution was homogenous in the WB, and in the GMP, although in the latter at a higher concentration level. The results indicate breed-related effects on keratinisation in porcine corneal cells. Only the SC of the outer side of the ear of DP females is recommended as a model for humans.

Penetration of gold nanoparticles across the stratum corneum layer of thick-Skin.

PubMed

Raju, Gayathri; Katiyar, Neeraj; Vadukumpully, Sajini; Shankarappa, Sahadev A

2018-02-01

Transdermal particulate penetration across thick-skin, such as that of palms and sole, is particularly important for drug delivery for disorders such as small fiber neuropathies. Nanoparticle-based drug delivery across skin is believed to have much translational applications, but their penetration especially through thick-skin, is not clear. This study specifically investigates the effectiveness of gold nanoparticles (AuNPs) for thick-skin penetration, especially across the stratum corneum (SC) as a function of particle size. The thick-skinned hind-paw of rat was used to characterize depth and distribution of AuNPs of varying sizes, namely, 22±3, 105±11, and 186±20nm. Epidermal penetration of AuNPs was characterized both, in harvested skin from the hind-paw using a diffusion chamber, as well as in vivo. Harvested skin segments exposed to 22nm AuNPs for only 3h demonstrated higher penetration (p<0.05) as compared to the 105 and 186nm particles. In animal studies, hind-paw skin of adult rats exposed to AuNPs solution for the same time, demonstrated nanoparticles in blood on the 4th day, and histological analysis revealed AuNPs in epidermal layers just below the SC, with no apparent tissue response. We conclude that the thick-skin allows nanoparticle penetration and acts as a depot for release of AuNPs into circulation long after the initial exposure has ceased. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Transdermal delivery of biomacromolecules using lipid-like nanoparticles

NASA Astrophysics Data System (ADS)

Bello, Evelyn A.

The transdermal delivery of biomacromolecules, including proteins and nucleic acids, is challenging, owing to their large size and the penetration-resistant nature of the stratum corneum. Thus, an urgent need exists for the development of transdermal delivery methodologies. This research focuses on the use of cationic lipid-like nanoparticles (lipidoids) for the transdermal delivery of proteins, and establishes an in vitro model for the study. The lipidoids used were first combinatorially designed and synthesized; afterwards, they were employed for protein encapsulation in a vesicular system. A skin penetration study demonstrated that lipidoids enhance penetration depth in a pig skin model, overcoming the barrier that the stratum corneum presents. This research has successfully identified active lipidoids capable of efficiently penetrating the skin; therefore, loading proteins into lipidoid nanoparticles will facilitate the transdermal delivery of proteins. Membrane diffusion experiments were used to confirm the results. This research has confirmed that lipidoids are a suitable material for transdermal protein delivery enhancement.

Impact of the long chain omega-acylceramides on the stratum corneum lipid nanostructure. Part 1: Thermotropic phase behaviour of CER[EOS] and CER[EOP] studied using X-ray powder diffraction and FT-Raman spectroscopy.

PubMed

Kessner, Doreen; Brezesinski, Gerald; Funari, Sergio S; Dobner, Bodo; Neubert, Reinhard H H

2010-01-01

The stratum corneum (SC), the outermost layer of the mammalian skin, is the main skin barrier. Ceramides (CERs) as the major constituent of the SC lipid matrix are of particular interest. At the moment, 11 classes of CERs are identified, but the effect of each single ceramide species is still not known. Therefore in this article, the thermotropic behaviour of the long chain omega-acylceramides CER[EOS] and CER[EOP] was studied using X-ray powder diffraction and FT-Raman spectroscopy. It was found that the omega-acylceramides CER[EOS] and CER[EOP] do not show a pronounced polymorphism which is observed for shorter chain ceramides as a significant feature. The phase behaviour of both ceramides is strongly influenced by the extremely long acyl-chain residue. The latter has a much stronger influence compared with the structure of the polar head group, which is discussed as extremely important for the appearance of a rich polymorphism. Despite the strong influence of the long chain, the additional OH-group of the phyto-sphingosine type CER[EOP] influences the lamellar repeat distance and the chain packing. The less polar sphingosine type CER[EOS] is stronger influenced by the long acyl-chain residue. Hydration is necessary for the formation of an extended hydrogen-bonding network between the polar head groups leading to the appearance of a long-periodicity phase (LPP). In contrast, the more polar CER[EOP] forms the LPP with densely packed alkyl chains already in the dry state.

Relative uptake of minoxidil into appendages and stratum corneum and permeation through human skin in vitro.

PubMed

Grice, Jeffrey E; Ciotti, Susan; Weiner, Norman; Lockwood, Peter; Cross, Sheree E; Roberts, Michael S

2010-02-01

We examined uptake of the model therapeutic agent, minoxidil, into appendages, stratum corneum (SC), and through human skin, under the influence of different vehicles. Quantitative estimation of therapeutic drug deposition into all three areas has not previously been reported. Finite doses of minoxidil (2%, w/v) in formulations containing varying amounts of ethanol, propylene glycol (PG), and water (60:20:20, 80:20:0, and 0:80:20 by volume, respectively) were used. Minoxidil in SC (by tape stripping), appendages (by cyanoacrylate casting), and receptor fluid was determined by liquid scintillation counting. At early times (30 min, 2 h), ethanol-containing formulations (60:20:20 and 80:20:0) caused significantly greater minoxidil retention in SC and appendages, compared to the formulation lacking ethanol (0:80:20). A significant increase in minoxidil receptor penetration occurred with the PG-rich 0:80:20 formulation after 12 h. We showed that deposition of minoxidil into appendages, SC, and skin penetration into receptor fluid were similar in magnitude. Transport by the appendageal route is likely to be a key determinant of hair growth promotion by minoxidil. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association.

Ethnic differences in stratum corneum functions between Chinese and Thai infants residing in Bangkok, Thailand.

PubMed

Fujimura, Tsutomu; Miyauchi, Yuki; Shima, Kyoko; Hotta, Mitsuyuki; Tsujimura, Hisashi; Kitahara, Takashi; Takema, Yoshinori; Palungwachira, Pakhawadee; Laohathai, Diane; Chanthothai, Jetchawa; Nararatwanchai, Thamthiwat

2018-01-01

Ethnic and racial differences in infant skin have not been well characterized. The purpose of this study was to establish whether there are ethnic differences and similarities in the stratum corneum (SC) functions of Thai and Chinese infants. Healthy infants 6 to 24 months of age (N = 60; 30 Thai, 30 Chinese) who resided in Bangkok, Thailand, were enrolled. Transepidermal water loss (TEWL) and SC hydration (capacitance) on the thigh, buttock, and upper arm were measured. Ceramide content was determined in the SC on the upper arm. SC hydration was not remarkably different between the two ethnicities at any site measured, but TEWL was significantly higher in Chinese infants than in Thai infants at all sites. Hydration of the SC was not significantly correlated with age in either ethnicity. TEWL had significant but weak correlations with age on the thigh and upper arm in Thai infants. Ceramide content was significantly higher in Chinese SC than in Thai SC. No relationship between ceramide content and TEWL or hydration was observed in either ethnicity. The significant differences in TEWL and ceramide contents between Chinese and Thai infant skin could prove useful in designing skin care and diapering products that are best suited for each ethnicity. © 2017 Wiley Periodicals, Inc.

Effect of Exercise-induced Sweating on facial sebum, stratum corneum hydration, and skin surface pH in normal population.

PubMed

Wang, Siyu; Zhang, Guirong; Meng, Huimin; Li, Li

2013-02-01

Evidence demonstrated that sweat was an important factor affecting skin physiological properties. We intended to assess the effects of exercise-induced sweating on the sebum, stratum corneum (SC) hydration and skin surface pH of facial skin. 102 subjects (aged 5-60, divided into five groups) were enrolled to be measured by a combination device called 'Derma Unit SSC3' in their frontal and zygomatic regions when they were in a resting state (RS), at the beginning of sweating (BS), during excessive sweating (ES) and an hour after sweating (AS), respectively. Compared to the RS, SC hydration in both regions increased at the BS or during ES, and sebum increased at the BS but lower during ES. Compared to during ES, Sebum increased in AS but lower than RS. Compared to the RS, pH decreased in both regions at the BS in the majority of groups, and increased in frontal region during ES and in zygomatic region in the AS. There was an increase in pH in both regions during ES in the majority of groups compared to the BS, but a decrease in the AS compared to during ES. The study implies that even in summer, after we sweat excessively, lipid products should be applied locally in order to maintain stability of the barrier function of the SC. The study suggests that after a short term(1 h or less) of self adjustment, excessive sweat from moderate exercise will not impair the primary acidic surface pH of the facial skin. Exercise-induced sweating significantly affected the skin physiological properties of facial region. © 2012 John Wiley & Sons A/S.

The Rheological Properties of Lipid Monolayers Modulate the Incorporation of l-Ascorbic Acid Alkyl Esters.

PubMed

Díaz, Yenisleidy de Las Mercedes Zulueta; Mottola, Milagro; Vico, Raquel V; Wilke, Natalia; Fanani, María Laura

2016-01-19

In this work, we tested the hypothesis that the incorporation of amphiphilic drugs into lipid membranes may be regulated by their rheological properties. For this purpose, two members of the l-ascorbic acid alkyl esters family (ASCn) were selected, ASC16 and ASC14, which have different rheological properties when organized at the air/water interface. They are lipophilic forms of vitamin C used in topical pharmacological preparations. The effect of the phase state of the host lipid membranes on ASCn incorporation was explored using Langmuir monolayers. Films of pure lipids with known phase states have been selected, showing liquid-expanded, liquid-condensed, and solid phases as well as pure cholesterol films in liquid-ordered state. We also tested ternary and quaternary mixed films that mimic the properties of cholesterol containing membranes and of the stratum corneum. The compressibility and shear properties of those monolayers were assessed in order to define its phase character. We found that the length of the acyl chain of the ASCn compounds induces differential changes in the rheological properties of the host membrane and subtly regulates the kinetics and extent of the penetration process. The capacity for ASCn uptake was found to depend on the phase state of the host film. The increase in surface pressure resultant after amphiphile incorporation appears to be a function of the capacity of the host membrane to incorporate such amphiphile as well as the rheological response of the film. Hence, monolayers that show a solid phase state responded with a larger surface pressure increase to the incorporation of a comparable amount of amphiphile than liquid-expanded ones. The cholesterol-containing films, including the mixture that mimics stratum corneum, allowed a very scarce ASCn uptake independently of the membrane diffusional properties. This suggests an important contribution of Cho on the maintenance of the barrier function of stratum corneum.

Variations in the ceramide profile in different seasons and regions of the body contribute to stratum corneum functions.

PubMed

Ishikawa, Junko; Shimotoyodome, Yoshie; Ito, Shotaro; Miyauchi, Yuki; Fujimura, Tsutomu; Kitahara, Takashi; Hase, Tadashi

2013-03-01

The objective of this study was to clarify variations of the ceramide (CER) profile in human stratum corneum (SC) in different seasons and in different regions of the body and to estimate the contributions of CERs to the SC barrier and water-holding functions. Based on the information that there are great variations of SC functions among body sites, we compared the CER profiles obtained from ten different anatomical sites in healthy Japanese males in four seasons. Not only the physiological parameters of skin but also the CER profile showed body region and seasonal variations. The total CER level, the CER composition and the C34-CER[NS] species displayed strong correlations with the values of transepidermal water loss and capacitance throughout the body. Especially in the cheek, a strong correlation between the capacitance and the CER profile was observed. There were seasonal variations of the CER profile in the lip, upper arm and palm. Our results indicate that regional and seasonal variations of the CER profile may contribute to SC functions.

Scalp stratum corneum histamine levels: novel sampling method reveals association with itch resolution in dandruff/seborrhoeic dermatitis treatment.

PubMed

Kerr, Kathy; Schwartz, James R; Filloon, Thomas; Fieno, Angela; Wehmeyer, Ken; Szepietowski, Jacek C; Mills, Kevin J

2011-06-01

Dandruff and seborrhoeic dermatitis are accompanied by bothersome itch. We have established a novel non-invasive methodology to sample histamine levels in the stratum corneum in order to facilitate an understanding of pruritogenesis in this condition. Histamine levels were assessed in two groups of subjects with dandruff before and after 3 weeks of treatment with a commercial potentiated zinc pyrithione shampoo. A comparative population without dandruff was also studied. Itch self-perception was quantified on a visual analogue scale. The histamine level in subjects with dandruff was more than twice that in those who did not have dandruff. Under conditions known to resolve flaking symptoms, the shampoo led to a reduction in histamine in subjects with dandruff to a level that was statistically indistinguishable from those who did not have dandruff. This reduction in histamine was accompanied by a highly significant reduction in the perception of itch intensity. These findings suggest an association between the subjective perception of itch in the scalp and the level of histamine in the skin.

Comparison of protocols measuring diffusion and partition coefficients in the stratum corneum

PubMed Central

Rothe, H.; Obringer, C.; Manwaring, J.; Avci, C.; Wargniez, W.; Eilstein, J.; Hewitt, N.; Cubberley, R.; Duplan, H.; Lange, D.; Jacques‐Jamin, C.; Klaric, M.; Schepky, A.

2017-01-01

Abstract Partition (K) and diffusion (D) coefficients are important to measure for the modelling of skin penetration of chemicals through the stratum corneum (SC). We compared the feasibility of three protocols for the testing of 50 chemicals in our main studies, using three cosmetics‐relevant model chemicals with a wide range of logP values. Protocol 1: SC concentration‐depth profile using tape‐stripping (measures KSC/v and DSC/HSC 2, where HSC is the SC thickness); Protocol 2A: incubation of isolated SC with chemical (direct measurement of KSC/v only) and Protocol 2B: diffusion through isolated SC mounted on a Franz cell (measures KSC/v and DSC/HSC 2, and is based on Fick's laws). KSC/v values for caffeine and resorcinol using Protocol 1 and 2B were within 30% of each other, values using Protocol 2A were ~two‐fold higher, and all values were within 10‐fold of each other. Only indirect determination of KSC/v by Protocol 2B was different from the direct measurement of KSC/v by Protocol 2A and Protocol 1 for 7‐EC. The variability of KSC/v for all three chemicals using Protocol 2B was higher compared to Protocol 1 and 2A. DSC/HSC 2 values for the three chemicals were of the same order of magnitude using all three protocols. Additionally, using Protocol 1, there was very little difference between parameters measured in pig and human SC. In conclusion, KSC/v, and DSC values were comparable using different methods. Pig skin might be a good surrogate for human skin for the three chemicals tested. Copyright © 2017 The Authors Journal of Applied Toxicology published by John Wiley & Sons Ltd. PMID:28139006

The use of D-optimal mixture design in optimising okara soap formulation for stratum corneum application.

PubMed

Borhan, Farrah Payyadhah; Abd Gani, Siti Salwa; Shamsuddin, Rosnah

2014-01-01

Okara, soybean waste from tofu and soymilk production, was utilised as a natural antioxidant in soap formulation for stratum corneum application. D-optimal mixture design was employed to investigate the influence of the main compositions of okara soap containing different fatty acid and oils (virgin coconut oil A (24-28% w/w), olive oil B (15-20% w/w), palm oil C (6-10% w/w), castor oil D (15-20% w/w), cocoa butter E (6-10% w/w), and okara F (2-7% w/w)) by saponification process on the response hardness of the soap. The experimental data were utilized to carry out analysis of variance (ANOVA) and to develop a polynomial regression model for okara soap hardness in terms of the six design factors considered in this study. Results revealed that the best mixture was the formulation that included 26.537% A, 19.999% B, 9.998% C, 16.241% D, 7.633% E, and 7.000% F. The results proved that the difference in the level of fatty acid and oils in the formulation significantly affects the hardness of soap. Depending on the desirable level of those six variables, creation of okara based soap with desirable properties better than those of commercial ones is possible.

Sun-induced changes of stratum corneum hydration vary with age and gender in a normal Chinese population.

PubMed

Liu, Zhili; Song, Shunpeng; Luo, Wenhai; Elias, Peter M; Man, Mao-Qiang

2012-02-01

Previous studies have demonstrated that sun-induced alteration of epidermal permeability barrier function varies with gender and age. In the present study, we assess the stratum corneum (SC) hydration in sun-exposed males and females. A total of 168 subjects (84 males and 84 females) aged 19-75 years were enrolled. A multifunctional skin physiology monitor was used to measure SC hydration. In comparison with non-sun exposure, sun exposure does not cause a significant change in SC hydration in either young males or young females, whereas in aged females, a significant reduction of SC hydration is seen on the forehead and the dorsal hand of sun-exposed subjects. SC hydration on the canthus of both aged males and aged females is significantly lower than that of young subjects. Additionally, SC hydration on the dorsal hand of aged females is also significantly lower as compared with young females. Sun-induced reduction of SC hydration is more evident on the dorsal hand of aged females than that of males (P<0.001). Moreover, the SC rehydration capacity is significantly lower in sun-exposed aged females than in age-matched males. These results demonstrated that sun-induced changes of the SC hydration property vary with age and gender. © 2011 John Wiley & Sons A/S.

The Use of D-Optimal Mixture Design in Optimising Okara Soap Formulation for Stratum Corneum Application

PubMed Central

Borhan, Farrah Payyadhah; Abd Gani, Siti Salwa; Shamsuddin, Rosnah

2014-01-01

Okara, soybean waste from tofu and soymilk production, was utilised as a natural antioxidant in soap formulation for stratum corneum application. D-optimal mixture design was employed to investigate the influence of the main compositions of okara soap containing different fatty acid and oils (virgin coconut oil A (24–28% w/w), olive oil B (15–20% w/w), palm oil C (6–10% w/w), castor oil D (15–20% w/w), cocoa butter E (6–10% w/w), and okara F (2–7% w/w)) by saponification process on the response hardness of the soap. The experimental data were utilized to carry out analysis of variance (ANOVA) and to develop a polynomial regression model for okara soap hardness in terms of the six design factors considered in this study. Results revealed that the best mixture was the formulation that included 26.537% A, 19.999% B, 9.998% C, 16.241% D, 7.633% E, and 7.000% F. The results proved that the difference in the level of fatty acid and oils in the formulation significantly affects the hardness of soap. Depending on the desirable level of those six variables, creation of okara based soap with desirable properties better than those of commercial ones is possible. PMID:25548777

The morphologic changes in lamellar bodies and intercorneocyte lipids after tape stripping and occlusion with a water vapor-impermeable membrane.

PubMed

Jiang, S; Koo, S W; Lee, S H

1998-03-01

It has been reported that artificial restoration of barrier function by a water vapor-impermeable membrane after tape stripping induces barrier abrogation in hairless mice, impeding rather than enhancing barrier recovery. To address this issue, we examined the morphologic changes in the epidermis after tape stripping and occlusion with a water vapor-impermeable membrane in murine skin. Male hairless mice were used for all studies of barrier perturbation and occlusion. Barrier disruption was achieved by repeated application of cellophane tape. Immediately after tape stripping the animals were wrapped in a tightly fitting water vapor-impermeable membrane. Transepidermal water loss (TEWL) was measured 20 min after tape stripping and 14, 24, 36, 48 and 60 h after occlusion. For electron microscopy the samples were treated with osmium tetroxide (OsO4) or ruthenium tetroxide (RuO4). When tape-stripped animals were wrapped in a water vapor-impermeable membrane, thereby preventing water flux, barrier function did not recover normally. These results demonstrate that an artificial block to TEWL with an impermeable membrane did not enhance barrier recovery. By electron microscopy many transitional cells and lacunae of various sizes were seen within the intercellular spaces of the stratum corneum after occlusion following tape stripping. Occlusion also caused alterations in both lipid lamellar membrane structures in the stratum corneum interstices and the lamellar bodies in the cytosol of granulocytes and transitional cells. Secreted lamellar body contents also appeared to be abnormal in the stratum corneum-stratum granulosum junction.

Encapsulation of the UV filters ethylhexyl methoxycinnamate and butyl methoxydibenzoylmethane in lipid microparticles: effect on in vivo human skin permeation.

PubMed

Scalia, S; Mezzena, M; Ramaccini, D

2011-01-01

Lipid microparticles loaded with the UVB filter ethylhexyl methoxycinnamate (EHMC) and the UVA filter butyl methoxydibenzoylmethane (BMDBM) were evaluated for their effect on the sunscreen agent's percutaneous penetration. Microparticles loaded with EHMC or BMDBM were prepared by the melt emulsification technique using stearic acid or glyceryl behenate as lipidic material, respectively, and hydrogenate phosphatidylcholine as the surfactant. Nonencapsulated BMDBM and EHMC in conjunction with blank microparticles or equivalent amounts of the 2 UV filters loaded in the lipid microparticles were introduced into oil-in-water emulsions and applied to human volunteers. Skin penetration was investigated in vivo by the tape-stripping technique. For the cream with the nonencapsulated sunscreen agents, the percentages of the applied dose diffused into the stratum corneum were 32.4 ± 4.1% and 30.3 ± 3.3% for EHMC and BMDBM, respectively. A statistically significant reduction in the in vivo skin penetration to 25.3 ± 5.5% for EHMC and 22.7 ± 5.4% for BMDBM was achieved by the cream containing the microencapsulated UV filters. The inhibiting effect on permeation attained by the lipid microparticles was more marked (45-56.3% reduction) in the deeper stratum corneum layers. The reduced percutaneous penetration of BMDBM and EHMC achieved by the lipid microparticles should preserve the UV filter efficacy and limit potential toxicological risks. Copyright © 2011 S. Karger AG, Basel.

Investigation of a CER[NP]- and [AP]-Based Stratum Corneum Modeling Membrane System: Using Specifically Deuterated CER Together with a Neutron Diffraction Approach.

PubMed

Schmitt, Thomas; Lange, Stefan; Dobner, Bodo; Sonnenberger, Stefan; Hauß, Thomas; Neubert, Reinhard H H

2018-01-30

Neutron diffraction was used as a tool to investigate the lamellar as well as molecular nanostructure of ceramide-[NP]/ceramide-[AP]/cholesterol/lignoceric acid model systems with a nativelike 2:1 ratio and a 1:2 ratio to study the influence of the ceramide-[AP]. By using mixtures together with cholesterol and free fatty acids as well as a humidity and temperature chamber while measuring, natural conditions were simulated as closely as possible. Despite its simplicity, the system simulated the native stratum corneum lipid matrix fairly closely, showing a similar lamellar thickness with a repeat distance of 5.45 ± 0.1 nm and a similar arrangement with overlapping long C24 chains. Furthermore, despite the very minor chemical difference between ceramide-[NP] and ceramide-[AP], which is only a single OH group, it was possible to demonstrate substantial differences between the structural influence of the two ceramides. Ceramide-[AP] could be concluded to be arranged in such a way that its C24 chain in both ratios is somehow shorter than that of ceramide-[NP], not overlapping as much with the opposite lamellar leaflet. Furthermore, in the unnatural 1:2 ratio, the higher ceramide-[AP] content causes an increased tilt of the ceramide acyl chains. This leads to even less overlapping within the lamellar midplane, whereas the repeat distance stays the same as for the ceramide-[NP]-rich system. In this nativelike 2:1 ratio, the chains are arranged mostly straight, and the long C24 chains show a broad overlapping region in the lamellar midplane.

Confocal Raman microspectroscopy of stratum corneum: a pre-clinical validation study.

PubMed

Wu, J; Polefka, T G

2008-02-01

Skin moisturization is not only important for maintaining skin functional properties but also has great impact on the skin's aesthetic properties. The top layer of the skin, the stratum corneum (SC), plays a key role in protecting and preventing against external aggressions as well as in regulating water flux in and out. Confocal Raman microspectroscopy is the first commercially available technique that provides a non-invasive, in vivo method to determine depth profiles of water concentration in the skin, however, in this case it was applied in an in vitro setting. As the first phase of validating the usefulness of confocal Raman microspectroscopy, we used porcine skin as a surrogate for human skin. Water concentration profiles were obtained using confocal Raman microspectroscopy from isolated pigskin SC and compared with that using the Karl Fischer titration method. The two methods correlated very well with a regression coefficient of 1.07 as well as a correlation coefficient, R(2) = 0.989, which demonstrated the consistency and accuracy of confocal Raman microspectroscopy for water concentration determination. To evaluate the instrument's response to different skin care/cleansing products, a wide range of products were tested to compare their skin moisturization ability. Among those tested were a lotion, commercial soap bar, syndet bar, traditional non-emollient shower gel (water, Sodium Laureth Ether Sulfate (SLES), cocamidopropyl betaine system) and emollient containing shower gel (water, sunflower oil, SLES, cocamidopropyl betaine, glycerin, petrolatum). The results were consistent with what was expected. The water content on skin treated with (A) lotion was significantly higher than the non-treated control; (B) syndet bar-treated skin had a significantly higher water content than soap-based bar-treated sites; (C) non-emollient shower gel washed sites were more moisturized than soap-based bar-treated samples; and (D) emollient shower gel-treated skin was

Comparison of protocols measuring diffusion and partition coefficients in the stratum corneum.

PubMed

Rothe, H; Obringer, C; Manwaring, J; Avci, C; Wargniez, W; Eilstein, J; Hewitt, N; Cubberley, R; Duplan, H; Lange, D; Jacques-Jamin, C; Klaric, M; Schepky, A; Grégoire, S

2017-07-01

Partition (K) and diffusion (D) coefficients are important to measure for the modelling of skin penetration of chemicals through the stratum corneum (SC). We compared the feasibility of three protocols for the testing of 50 chemicals in our main studies, using three cosmetics-relevant model chemicals with a wide range of logP values. Protocol 1: SC concentration-depth profile using tape-stripping (measures K SC/v and D SC /H SC 2 , where H SC is the SC thickness); Protocol 2A: incubation of isolated SC with chemical (direct measurement of K SC/v only) and Protocol 2B: diffusion through isolated SC mounted on a Franz cell (measures K SC/v and D SC /H SC 2 , and is based on Fick's laws). K SC/v values for caffeine and resorcinol using Protocol 1 and 2B were within 30% of each other, values using Protocol 2A were ~two-fold higher, and all values were within 10-fold of each other. Only indirect determination of K SC/v by Protocol 2B was different from the direct measurement of K SC/v by Protocol 2A and Protocol 1 for 7-EC. The variability of K SC/v for all three chemicals using Protocol 2B was higher compared to Protocol 1 and 2A. D SC /H SC 2 values for the three chemicals were of the same order of magnitude using all three protocols. Additionally, using Protocol 1, there was very little difference between parameters measured in pig and human SC. In conclusion, K SC/v, and D SC values were comparable using different methods. Pig skin might be a good surrogate for human skin for the three chemicals tested. Copyright © 2017 The Authors Journal of Applied Toxicology published by John Wiley & Sons Ltd. Copyright © 2017 The Authors Journal of Applied Toxicology published by John Wiley & Sons Ltd.

Investigation of cis-trans isomer dependent dermatotoxicokinetics of UV filter ethylhexyl methoxycinnamate through stratum corneum in vivo.

PubMed

Sharma, Anežka; Bányiová, Katarína; Vrana, Branislav; Justan, Ivan; Čupr, Pavel

2017-11-01

2-Ethylhexyl methoxycinnamate (EHMC) is one of the most used ultraviolet filters in personal care products. It undergoes cis/trans isomerization in sunlight, and there is limited toxicological understanding of the effects of the cis-isomer. It is known that two geometric isomers of one compound can have different physico-chemical properties and effects. However, there are no studies focusing on toxicokinetics of EHMC isomerization products to compare their potential difference in dermal exposure to cis-EHMC and trans-EHMC due to the difference in their dermatotoxicokinetics. In this study, dermal absorption of the parental trans-EHMC and its cis isomer was studied. A commercially available sunscreen lotion containing trans-EHMC and spiked with laboratory-prepared cis-EHMC was locally applied on the forearm skin of two volunteers. After 8 h of skin exposure, the stratum corneum (SC) layer was removed by tape stripping. The removed thickness of the SC was determined spectrophotometrically using a total protein assay. The concentration of both isomers in the removed SC was measured by HPLC-DAD. A new diffusion and permeability coefficient of both EHMC isomers in SC were determined by Fick's second law of diffusion in vivo. The difference in dermatotoxicokinetic parameters between the two isomers was not statistically significant. However, separate toxicological studies of isomeric forms and the determination of their dermatotoxicokinetic parameters are crucial for refinement of human risk assessment.

Sun-Induced Changes in Stratum Corneum Function Are Gender and Dose Dependent in a Chinese Population

PubMed Central

Liu, Z.; Fluhr, J.W.; Song, S.P.; Sun, Z.; Wang, H.; Shi, Y.J.; Elias, P.M.; Man, M.-Q.

2010-01-01

Previous studies have demonstrated that UVB radiation changes the epidermal permeability barrier and stratum corneum (SC) hydration. It is well known that sun exposure causes erythema, sunburn and melanoma. However, whether daily sun exposure alters SC integrity and epidermal permeability barrier function is largely unknown, especially in Chinese subjects. In the present study, we assess the SC integrity, SC hydration and epidermal permeability barrier function following various doses of sun exposure. A total of 258 subjects (124 males and 134 females) aged 18–50 years were enrolled. A multifunctional skin physiology monitor (Courage & Khazaka MPA5) was used to measure SC hydration and transepidermal water loss (TEWL) on the forearms. In males, basal TEWL was higher with higher doses of sun exposure than with lower doses and control, whereas in females, basal TEWL was higher with lower doses of sun exposure than with higher doses and control. In the group with higher doses of sun exposure, TEWL in females was significantly lower than that in males. The barrier recovery was faster in females than in males in both control and lower-dose groups. In both males and females, barrier recovery was delayed with higher doses of sun exposure. In males, sun exposure did not alter SC hydration, while in females SC hydration was lower with lower doses of sun exposure as compared with control and higher doses of sun exposure. These results demonstrated that sun-induced changes in SC function and SC hydration vary with gender and the extent of sun exposure. PMID:20571289

Properties of Skin in Chinese Infants: Developmental Changes in Ceramides and in Protein Secondary Structure of the Stratum Corneum

PubMed Central

Yuan, Chao; Zou, Ying; Xueqiu, Yao; Miyauchi, Yuki; Fujimura, Tsutomu; Kitahara, Takashi; Wang, Xuemin

2017-01-01

The properties of infant skin regarding its structure and stratum corneum (SC) properties during development compared to adult skin have been reported only for a few races and body sites. The aim of this study was to understand the developmental changes of skin properties in Chinese infants, focusing on SC ceramides and protein secondary structure, which are important for skin barrier function. Three body sites with distinct characteristics (cheeks, inner upper arms, and buttocks) were assessed. Sixty pairs of Chinese infants and their mothers were measured for SC hydration, transepidermal water loss, ceramide levels, sebum with an ester bond, and protein secondary structure of superficial SC. Skin hydration decreased with age at all body sites. TEWL was similar between the 2–12- and 13–24-month-old groups but was higher than the adult group at the buttocks and inner upper arms and was equal to the adult group at the cheeks. These differences coincided with differences in protein secondary structure. Ceramide and sebum levels were lower in the infant groups. We conclude that both the SC functions and the components of infant skin are still developing and are not fully adapted as in adult skin at each body site examined. PMID:29098152

Status of surfactants as penetration enhancers in transdermal drug delivery

PubMed Central

Som, Iti; Bhatia, Kashish; Yasir, Mohd.

2012-01-01

Surfactants are found in many existing therapeutic, cosmetic, and agro-chemical preparations. In recent years, surfactants have been employed to enhance the permeation rates of several drugs via transdermal route. The application of transdermal route to a wider range of drugs is limited due to significant barrier to penetration across the skin which is associated with the outermost stratum corneum layer. Surfactants have effects on the permeability characteristics of several biological membranes including skin. They have the potential to solubilize lipids within the stratum corneum. The penetration of the surfactant molecule into the lipid lamellae of the stratum corneum is strongly dependent on the partitioning behavior and solubility of surfactant. Surfactants ranging from hydrophobic agents such as oleic acid to hydrophilic sodium lauryl sulfate have been tested as permeation enhancer to improve drug delivery. This article reviews the status of surfactants as permeation enhancer in transdermal drug delivery of various drugs. PMID:22368393

Influence of multiple light-scattering on TiO2 nanoparticles imbedded into stratum corneum on light transmittance in UV and visible wavelength regions

NASA Astrophysics Data System (ADS)

Popov, Alexey P.; Priezzhev, Alexander V.; Lademann, Jürgen; Myllylä, Risto

2007-05-01

This paper focuses on the simulation of propagation of radiation in UV and visible wavelength regions within a superficial skin layer (stratum corneum, SC) partially filled with titanium dioxide (TiO II) nanoparticles. Volume concentrations of the particles (0.67% - 2.25%) correspond to the maximal concentrations of the considered particles in the frames of independent scattering. Transmittance of 307-, 400-, and 500-nm light through a 20-μm thick SC is calculated. The effect of the TiO II nanoparticles on the contribution of photons undergone different numbers of scattering acts into transmittance is considered. It is shown that administration of the nanoparticles results in the broadening of the distribution of transmitted photons over undergone scattering acts. It also results in the shift of the maximum location of this distribution to larger number of scattering acts for the wavelengths of 400 and 500 nm being the latter the most pronounced. The increase of undergone scattering acts leads to the elongation of photon trajectories within the medium and results in the increase of the diffuse reflected light and the transmittance decrease.

Cutaneous water loss and sphingolipids in the stratum corneum of house sparrows, Passer domesticus L., from desert and mesic environments as determined by reversed phase high-performance liquid chromatography coupled with atmospheric pressure photospray ionization mass spectrometry.

PubMed

Muñoz-Garcia, Agustí; Ro, Jennifer; Brown, Johnie C; Williams, Joseph B

2008-02-01

Because cutaneous water loss (CWL) represents half of total water loss in birds, selection to reduce CWL may be strong in desert birds. We previously found that CWL of house sparrows from a desert population was about 25% lower than that of individuals from a mesic environment. The stratum corneum (SC), the outer layer of the epidermis, serves as the primary barrier to water vapor diffusion through the skin. The avian SC is formed by layers of corneocytes embedded in a lipid matrix consisting of cholesterol, free fatty acids and two classes of sphingolipids, ceramides and cerebrosides. The SC of birds also serves a thermoregulatory function; high rates of CWL keep body temperatures under lethal limits in episodes of heat stress. In this study, we used high-performance liquid chromatography coupled with atmospheric pressure photoionization-mass spectrometry (HPLC/APPI-MS) to identify and quantify over 200 sphingolipids in the SC of house sparrows from desert and mesic populations. Principal components analysis (PCA) led to the hypotheses that sphingolipids in the SC of desert sparrows have longer carbon chains in the fatty acid moiety and are more polar than those found in mesic sparrows. We also tested the association between principal components and CWL in both populations. Our study suggested that a reduction in CWL found in desert sparrows was, in part, the result of modifications in chain length and polarity of the sphingolipids, changes that apparently determine the interactions of the lipid molecules within the SC.

Free fatty acids chain length distribution affects the permeability of skin lipid model membranes.

PubMed

Uchiyama, Masayuki; Oguri, Masashi; Mojumdar, Enamul H; Gooris, Gert S; Bouwstra, Joke A

2016-09-01

The lipid matrix in the stratum corneum (SC) plays an important role in the barrier function of the skin. The main lipid classes in this lipid matrix are ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs). The aim of this study was to determine whether a variation in CER subclass composition and chain length distribution of FFAs affect the permeability of this matrix. To examine this, we make use of lipid model membranes, referred to as stratum corneum substitute (SCS). We prepared SCS containing i) single CER subclass with either a single FFA or a mixture of FFAs and CHOL, or ii) a mixture of various CER subclasses with either a single FFA or a mixture of FFAs and CHOL. In vitro permeation studies were performed using ethyl-p-aminobenzoic acid (E-PABA) as a model drug. The flux of E-PABA across the SCS containing the mixture of FFAs was higher than that across the SCS containing a single FA with a chain length of 24 C atoms (FA C24), while the E-PABA flux was not effected by the CER composition. To select the underlying factors for the changes in permeability, the SCSs were examined by Fourier transform infrared spectroscopy (FTIR) and Small angle X-ray scattering (SAXS). All lipid models demonstrated a similar phase behavior. However, when focusing on the conformational ordering of the individual FFA chains, the shorter chain FFA (with a chain length of 16, 18 or 20 C atoms forming only 11m/m% of the total FFA level) had a higher conformational disordering, while the conformational ordering of the chains of the CER and FA C24 and FA C22 hardly did not change irrespective of the composition of the SCS. In conclusion, the conformational mobility of the short chain FFAs present only at low levels in the model SC lipid membranes has a great impact on the permeability of E-PABA. Copyright © 2016 Elsevier B.V. All rights reserved.

Stratum corneum profiles of inflammatory mediators in patch test reactions to common contact allergens and sodium lauryl sulfate.

PubMed

Koppes, S A; Ljubojevic Hadzavdic, S; Jakasa, I; Franceschi, N; Jurakić Tončić, R; Marinović, B; Brans, R; Gibbs, S; Frings-Dresen, M H W; Rustemeyer, T; Kezic, S

2017-06-01

Recent studies have demonstrated allergen-specific differences in the gene expression of inflammatory mediators in patch tested skin. To determine levels of various inflammatory mediators in the stratum corneum (SC) after patch testing with common contact allergens and the skin irritant sodium lauryl sulfate (SLS). In total, 27 individuals who had previously patch tested positive to nickel, chromium, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) or para-phenylenediamine were retested and then patch tested with SLS and petrolatum, with petrolatum serving as the patch test control. At 72 h, the test sites were clinically graded and the SC samples collected on adhesive tape. The levels of 18 of the 32 quantified mediators differed significantly from that of the control patches for at least one of the tested substances. SLS and MCI/MI induced the largest number of immunomediators. Interleukin (IL)-16 levels were significantly higher in patch test reactions in all allergens than they were in the controls, while no significant difference was detected for SLS. Furthermore, a strong negative correlation was found between strength of patch test reaction and IL-1α levels. Cytokine profiles in the SC of patch tested skin did not show a distinct allergen-specific pattern. However, MCI/MI induced a larger and wider immune response than the other allergens, perhaps due to its potency as an irritant. The levels of IL-16 were significantly increased in patch test reactions to allergens but not to SLS; thus, they may help clinicians to differentiate between allergic contact dermatitis and irritant contact dermatitis. © 2016 British Association of Dermatologists.

Influence of niacinamide containing formulations on the molecular and biophysical properties of the stratum corneum.

PubMed

Mohammed, D; Crowther, J M; Matts, P J; Hadgraft, J; Lane, M E

2013-01-30

Niacinamide-containing moisturisers are known be efficacious in alleviating dry skin conditions and improving stratum corneum (SC) barrier function. However, the mechanisms of action of niacinamide at the molecular level in the SC are still not well understood. Previously, we have reported the development of novel methods to probe SC barrier properties in vivo. The aim of the present study was to characterise changes in Trans Epidermal Water Loss (TEWL), corneocyte surface area and maturity, selected protease activities and SC thickness after repeated application of a simple vehicle containing niacinamide. A commercial formulation was also included as a reference. The left and right mid-volar forearms of 20 healthy volunteers were used as study sites, to which topical formulations were applied twice daily for 28 days. After successive tape-stripping, corneocyte maturity and surface area were assessed. In addition, activity of the desquamatory kallikrein (KLK) protease enzymes KLK5 and KLK7, and tryptase and plasmin (implicated in inflammatory process) were measured using a fluorogenic probe assay. The amount of protein removed and TEWL were also recorded. SC thickness before and after treatment was determined using Confocal Raman Spectroscopy (CRS). Overall (i) corneocyte maturity and surface area decreased with increasing number of tape strips, (ii) activity of both the desquamatory and inflammatory enzymes was highest in the outer layers of the SC and decreased with depth (iii) TEWL increased as more SC layers were removed. Furthermore, areas treated with formulations containing niacinamide were significantly different to pre-treatment baseline and untreated/vehicle-control treated sites, with larger and more mature corneocytes, decreased inflammatory activity, decreased TEWL and increased SC thickness. These data (a) confirm the utility of measures and metrics developed previously for the non-invasive assay of SC barrier function, (b) present an holistic picture

Isolated human/animal stratum corneum as a partial model for 15 steps in percutaneous absorption: emphasizing decontamination, Part I.

PubMed

Hui, Xiaoying; Lamel, Sonia; Qiao, Peter; Maibach, Howard I

2013-03-01

Since the advent of World War II, governments and laboratories have made a concerted effort to improve prophylactic and therapeutic interventions counteracting cutaneously directed chemical warfare agents (CWA), and by inference, common industrial and consumer dermatotoxicants. In vitro percutaneous penetration assays, first utilized by Tregear in the 1940s and presently in various modifications, have been fundamental to this effort. Percutaneous penetration, often considered a simple one-step diffusion process, consists of at least 15 steps. The first part of this review covers the initial steps related to absorption and excretion kinetics, vehicle characteristics, and tissue disposition. Importantly, the partitioning behavior and stratum corneum (SC) diffusion by a wide physicochemical array of compounds shows that many compounds have similar diffusion coefficients determining their percutaneous absorption in vivo. After accounting for anatomical SC variation, the penetration flux value of a substance depends mainly on its SC/vehicle partition coefficient. Additionally, the SC acts as a 'reservoir' for topically applied molecules and application of tape stripping has been found to quantify the chemical remaining in the SC which can predict total molecular penetration in vivo. Decontamination is of particular concern and even expediting standard washing procedures after dermal chemical exposure often fails to remove chemicals. This overview summarizes knowledge of percutaneous penetration extending insights into the complexities of penetration, decontamination and potential newer assays that may be of practical importance. Copyright © 2012 John Wiley & Sons, Ltd.

Evaluation of skin surface hydration state and barrier function of stratum corneum of dorsa of hands and heels treated with PROTECT X2 skin protective cream.

PubMed

Kubota, Takahiro

2012-06-01

Skin roughness is a term commonly used in Japan to describe a poor skin condition related to a rough and dry skin surface that develops as a result of various damaging effects from the environment or skin inflammation. Recovery from skin roughness requires skin care for a long period, thus it is important to prevent development of such skin changes. PROTECT X2 contains agents used for a protective covering of the skin from frequent hand washing or use of alcohol-based disinfectants. These unique components are also thought to be effective to treat skin roughness of the dorsa of the hands and heels. In the present study, we evaluated the effectiveness of PROTECT X2 to increase skin surface hydration state, as well as enhance the barrier function of the stratum corneum of the dorsa of the hands and heels in elderly individuals. A total of 8 elderly subjects and their caretakers without any skin diseases participated in the study. They applied PROTECT X2 by themselves to the dorsum area of 1 hand and heel 3 to 5 times daily for 1 month, while the opposite sides were left untreated. We measured stratum corneum (SC) hydration and transepidermal water loss (TEWL) before beginning treatment, then 1 week and 1 month after the start of treatment to compare between the treated and untreated skin. SC hydration state after applications of PROTECT X2 was 1.5- to 3.0-fold higher than that of the untreated skin in the dorsa of both hands and heels, indicating that the moisturizing ingredients accompanied by water were replenished in those areas where the cream was applied. Also, TEWL in the dorsum of the hands was 17.0-27.9% lower on the treated side, indicating improvement in SC barrier function. On the basis of these findings, we concluded that PROTECT X2 enhances water-holding in the SC and aids the barrier function of the skin in the dorsum of the hands. In addition, we consider that this formulation is useful for not only protecting the hands from the effects of such agents

Quantification of changes in skin hydration and sebum after tape stripping using infrared spectroscopy

NASA Astrophysics Data System (ADS)

Ezerskaia, A.; Pereira, S. F.; Urbach, H. P.; Varghese, B.

2017-02-01

Skin barrier function relies on well balanced water and lipid system of stratum corneum. Optimal hydration and oiliness levels are indicators of skin health and integrity. We demonstrate an accurate and sensitive depth profiling of stratum corneum sebum and hydration levels using short wave infrared spectroscopy in the spectral range around 1720 nm. We demonstrate that short wave infrared spectroscopic technique combined with tape stripping can provide morequantitative and more reliable skin barrier function information in the low hydration regime, compared to conventional biophysical methods.

Investigation of depilatory mechanism by use of multiphoton fluorescent microscopy

NASA Astrophysics Data System (ADS)

Lin, Chiao-Ying; Lee, Gie-ne; Jee, Shiou-Hwa; Dong, Chen-Yuan; Lin, Sung-Jan

2007-07-01

Transdermal drug delivery provides a non-invasive route of drug administration, and can be a alternative method to oral delivery and injection. The stratum corneum (SC) of skin acts as the main barrier to transdermal drug delivery. Studies suggest that depilatory enhances permeability of drug through the epidermis. However, transdermal delivery pathway and mechanism are not completely understood. Previous studies have found that depilatory changes the keratinocytes of epidermis, and cause the protein in combination with lipid extraction of SC to become disordered. Nevertheless, those studies did not provide images of those processes. The aim of this study is to characterize the penetration enhancing effect of depilatory agent and the associated structural alterations of stratum corneum. Fresh human foreskin is treated by a depilatory agent for 10 minutes and then subjected to the treatment of fluorescent model drugs of hydrophilic rhodamine and hydrophobic rhodamine-RE. The penetration of model drugs is imaged and quantified by multiphoton microscopy. Our results showed that the penetration of both hydrophilic and hydrophobic agents can be enhanced and multifocal detachment of surface corneocytes is revealed. Nile red staining revealed, instead of a regular motar distribution of lipid around the brick of corneocytes, a disorganized and homogenized pattern of lipid distribution. We concluded that depilatory agents enhance drug penetration by disrupting both the cellular integrity of corneocytes and the regular packing of intercellular lipid of stratum corneum.

Human axillary skin condition is improved following incorporation of glycerol into the stratum corneum from an antiperspirant formulation.

PubMed

Evans, Richard L; Turner, Graham A; Bates, Susan; Robinson, Teresa; Arnold, David; Marriott, Robert E; Pudney, Paul D A; Bonnist, Eleanor Y M; Green, Darren

2017-11-01

The study objectives were to demonstrate that glycerol, when topically applied from a roll-on antiperspirant formulation, can be delivered directly to human skin ex vivo and the axillary stratum corneum (SC) in vivo, and to assess whether it improves the quality of the axillary skin barrier. Ex vivo human skin absorption of glycerol was measured following application of a roll-on antiperspirant formulation containing 4% 13 C 3 -glycerol. Skin distribution of 13 C 3 -glycerol over 24 h was assessed using gas chromatography-mass spectrometry. In vivo axillary SC penetration was measured by confocal Raman spectroscopy and multivariate curve-resolution software 1 h after topical application of a roll-on antiperspirant formulation containing 8% deuterated glycerol (d 5 -glycerol). A clinical study was conducted to determine the efficacy of a roll-on antiperspirant formulation containing 4% glycerol in reducing shaving-induced visual irritation and in increasing axillary-skin hydration. Ex vivo skin absorption studies indicated that the formulation delivered 13 C 3 -glycerol into the SC at all timepoints over the 24-h period. In vivo Raman measurements (1 h after application) demonstrated that d 5 -glycerol was detectable to a depth of at least 10 μm in the axillary SC. Application of 4% glycerol from a roll-on antiperspirant formulation to the axilla was associated with significantly less visible irritation and greater skin hydration than observed with the control (glycerol-free) product. These studies demonstrate that glycerol, incorporated in a roll-on antiperspirant formulation, is delivered directly and rapidly to all depths of the axillary SC, and results in improvements in visible irritation and hydration in the axilla.

Documentation of normal stratum corneum scaling in an average population: features of differences among age, ethnicity and body site.

PubMed

Chu, M; Kollias, N

2011-03-01

Scaling skin involves an imbalance between cell proliferation and desquamation, resulting in partially detached corneocytes at the stratum corneum (SC) surface that become visible as they scatter light. The purpose of this study was to document scaling skin with no associated pathology, to estimate the range of normal corneocyte detachment in the average population, and to determine if age, pigmentation and/or body sites of different exposures contribute to differences observed in the SC. Healthy African-American and Caucasian female subjects (n = 151) from a typical central New Jersey population, aged between 14 and 75 years, were evaluated on the dorsal forearm and upper inner arm. Dermatoscopy and adhesive tape were used to evaluate the appearance and adhesion of surface corneocytes. Transepidermal water loss and conductivity were measured to assess water-handling properties of the SC. Measurements were conducted during the winter. Corneocyte detachment observed with dermatoscopy became more prevalent with age and was more severe on the dorsal forearm and in Caucasian subjects. The distribution of the amount of corneocyte removal with adhesive tape increased with age. The range of values was larger in the dorsal forearm than the upper inner arm and was greater in Caucasian subjects than African-American subjects. Minimal changes were observed for water-handling properties. The architecture of the outer SC appears different between ages, body sites of different exposures, and individuals of different pigmentation groups, but minimal differences in water-handling properties are observed. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

Correlation of the penetration enhancement with the influence of an alcohol/tocopheryl polyethylene glycol succinate (TPGS) cosolvent system on the molecular structure of the stratum corneum of nude mouse skin as examined by microscopic FTIR/DSC

NASA Astrophysics Data System (ADS)

Liou, Yi-Bo; Ho, Hsiu-O.; Chen, Shin-Yi; Sheu, Ming-Thau

2009-10-01

Tocopheryl polyethylene glycol succinate (TPGS) is a water-soluble derivative of natural source of vitamin E, which possesses a dual nature of lipophilicity and hydrophilicity, similar to a surface-active agent. The penetration enhancement of estradiol by an ethanol and TPGS cosolvent system (EtOH/TPGS) has been confirmed. In this study, the correlation of the penetration enhancement with the influence of the EtOH/TPGS cosolvent system on biophysical changes of the stratum corneum (SC) as examined by Fourier transformation infrared spectrometry differential scanning calorimetry (FTIR/DSC) was investigated. Thermotropic changes in the asymmetrical and symmetrical C-H stretching of hydrocarbon chains of lipids, and amide I and II bands that characterize the protein structure of the SC treated with different concentrations of the EtOH/TPGS cosolvent were examined in this investigation. Results demonstrated that a strong correlation of the influence on biophysical changes of the SC treated with the EtOH/TPGS cosolvent system with the penetration enhancement of estradiol by the corresponding cosolvent system was not evident. It was concluded that the incorporation of TPGS in the cosolvent system seemed only to have insignificantly modified the structural features of the SC. It was not obvious that the penetrant had encountered these modifications resulting in an improvement in the penetration of estradiol by TPGS.

The long periodicity phase (LPP) controversy part I: The influence of a natural-like ratio of the CER[EOS] analogue [EOS]-br in a CER[NP]/[AP] based stratum corneum modelling system: A neutron diffraction study.

PubMed

Schmitt, Thomas; Lange, Stefan; Sonnenberger, Stefan; Dobner, Bodo; Demé, Bruno; Langner, Andreas; Neubert, Reinhard H H

2018-06-18

This study used neutron diffraction to investigate a ceramide-[NP] C24/[AP] C24 /[EOS]-br C30/cholesterol/lignoceric acid (0.6: 0.3: 0.1: 0.7: 1) based stratum corneum modelling system. By adding specifically deuterated ceramides-[NP]-D 3 , [AP]-D 3 , and [EOS]-br-D 3 , detailed information on the lamellar and the nanostructure of the system was obtained. For the short periodicity phase a natural-like lamellar repeat distance of 5.47 ± 0.02 nm was observed, similar to the [NP]/[AP] base system without the [EOS]-br. Unlike in this system the ceramides here were slightly tilted, hinting towards a slightly less natural arrangement. Due to the deuteration it was possible to observe that the long ceramide chains were overlapping in the lamellar mid-plane. This is considered to be an important feature for the natural stratum corneum. Despite the presence of a ceramide [EOS] analogue - able to form a long phase arrangement - no distinct long periodicity phase was formed, despite a slightly higher than natural ω-acyl ceramide ratio of 10 mol%. The deuterated variant of this ceramide determined that the very long ceramide was integrated into the short periodicity phase, spanning multiple layers instead. The - compared to the base system - unchanged repeat distance highlights the stability of this structure. Furthermore, the localisation of the very long ceramide in the short periodicity phase indicates the possibility of a crosslinking effect and thus a multilayer stabilizing role for the ceramide [EOS]. It can be concluded, that additionally to the mere presence of ceramide-[EOS] more complex conditions have to be met in order to form this long phase. This has to be further investigated in the future. Copyright © 2018 Elsevier B.V. All rights reserved.

Characterization of atopic skin and the effect of a hyperforin-rich cream by laser scanning microscopy.

PubMed

Meinke, Martina C; Richter, Heike; Kleemann, Anke; Lademann, Juergen; Tscherch, Kathrin; Rohn, Sascha; Schempp, Christoph M

2015-05-01

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease that affects both children and adults in an increasing manner. The treatment of AD often reduces subjective skin parameters, such as itching, dryness, and tension, but the inflammation cannot be cured. Laser scanning microscopy was used to investigate the skin surface, epidermal, and dermal characteristics of dry and atopic skin before and after treatment with an ointment rich in hyperforin, which is known for its anti-inflammatory effects. The results were compared to subjective parameters and transepidermal water loss, stratum corneum moisture, and stratum corneum lipids. Using biophysical methods, in particular laser scanning microscopy, it was found that atopic skin has distinct features compared to healthy skin. Treatment with a hyperforin-rich ointment resulted in an improvement of the stratum corneum moisture, skin surface dryness, skin lipids, and the subjective skin parameters, indicating that the barrier is stabilized and improved by the ointment. But in contrast to the improved skin surface, the inflammation in the deeper epidermis/dermis often continues to exist. This could be clearly shown by the reflectance confocal microscopy (RCM) measurements. Therefore, RCM measurements could be used to investigate the progress in treatment of atopic dermatitis.

Characterization of atopic skin and the effect of a hyperforin-rich cream by laser scanning microscopy

NASA Astrophysics Data System (ADS)

Meinke, Martina C.; Richter, Heike; Kleemann, Anke; Lademann, Juergen; Tscherch, Kathrin; Rohn, Sascha; Schempp, Christoph M.

2015-05-01

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease that affects both children and adults in an increasing manner. The treatment of AD often reduces subjective skin parameters, such as itching, dryness, and tension, but the inflammation cannot be cured. Laser scanning microscopy was used to investigate the skin surface, epidermal, and dermal characteristics of dry and atopic skin before and after treatment with an ointment rich in hyperforin, which is known for its anti-inflammatory effects. The results were compared to subjective parameters and transepidermal water loss, stratum corneum moisture, and stratum corneum lipids. Using biophysical methods, in particular laser scanning microscopy, it was found that atopic skin has distinct features compared to healthy skin. Treatment with a hyperforin-rich ointment resulted in an improvement of the stratum corneum moisture, skin surface dryness, skin lipids, and the subjective skin parameters, indicating that the barrier is stabilized and improved by the ointment. But in contrast to the improved skin surface, the inflammation in the deeper epidermis/dermis often continues to exist. This could be clearly shown by the reflectance confocal microscopy (RCM) measurements. Therefore, RCM measurements could be used to investigate the progress in treatment of atopic dermatitis.

Interaction of phloretin and 6-ketocholestanol with DPPC-liposomes as phospholipid model membranes.

PubMed

Auner, Barbara G; O'Neill, Michael A A; Valenta, Claudia; Hadgraft, Jonathan

2005-04-27

Phloretin and 6-ketocholestanol are penetration enhancers for percutaneous delivery of certain topically applied drugs. In the present study some physicochemical experiments have been performed to elucidate the mechanism of action of phloretin and 6-ketocholestanol. The penetration enhancing effect of phloretin and 6-ketocholestanol is believed to be due to their increase of the fluidity of the intercellular lipid bilayers of the stratum corneum. Phospholipid vesicles were chosen as a simple model to represent these bilayers. The effect of phloretin and 6-ketocholestanol on phase transition temperature and enthalpy was studied using differential scanning calorimetry. Beside of that the size of liposomes was monitored when the amount of penetration enhancer in the liposome preparation was changed. Addition of increasing amounts of phloretin and 6-ketocholestanol to the bilayer resulted in lowering of phase transition temperatures and increasing the enthalpy. Additionally the size of the liposomes was increased when penetration enhancer was added. The results suggest that phloretin as well as 6-ketocholestanol would interact with stratum corneum lipids in a similar manner, both reduce the diffusional resistance of the stratum corneum to drugs with balanced hydrophilic-lipophilic characteristics.

An unsupervised machine learning method for delineating stratum corneum in reflectance confocal microscopy stacks of human skin in vivo

NASA Astrophysics Data System (ADS)

Bozkurt, Alican; Kose, Kivanc; Fox, Christi A.; Dy, Jennifer; Brooks, Dana H.; Rajadhyaksha, Milind

2016-02-01

Study of the stratum corneum (SC) in human skin is important for research in barrier structure and function, drug delivery, and water permeability of skin. The optical sectioning and high resolution of reflectance confocal microscopy (RCM) allows visual examination of SC non-invasively. Here, we present an unsupervised segmentation algorithm that can automatically delineate thickness of the SC in RCM images of human skin in-vivo. We mimic clinicians visual process by applying complex wavelet transform over non-overlapping local regions of size 16 x 16 μm called tiles, and analyze the textural changes in between consecutive tiles in axial (depth) direction. We use dual-tree complex wavelet transform to represent textural structures in each tile. This transform is almost shift-invariant, and directionally selective, which makes it highly efficient in texture representation. Using DT-CWT, we decompose each tile into 6 directional sub-bands with orientations in +/-15, 45, and 75 degrees and a low-pass band, which is the decimated version of the input. We apply 3 scales of decomposition by recursively transforming the low-pass bands and obtain 18 bands of different directionality at different scales. We then calculate mean and variance of each band resulting in a feature vector of 36 entries. Feature vectors obtained for each stack of tiles in axial direction are then clustered using spectral clustering in order to detect the textural changes in depth direction. Testing on a set of 15 RCM stacks produced a mean error of 5.45+/-1.32 μm, compared to the "ground truth" segmentation provided by a clinical expert reader.

The Permeability Enhancing Mechanism of DMSO in Ceramide Bilayers Simulated by Molecular Dynamics

PubMed Central

Notman, Rebecca; den Otter, Wouter K.; Noro, Massimo G.; Briels, W. J.; Anwar, Jamshed

2007-01-01

The lipids of the topmost layer of the skin, the stratum corneum, represent the primary barrier to molecules penetrating the skin. One approach to overcoming this barrier for the purpose of delivery of active molecules into or via the skin is to employ chemical permeability enhancers, such as dimethylsulfoxide (DMSO). How these molecules exert their effect at the molecular level is not understood. We have investigated the interaction of DMSO with gel-phase bilayers of ceramide 2, the predominant lipid in the stratum corneum, by means of molecular dynamics simulations. The simulations satisfactorily reproduce the phase behavior and the known structural parameters of ceramide 2 bilayers in water. The effect of DMSO on the gel-phase bilayers was investigated at various concentrations over the range 0.0−0.6 mol fraction DMSO. The DMSO molecules accumulate in the headgroup region and weaken the lateral forces between the ceramides. At high concentrations of DMSO (≥0.4 mol fraction), the ceramide bilayers undergo a phase transition from the gel phase to the liquid crystalline phase. The liquid-crystalline phase of ceramides is expected to be markedly more permeable to solutes than the gel phase. The results are consistent with the experimental evidence that high concentrations of DMSO fluidize the stratum corneum lipids and enhance permeability. PMID:17513383

Large-scale human skin lipidomics by quantitative, high-throughput shotgun mass spectrometry.

PubMed

Sadowski, Tomasz; Klose, Christian; Gerl, Mathias J; Wójcik-Maciejewicz, Anna; Herzog, Ronny; Simons, Kai; Reich, Adam; Surma, Michal A

2017-03-07

The lipid composition of human skin is essential for its function; however the simultaneous quantification of a wide range of stratum corneum (SC) and sebaceous lipids is not trivial. We developed and validated a quantitative high-throughput shotgun mass spectrometry-based platform for lipid analysis of tape-stripped SC skin samples. It features coverage of 16 lipid classes; total quantification to the level of individual lipid molecules; high reproducibility and high-throughput capabilities. With this method we conducted a large lipidomic survey of 268 human SC samples, where we investigated the relationship between sampling depth and lipid composition, lipidome variability in samples from 14 different sampling sites on the human body and finally, we assessed the impact of age and sex on lipidome variability in 104 healthy subjects. We found sebaceous lipids to constitute an abundant component of the SC lipidome as they diffuse into the topmost SC layers forming a gradient. Lipidomic variability with respect to sampling depth, site and subject is considerable, and mainly accredited to sebaceous lipids, while stratum corneum lipids vary less. This stresses the importance of sampling design and the role of sebaceous lipids in skin studies.

Partial ablation of stratum corneum by UV (193-nm) or IR (2.94-μm) pulsed lasers to enhance transdermal drug delivery rate

NASA Astrophysics Data System (ADS)

Fujiwara, Ai; Hinokitani, Toshihiro; Goto, Kenichi; Arai, Tsunenori

2004-07-01

To develop the noninvasive transdermal drug delivery system, pulsed lasers (argon-fluoride excimer laser (ArF laser) and erbium:yittrium aluminum garnet laser (Er:YAG laser)) were used to partially ablate the stratum corneum (SC), the upper layer of the skin. Because of the barrier function of the SC to drug permeation, the number of drugs especially macromolecules used in transdermal drug delivery system without skin irritation has been limited. Ultrastructural changes on the SC surface of ablated Yucatan micropig skin in vitro were observed with Environmental Scanning Electron Microscope. The result indicated that the structural changes varied according to each laser sources and irradiation conditions (laser fluences and numbers of pulses). Many granular structures of about 2 μm in diameter were observed in the ablated sites on ArF laser with lower fluence exposure (30 mJ/cm2, 200 pulses), and plane structures in the sites with higher fluence exposure (80 mJ/cm2, 80 pulses). In contrast, the ablation of Er:YAG laser created some pores of about 20 μm across on the surface of the SC. Under the irradiation condition of partial ablation, the skin permeability of macromolecule compound was enhanced. This partial SC ablation by pulsed laser could be possible candidate of the noninvasive transdermal drug delivery system with good physiological conditions of skin.

Isolated human and animal stratum corneum as a partial model for the 15 steps of percutaneous absorption: emphasizing decontamination, part II.

PubMed

Hui, Xiaoying; Lamel, Sonia; Qiao, Peter; Maibach, Howard I

2013-03-01

Cutaneously directed chemical warfare agents can elicit significant morbidity and mortality. The optimization of prophylactic and therapeutic interventions counteracting these agents is crucial, and the development of decontamination protocols and methodology of post dermal exposure risk assessments would be additionally applicable to common industrial and consumer dermatotoxicants. Percutaneous (PC) penetration is often considered a simple one-step diffusion process but presently consists of at least 15 steps. The systemic exposure to an agent depends on multiple factors and the second part of this review covers absorption and excretion kinetics, wash and rub effects, skin substantivity and transfer, among others. Importantly, the partitioning behavior and diffusion through the stratum corneum (SC) of a wide physicochemical array of compounds shows that many compounds have approximately the same diffusion coefficient which determines their percutaneous absorption in vivo. After accounting for anatomical variation of the SC, the penetration flux value of a substance depends mainly on its SC/vehicle partition coefficient. Additionally, the SC acts as a 'reservoir' for topically applied molecules, and tape stripping methodology can quantify the remaining chemical in the SC which can predict the total molecular penetration in vivo. The determination of ideal decontamination protocols is of utmost importance to reduce morbidity and mortality. However, even expeditious standard washing procedures post dermal chemical exposure often fails to remove chemicals. The second part of this overview continues to review percutaneous penetration extending insights into the complexities of penetration, decontamination and potential newer assays that may be of practical importance. Copyright © 2012 John Wiley & Sons, Ltd.

Changes in hydration of the stratum corneum are the most suitable indicator to evaluate the irritation of surfactants on the skin.

PubMed

Fujimura, T; Shimotoyodome, Y; Nishijima, T; Sugata, K; Taguchi, H; Moriwaki, S

2017-02-01

Irritancy levels of surfactants on human skin have not been clarified completely. The relationships between skin damage and changes of skin properties caused by various surfactants were investigated using non-invasive measurements. Aqueous solutions of seven kinds of anionic, non-ionic, and amphoteric surfactants were exposed to the inside of forearm skin of 20 human subjects in two separate studies using the cup method. Hydration of the stratum corneum (SC), transepidermal water loss (TEWL), pH, skin surface roughness, and contents of the SC were measured before and after one exposure and after five and nine consecutive exposures to various surfactants. The discontinuation ratio of subjects for testing in each surfactant was determined by skin irritation symptoms and was defined as the degree of skin damage. Significant changes were observed only in hydration, TEWL, and natural moisturizing factors (NMF) content in the SC following surfactant exposure. A significant correlation was observed between the discontinuation ratio of each surfactant and the changes of hydration, TEWL, and NMF. Especially, the change of SC hydration showed an excellent correlation with the discontinuation ratio both for single (r = 0.942, P < 0.001) and for chronic exposures (r = 0.934, P < 0.001). Our results indicate that the change of hydration of the SC is equivalent to the skin damage caused by surfactants, and therefore is the most suitable indicator to evaluate the irritation of surfactants on the skin. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparison of structure and organization of cutaneous lipids in a reconstructed skin model and human skin: spectroscopic imaging and chromatographic profiling.

PubMed

Tfayli, Ali; Bonnier, Franck; Farhane, Zeineb; Libong, Danielle; Byrne, Hugh J; Baillet-Guffroy, Arlette

2014-06-01

The use of animals for scientific research is increasingly restricted by legislation, increasing the demand for human skin models. These constructs present comparable bulk lipid content to human skin. However, their permeability is significantly higher, limiting their applicability as models of barrier function, although the molecular origins of this reduced barrier function remain unclear. This study analyses the stratum corneum (SC) of one such commercially available reconstructed skin model (RSM) compared with human SC by spectroscopic imaging and chromatographic profiling. Total lipid composition was compared by chromatographic analysis (HPLC). Raman spectroscopy was used to evaluate the conformational order, lateral packing and distribution of lipids in the surface and skin/RSM sections. Although HPLC indicates that all SC lipid classes are present, significant differences are observed in ceramide profiles. Raman imaging demonstrated that the RSM lipids are distributed in a non-continuous matrix, providing a better understanding of the limited barrier function. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dexpanthenol enhances skin barrier repair and reduces inflammation after sodium lauryl sulphate-induced irritation.

PubMed

Proksch, E; Nissen, H P

2002-12-01

Dexpanthenol-containing creams have been widely used for treatment of lesions (superficial wounds) of the skin and mucous membranes. Dexpanthenol is converted in tissues to pantothenic acid, a component of coenzyme A. Coenzyme A catalyses early steps in the synthesis of fatty acids and sphingolipids which are of crucial importance for stratum corneum lipid bilayers and cell membrane integrity. In the present study, the effects were examined of a dexpanthenol-containing cream on skin barrier repair, stratum corneum hydration, skin roughness, and inflammation after sodium lauryl sulphate (SLS)-induced irritation. Irritation was induced by application of SLS in patch test chambers. The dexpanthenol-contaming cream or the vehicle were applied twice daily and barrier repair, hydration, roughness, and inflammation of the skin were determined by using biophysical methods. Significantly accelerated skin barrier repair was found in treatments with the dexpanthenol-containing cream (verum) compared with vehicle-treated (placebo) or untreated skin. Both verum and placebo showed an increase in stratum corneum hydration, but significantly more so with the dexpanthenol-containing cream. Both creams reduced skin roughness, but again the verum was superior. The dexpanthenol-containing cream significantly reduced skin redness as a sign of inflammation in contrast to the vehicle, which produced no effect. Treatment with a dexpanthenol-containing cream showed significantly enhanced skin barrier repair and stratum corneum hydration, while reducing skin roughness and inflammation.

Characterization of silver particles in the stratum corneum of healthy subjects and atopic dermatitis patients dermally exposed to a silver-containing garment

PubMed Central

Bianco, Carlotta; Visser, Maaike J.; Pluut, Olivier A.; Svetličić, Vesna; Pletikapić, Galja; Jakasa, Ivone; Riethmuller, Christoph; Adami, Gianpiero; Filon, Francesca Larese; Schwegler-Berry, Diane; Stefaniak, Aleksandr B.; Kezic, Sanja

2018-01-01

Silver is increasingly being used in garments to exploit its antibacterial properties. Information on the presence of silver nanoparticles (AgNPs) in garments and their in vivo penetration across healthy and impaired skin from use is limited. We investigated the presence of AgNPs in a silver containing garment and in the stratum corneum (SC) of healthy subjects (CTRLs) and individuals with atopic dermatitis (AD). Seven CTRLs and seven AD patients wore a silver sleeve (13% Ag w/w) 8 h/day for five days on a forearm and a placebo sleeve on the other forearm. After five days, the layers of the SC were collected by adhesive tapes. The silver particles in the garment and SC were characterized by scanning electron microscopy with energy dispersive X-ray analysis (SEM-EDX) and atomic force microscopy (AFM). AFM and SEM revealed the presence of sub-micrometre particles having a broad range of sizes (30–500 nm) on the surface of the garment that were identified as silver. On the SC tapes collected from different depths, aggregates with a wide range of sizes (150 nm−2 μm) and morphologies were found. Most aggregates contained primarily silver, although some also contained chlorine and sulfur. There was no clear difference in the number or size of the aggregates observed in SC between healthy and AD subjects. After use, AgNPs and their aggregates were present in the SC at different depths of both healthy subjects and AD patients. Their micrometre size suggests that aggregation likely occurred in the SC. PMID:27647219

Microfabrication of individual 200 microm diameter transdermal microconduits using high voltage pulsing in salicylic acid and benzoic acid.

PubMed

Ilic, L; Gowrishankar, T R; Vaughan, T E; Herndon, T O; Weaver, J C

2001-01-01

We describe an extension of semiconductor fabrication methods that creates individual approximately 200 microm diameter aqueous pathways through human stratum corneum at predetermined sites. Our hypothesis is that spatially localized electroporation of the multilamellar lipid bilayer membranes provides rapid delivery of salicylic acid to the keratin within corneocytes, leading to localized keratin disruption and then to a microconduit. A microconduit penetrating the isolated stratum corneum supports a volumetric flow of order 0.01 ml per s with a pressure difference of only 0.01 atm (about 10(2) Pa). This study provides a method for rapidly microengineering a pathway in the skin to interface future devices for transdermal drug delivery and sampling of biologically relevant fluids.

Atopic March from Atopic Dermatitis to Asthma-Like Lesions in NC/Nga Mice Is Accelerated or Aggravated by Neutralization of Stratum Corneum but Partially Inhibited by Acidification.

PubMed

Lee, Hae-Jin; Lee, Noo Ri; Jung, Minyoung; Kim, Dong Hye; Choi, Eung Ho

2015-12-01

Prolonged and/or repeated damage to the skin barrier followed by atopic dermatitis (AD) is an initial step in atopic march that ultimately progresses to respiratory allergy. Maintaining normal stratum corneum (SC) acidity has been suggested as a therapeutic or preventive strategy for barrier impairment caused by skin inflammation. We determined whether a representative AD murine model, NC/Nga mice, develops airway inflammation after repeated epicutaneous application followed by inhalation of house dust mite (HDM), implying atopic march, and whether prolongation of non-proper SC acidity accelerates respiratory allergy. HDM was applied to the skin of NC/Nga mice, accompanied by the application of neutral cream (pH 7.4) or acidic cream (pH 2.8) for 6 weeks. Intranasal inhalation of HDM was administered daily during the last 3 days. Repeated epicutaneous applications followed by inhalation of HDM in NC/Nga mice induced an atopic march-like progression from AD lesions to respiratory allergy. Concurrent neutral cream treatment accelerated or aggravated the allergic inflammation in the skin and respiratory system, whereas an acidic cream partially alleviated these symptoms. Collectively, we developed an atopic march in NC/Nga mice by HDM application, and found that prevention of a neutral environment in the SC may be an interventional method to inhibit the march.

Effect of various enhancers on transdermal penetration of indomethacin and urea, and relationship between penetration parameters and enhancement factors.

PubMed

Ogiso, T; Iwaki, M; Paku, T

1995-04-01

The enhancing capacity of various chemicals, which are widely recognized as enhancers, for the transdermal penetration into full-thickness rat skin of a model lipophilic drug [indomethacin (IND)] and a hydrophilic permeant (urea) was estimated by an in vitro technique. In addition, the fluidity of the stratum corneum lipids, the partitioning of IND into skin, the lipid (ceramides) extraction from the stratum corneum by enhancers, and the IND solubility in enhancer vehicle were measured and related to the enhancing capacity. In vitro permeation experiments with hairless rat skin unequivocally revealed that the enhancers varied in abilities to enhance the fluxes of both agents. Laurocapram, isopropylmyristate (IPM), sodium oleate, and cineol increased fluxes of both agents to a great extent, but N-methyl-2-pyrrolidone (NMP), N,N-diethyl-m-tolamide (DEET), and oleyl oleate were less effective acclerants. Many enhancers increased the fluidity of the lipids [with a threshold of approximately 0.6-0.8 ns at 37 degrees C in the rotational correlation time (tau c)], the skin partitioning of IND, the extraction of ceramides from the cornified cells, and the thermodynamic activity of IND in vehicle (calculated from the solubility) to varying extents. A good correlation was observed between the increase in the fluidity of stratum corneum lipids and the partitioning of IND into skin, between the increase in the fluidity and the flux or the decrease in lag time for IND, between the removal of ceramides and the skin partitioning of IND, and between the removal of ceramides and the flux of urea (p < 0.05 in all cases).(ABSTRACT TRUNCATED AT 250 WORDS)

ATR-IR study of skin components: Lipids, proteins and water. Part I: Temperature effect

NASA Astrophysics Data System (ADS)

Olsztyńska-Janus, S.; Pietruszka, A.; Kiełbowicz, Z.; Czarnecki, M. A.

2018-01-01

In this work we report the studies of the effect of temperature on skin components, such as lipids, proteins and water. Modifications of lipids structure induced by increasing temperature (from 20 to 90 °C) have been studied using ATR-IR (Attenuated Total Reflectance Infrared) spectroscopy, which is a powerful tool for characterization of the molecular structure and properties of tissues, such as skin. Due to the small depth of penetration (0.6-5.6 μm), ATR-IR spectroscopy probes only the outermost layer of the skin, i.e. the stratum corneum (SC). The assignment of main spectral features of skin components allows for the determination of phase transitions from the temperature dependencies of band intensities [e.g. νas(CH2) and νs(CH2)]. The phase transitions were determined by using two methods: the first one was based on the first derivative of the Boltzmann function and the second one employed tangent lines of sigmoidal, aforementioned dependencies. The phase transitions in lipids were correlated with modifications of the structure of water and proteins.

Rapid, simultaneous and nanomolar determination of pyroglutamic acid and cis-/trans-urocanic acid in human stratum corneum by hydrophilic interaction liquid chromatography (HILIC)-electrospray ionization tandem mass spectrometry.

PubMed

Joo, Kyung-Mi; Han, Ji Yeon; Son, Eui Dong; Nam, Gae-Won; Chung, Han Young; Jeong, Hye-Jin; Cho, Jun-Cheol; Lim, Kyung-Min

2012-05-15

A rapid, sensitive and specific hydrophilic interaction liquid chromatography coupled to tandem mass spectrometric (HILIC-MS/MS) method for the simultaneous determination of pyroglutamic acid, cis- and trans-urocanic acid in human skin stratum corneum (SC) were developed and validated. This method was carried out without derivatization or addition of ion-pair additives in mobile phase. The analytes were extracted by PBS buffer solution and analyzed using an electrospray positive ionization mass spectrometry in the multiple reaction monitoring (MRM) mode. Chromatographic separation was performed on an AQUITY UPLC amide column using gradient elution with the mobile phase of water and acetonitrile. The standard curves were linear over the concentration range of 1.0-250 ng/mL with a correlation coefficient higher than 0.999 with an LLOQ of 0.5 ng/mL. The lower limits of detection (LLOD) of these analytes were lower than 0.2 ng/mL. The intra- and inter-day precisions were measured to be below 7.7% and accuracies were within the range of 94.3-102.6%. The validated method was successfully applied to determine the level of pyroglutamic acid and cis-/trans-urocanic acid in the SC samples from forearm and forehead region of 19 human volunteers. Copyright © 2012 Elsevier B.V. All rights reserved.

Transdermal drug delivery: from micro to nano

NASA Astrophysics Data System (ADS)

Pegoraro, Carla; MacNeil, Sheila; Battaglia, Giuseppe

2012-03-01

Delivery across skin offers many advantages compared to oral or intravenous routes of drug administration. Skin however is highly impermeable to most molecules on the basis of size, hydrophilicity, lipophilicity and charge. For this reason it is often necessary to temporarily alter the barrier properties of skin for effective administration. This can be done by applying chemical enhancers, which alter the lipid structure of the top layer of skin (the stratum corneum, SC), by applying external forces such as electric currents and ultrasounds, by bypassing the stratum corneum via minimally invasive microneedles or by using nano-delivery vehicles that can cross and deliver their payload to the deeper layers of skin. Here we present a critical summary of the latest technologies used to increase transdermal delivery.

From contact angle titration to chemical force microscopy: a new route to assess the pH-dependent character of the stratum corneum.

PubMed

Wagner, Matthieu; Mavon, Alain; Haidara, Hamidou; Vallat, Marie-France; Duplan, Hélène; Roucoules, Vincent

2012-02-01

Despite of its complex multicomponent organization and its compact architecture, the Stratum corneum (SC) is not completely impermeable to substances directly applied on the skin surface. A huge number of works have been dedicated to the understanding of the mechanisms involved in substance permeation by exploring deeper layers than the SC itself. Surprisingly, there is a poor interest in studies relating to interactions which may occur in the near-surface region (i.e. approximately 1 nm depth) of the SC. In this work, equilibrium proton-transfer reactions have been used as probes to define in a fundamental point of view the nature of the SC interactions with its environment. Such titration curves are investigated on 'in vitro' SC (isolated SC from abdominal skin tissue) and on 'in vivo' volar forearm (a sebum poor area). The results are discussed in term of work of adhesion and surface pKa values. Because SC can 'reconstruct' under heating, influence of the temperature on titration curves is investigated and the role of the different components is discussed. Different sigmoidal transitions were observed. Two common pKa values (pKa(1) = 4 and pKa(2) = 11.5) were clearly identified in both cases and associated to an acid-base character. By playing with the temperature of 'in vitro' SC, the 'accessibility' of polar functions was increased, thus refining the results by revealing an amphoteric character with an acid-to-base transition at pH 3.5 and two acid transitions at pH = 6.5 and pH = 11.5. Adhesion forces between an Atomic Force Microscopy (AFM) tip and a single isolated corneocyte through buffered liquid media were also investigated to better understand the role of the individual corneocytes. © 2011 The Authors. ICS © 2011 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Nanostructured lipid carriers to enhance transdermal delivery and efficacy of diclofenac.

PubMed

Nguyen, Chien Ngoc; Nguyen, Thi Thuy Trang; Nguyen, Hanh Thuy; Tran, Tuan Hiep

2017-10-01

Lipid carrier-mediated transdermal drug delivery offers several advantages because it is non-irritating and non-toxic, provides effective control of drug release, and forms an adhesive film that hydrates the outer skin layers. However, to penetrate the deeper skin layers, these formulations need to overcome several barriers in the stratum corneum. This study evaluates factors influencing particle size and drug-loading capacity, which play a key role in drug permeation and efficacy. Diclofenac sodium was chosen as the model drug. The fabrication of diclofenac sodium-loaded lipid nanoparticles was optimized by modulating several parameters, including the lipids and surfactants employed, the drug/lipid ratio, and the pH of the aqueous phase. The physical properties and loading efficiencies of the nanoparticles were characterized. The optimized formulation was then dispersed into a polymer solution to form a gel, which demonstrated a sustained ex vivo permeation of diclofenac sodium over 24 h through excised rat skin and a higher drug penetrating capacity than that of a commercially available gel. In vivo anti-inflammatory activity was assessed in a rat carrageenan-induced paw edema model; the anti-edema effects of the prepared gel and commercially available gel over 24 h were comparable. The present findings indicate the effects of particle size and drug loading on the ability of nanostructured lipid carrier preparations to provide transdermal drug delivery.

Development and evaluation of resveratrol, Vitamin E, and epigallocatechin gallate loaded lipid nanoparticles for skin care applications.

PubMed

Chen, Jin; Wei, Ning; Lopez-Garcia, Maria; Ambrose, Dianna; Lee, Jason; Annelin, Colin; Peterson, Teresa

2017-08-01

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been studied as potential carriers for both dermal and transdermal drug delivery. SLN contain lipid droplets that are fully crystallized and have a highly-ordered crystalline structure. NLC are modified SLN in which the lipid phase contains both solid and liquid lipids at room temperature. SLN and NLC are thought to combine the advantages of polymeric particles, liposomes and emulsions. Therefore they provide high encapsulation percentages, better protection for incorporated actives and allow for control of desired release profile. In this work, Resveratrol, Vitamin E (VE), and Epigallocatechin Gallate (EGCG) all potent antioxidants known to provide protection to the skin, were formulated into lipid nanoparticles. Several different formulations were successfully developed and demonstrated high uniformity and stability. Both resveratrol and VE lipid nanoparticles provided effective protection of actives against UV induced degradation. However, lipid nanoparticles did not show protection from UV degradation for EGCG in this work. An active release study exhibited a sustained release of resveratrol over 70% after 24h. Skin penetration studies showed that lipid nanoparticles directionally improved the penetration of resveratrol through the stratum corneum. Our findings suggest that lipid nanoparticles are promising viable carriers for the delivery of resveratrol and VE to provide longlasting antioxidant benefits to the skin. Copyright © 2017 Elsevier B.V. All rights reserved.

Solid lipid nanoparticles bearing oxybenzone: in-vitro and in-vivo evaluation.

PubMed

Gulbake, Arvind; Jain, Aviral; Khare, Piush; Jain, Sanjay K

2010-05-01

In the present project, Solid Lipid Nanoparticles (SLNs) bearing oxybenzone were prepared by ethanol injection method to improve its effectiveness as sunscreen. SLNs were characterized for particle size,polydispersity index, zeta potential and surface morphology. The optimized SLNs bearing oxybenzone were incorporated into water-removable cream base and compared with SLNs unloaded water-removable cream base for in vitro and in vivo parameters. Cream base formulation containing SLNs (Csd) with 5% oxybenzone showed slow drug release and better sun protecting factor (more than 25) compared to cream base containing 5% oxybenzone. Confocal Laser Scanning Microscopy was used to visualize the distribution of developed formulations in skin. CLSM indicated prolonged retention of SLNs in the stratum corneum as compared to plain cream base. These studies revealed that the cream base bearing SLNs exhibited good skin retention as well as enhanced sun protection effect compared to cream base.

Genetic Algorithm for Opto-thermal Skin Hydration Depth Profiling Measurements

NASA Astrophysics Data System (ADS)

Cui, Y.; Xiao, Perry; Imhof, R. E.

2013-09-01

Stratum corneum is the outermost skin layer, and the water content in stratum corneum plays a key role in skin cosmetic properties as well as skin barrier functions. However, to measure the water content, especially the water concentration depth profile, within stratum corneum is very difficult. Opto-thermal emission radiometry, or OTTER, is a promising technique that can be used for such measurements. In this paper, a study on stratum corneum hydration depth profiling by using a genetic algorithm (GA) is presented. The pros and cons of a GA compared against other inverse algorithms such as neural networks, maximum entropy, conjugate gradient, and singular value decomposition will be discussed first. Then, it will be shown how to use existing knowledge to optimize a GA for analyzing the opto-thermal signals. Finally, these latest GA results on hydration depth profiling of stratum corneum under different conditions, as well as on the penetration profiles of externally applied solvents, will be shown.

The rational design of biomimetic skin barrier lipid formulations using biophysical methods.

PubMed

Bulsara, P A; Varlashkin, P; Dickens, J; Moore, D J; Rawlings, A V; Clarke, M J

2017-04-01

The focus of this communication was to study phospholipid-structured emulsions whose phase behaviour is modified with monoalkyl fatty amphiphiles. Ideally, these systems would mimic key physical and structural attributes observed in human stratum corneum (SC) so that they better alleviate xerotic skin conditions. Phosphatidylcholine-structured emulsions were prepared, and their phase behaviour modified with monoalkyl fatty amphiphiles. The effect of molecular volume, acyl chain length and head-group interactions was studied using a combination of physical methods. Water vapour transmission rate (WVTR) was used as a primary test to assess occlusive character. Changes in the vibrational modes observed in Fourier transform infrared (FTIR) spectroscopy and bilayer spacing measured by X-ray diffraction (XRD) were then applied to elucidate the lateral and lamellar microstructural characteristics in the systems. Water vapour transmission rate demonstrated that as the phosphatidylcholine acyl chain length increased from C14, to C18, to C22, there was a corresponding increase in occlusive character. The addition of monoalkyl fatty amphiphiles such as behenic acid, behenyl alcohol or cetostearyl alcohol to a base formulation incorporating dipalmitoyl and distearoylphosphatidylcholine (C18) was seen to further increase barrier characteristics of the emulsions. FTIR methods used to probe lipid-chain conformational ordering demonstrated that as phosphatidylcholine acyl chain lengths increased, there was a corresponding improvement in acyl chain ordering, with an increase in thermal transition temperatures. The addition of a monoalkyl fatty amphiphile resulted in conformational order and thermal transition temperature improvements trending towards those observed in stratum corneum. FTIR also demonstrated that systems containing behenic acid or behenyl alcohol exhibited features associated with orthorhombic character. X-ray diffraction data showed that addition of monoalkyl fatty

Novel phytoceramides containing fatty acids of diverse chain lengths are better than a single C18-ceramide N-stearoyl phytosphingosine to improve the physiological properties of human stratum corneum.

PubMed

Oh, Myoung Jin; Cho, Young Hoon; Cha, So Yoon; Lee, Eun Ok; Kim, Jin Wook; Kim, Sun Ki; Park, Chang Seo

2017-01-01

Ceramides in the human stratum corneum (SC) are a mixture of diverse N -acylated fatty acids (FAs) with different chain lengths. C24 is the major class of FAs of ceramides. However, there are also other classes of ceramides with diverse chain lengths of FAs, and these lengths generally range from C16 to C26. This study aimed to prepare several types of phytoceramide containing diverse chain lengths of N -acylated FAs and compare them with C18-ceramide N -stearoyl phytosphingosine (NP) in terms of their effects on the physiological properties of the SC. We chose natural oils, such as horse fat oil, shea butter, sunflower oil, and a mixture of macadamia nut, shea butter, moringa, and meadowfoam seed oil, as sources of FAs and phytosphingosine as a sphingoid backbone to synthesize diverse phytoceramides. Each phytoceramide exhibited a distinctive formation of the lamellar structure, and their FA profiles were similar to those of their respective natural oil. The skin barrier properties, as analyzed in human skin, clearly demonstrated that all the phytoceramides improved the recovery rate of the damaged SC and enhanced hydration better than C18-ceramide NP did. In conclusion, natural oil-derived phytoceramides could represent a novel class of ceramides for cosmetic applications in the development of an ideal skin barrier moisturizer.

Novel phytoceramides containing fatty acids of diverse chain lengths are better than a single C18-ceramide N-stearoyl phytosphingosine to improve the physiological properties of human stratum corneum

PubMed Central

Oh, Myoung Jin; Cho, Young Hoon; Cha, So Yoon; Lee, Eun Ok; Kim, Jin Wook; Kim, Sun Ki; Park, Chang Seo

2017-01-01

Ceramides in the human stratum corneum (SC) are a mixture of diverse N-acylated fatty acids (FAs) with different chain lengths. C24 is the major class of FAs of ceramides. However, there are also other classes of ceramides with diverse chain lengths of FAs, and these lengths generally range from C16 to C26. This study aimed to prepare several types of phytoceramide containing diverse chain lengths of N-acylated FAs and compare them with C18-ceramide N-stearoyl phytosphingosine (NP) in terms of their effects on the physiological properties of the SC. We chose natural oils, such as horse fat oil, shea butter, sunflower oil, and a mixture of macadamia nut, shea butter, moringa, and meadowfoam seed oil, as sources of FAs and phytosphingosine as a sphingoid backbone to synthesize diverse phytoceramides. Each phytoceramide exhibited a distinctive formation of the lamellar structure, and their FA profiles were similar to those of their respective natural oil. The skin barrier properties, as analyzed in human skin, clearly demonstrated that all the phytoceramides improved the recovery rate of the damaged SC and enhanced hydration better than C18-ceramide NP did. In conclusion, natural oil-derived phytoceramides could represent a novel class of ceramides for cosmetic applications in the development of an ideal skin barrier moisturizer. PMID:28979153

Mechanism and determinants of nanoparticle penetration through human skin

NASA Astrophysics Data System (ADS)

Labouta, Hagar I.; El-Khordagui, Labiba K.; Kraus, Tobias; Schneider, Marc

2011-12-01

The ability of nanoparticles to penetrate the stratum corneum was the focus of several studies. Yet, there are controversial issues available for particle penetration due to different experimental setups. Meanwhile, there is little known about the mechanism and determinants of their penetration. In this paper the penetration of four model gold nanoparticles of diameter 6 and 15 nm, differing in surface polarity and the nature of the vehicle, through human skin was studied using multiphoton microscopy. This is in an attempt to profoundly investigate the parameters governing particle penetration through human skin. Our results imply that nanoparticles at this size range permeate the stratum corneum in a similar manner to drug molecules, mainly through the intercellular pathways. However, due to their particulate nature, permeation is also dependent on the complex microstructure of the stratum corneum with its tortuous aqueous and lipidic channels, as shown from our experiments performed using skin of different grades of barrier integrity. The vehicle (toluene-versus-water) had a minimal effect on skin penetration of gold nanoparticles. Other considerations in setting up a penetration experiment for nanoparticles were also studied. The results obtained are important for designing a new transdermal carrier and for a basic understanding of skin-nanoparticle interaction.

Minoxidil Skin Delivery from Nanoemulsion Formulations Containing Eucalyptol or Oleic Acid: Enhanced Diffusivity and Follicular Targeting

PubMed Central

Abd, Eman; Benson, Heather A. E.; Roberts, Michael S.; Grice, Jeffrey E.

2018-01-01

In this work, we examined enhanced skin delivery of minoxidil applied in nanoemulsions incorporating skin penetration enhancers. Aliquots of fully characterized oil-in-water nanoemulsions (1 mL), containing minoxidil (2%) and the skin penetration enhancer oleic acid or eucalyptol as oil phases, were applied to full-thickness excised human skin in Franz diffusion cells, while aqueous solutions (1 mL) containing minoxidil were used as controls. Minoxidil in the stratum corneum (SC), hair follicles, deeper skin layers, and flux through the skin over 24 h was determined, as well as minoxidil solubility in the formulations and in the SC. The nanoemulsions significantly enhanced the permeation of minoxidil through skin compared with control solutions. The eucalyptol formulations (NE) promoted minoxidil retention in the SC and deeper skin layers more than did the oleic acid formulations, while the oleic acid formulations (NO) gave the greatest hair follicle penetration. Minoxidil maximum flux enhancement was associated with increases in both minoxidil SC solubility and skin diffusivity in both nanoemulsion systems. The mechanism of enhancement appeared to be driven largely by increased diffusivity, rather than increased partitioning into the stratum corneum, supporting the concept of enhanced fluidity and disruption of stratum corneum lipids. PMID:29370122

Skin permeation and antioxidant efficacy of topically applied resveratrol.

PubMed

Alonso, Cristina; Martí, M; Barba, C; Carrer, V; Rubio, L; Coderch, L

2017-08-01

The permeation of resveratrol was assessed by in vitro and in vivo experiments 24 h after topical administration. The in vitro profile of resveratrol was assessed by Raman spectroscopy. Human skin permeation was analysed in vivo by the tape stripping method with the progressive removal of the stratum corneum layers using adhesive tape strips. Moreover, the free radical scavenging activity of resveratrol after its topical application was determined using the DPPH assay. The Raman spectra indicated that the topically applied resveratrol penetrates deep into the skin. The results showed high amounts of resveratrol in the different stratum corneum layers close to the surface and a constant lower amount in the upper layers of the viable epidermis. The concentration of resveratrol present in the outermost stratum corneum layers was obtained by tape stripping after in vivo application. The results demonstrated that resveratrol mainly remained in the human stratum corneum layers. After topical application, resveratrol maintained its antiradical activity. The antioxidant efficacy of the compound was higher in the inner layers of the stratum corneum. As these results have demonstrated, topically applied resveratrol reinforces the antioxidant system of the stratum corneum and provides an efficient means of increasing the tissue levels of antioxidants in the human epidermis.

Applications and limitations of lipid nanoparticles in dermal and transdermal drug delivery via the follicular route.

PubMed

Lauterbach, Andreas; Müller-Goymann, Christel C

2015-11-01

Lipid nanoparticles (LN) such as solid lipid nanoparticles (SLN) and nanolipid carriers (NLC) feature several claimed benefits for topical drug therapy including biocompatible ingredients, drug release modification, adhesion to the skin, and film formation with subsequent hydration of the superficial skin layers. However, penetration and permeation into and across deeper skin layers are restricted due to the barrier function of the stratum corneum (SC). As different kinds of nanoparticles provide the potential for penetration into hair follicles (HF) LN are applicable drug delivery systems (DDS) for this route in order to enhance the dermal and transdermal bioavailability of active pharmaceutical ingredients (API). Therefore, this review addresses the HF as application site, published formulations of LN which showed follicular penetration (FP), and characterization methods in order to identify and quantify the accumulation of API delivered by the LN in the HF. Since LN are based on lipids that appear in human sebum which is the predominant medium in HF an increased localization of the colloidal carriers as well as a promoted drug release may be assumed. Therefore, sebum-like lipid material and a size of less or equal 640 nm are appropriate specifications for FP of particulate formulations. Copyright © 2015 Elsevier B.V. All rights reserved.

Lipid nanoparticles (SLN & NLC) for delivery of vitamin E: a comprehensive review.

PubMed

Saez, V; Souza, I D L; Mansur, C R E

2018-04-01

The antioxidative and photoprotective properties of vitamin E have caused it to be included as an active agent in various pharmaceutical and cosmetic products. However, its lipophilicity, chemical instability and poor skin penetration have limited the effectiveness of these formulations. For that reason, many attempts to include it in different drug delivery systems have been made. In recent decades, lipid nanoparticles have received special attention due to their advantages of compatibility with the skin, ability to enhance penetration of drugs in the stratum corneum, protection of the encapsulated substance against degradation induced by the external medium and control of drug release. This work reviews the current status of the encapsulation of vitamin E in lipid nanoparticles. We describe the most important methods for obtaining and characterizing lipid nanoparticles containing vitamin E (LNP-VE), various techniques for the evaluation of vitamin E's properties after encapsulation, the main in vitro and in vivo studies of the potential effectiveness or toxicity of LNP-VE, the formulations and stability studies of this delivery system, the commercial products based on LNP-VE and the regulatory aspects related to lipid nanoparticles. Finally, we discuss the most relevant advantages of encapsulating vitamin E in such particles and critical aspects that still demand attention to enhance the potential of solid lipid nanoparticles to deliver vitamin E. © 2018 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Phytosphingosine, sphingosine and dihydrosphingosine ceramides in model skin lipid membranes: permeability and biophysics.

PubMed

Školová, Barbora; Kováčik, Andrej; Tesař, Ondřej; Opálka, Lukáš; Vávrová, Kateřina

2017-05-01

Ceramides based on phytosphingosine, sphingosine and dihydrosphingosine are essential constituents of the skin lipid barrier that protects the body from excessive water loss. The roles of the individual ceramide subclasses in regulating skin permeability and the reasons for C4-hydroxylation of these sphingolipids are not completely understood. We investigated the chain length-dependent effects of dihydroceramides, sphingosine ceramides (with C4-unsaturation) and phytoceramides (with C4-hydroxyl) on the permeability, lipid organization and thermotropic behavior of model stratum corneum lipid membranes composed of ceramide/lignoceric acid/cholesterol/cholesteryl sulfate. Phytoceramides with very long C24 acyl chains increased the permeability of the model lipid membranes compared to dihydroceramides or sphingosine ceramides with the same chain lengths. Either unsaturation or C4-hydroxylation of dihydroceramides induced chain length-dependent increases in membrane permeability. Infrared spectroscopy showed that C4-hydroxylation of the sphingoid base decreased the relative ratio of orthorhombic chain packing in the membrane and lowered the miscibility of C24 phytoceramide with lignoceric acid. The phase separation in phytoceramide membranes was confirmed by X-ray diffraction. In contrast, phytoceramides formed strong hydrogen bonds and highly thermostable domains. Thus, the large heterogeneity in ceramide structures and in their aggregation mechanisms may confer resistance towards the heterogeneous external stressors that are constantly faced by the skin barrier. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of different alcohols on stratum corneum kallikrein 5 and phospholipase A2 together with epidermal keratinocytes and skin irritation.

PubMed

Cartner, T; Brand, N; Tian, K; Saud, A; Carr, T; Stapleton, P; Lane, M E; Rawlings, A V

2017-04-01

The aim of this exploratory study was to investigate the effect of ethanol, isopropanol and n-propanol on stratum corneum (SC) enzymes and keratinocytes in vitro together with their effects on skin condition and function. Activities of kallikrein 5 (KLK5) and phospholipase A2 (PLA2) as well as keratinocyte metabolic activity, interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α) were measured in vitro in the presence and absence of the different alcohols. We also measured transepidermal water loss (TEWL), skin capacitance, visual dryness and visual redness on the volar forearms of 25 Caucasian women following application of the alcohols 20 and 100 times per day over a period of 14 days in a clinical study. Reduced activities of KLK5 and PLA2 were observed in the presence of the alcohols. The greatest denaturing effect was always observed for n-propanol (P < 0.001), and in the case of PLA2, the effect of isopropanol was greater than ethanol (P < 0.001). Equally, ethanol had the mildest effects on keratinocyte metabolic activity and cytokine secretion (P < 0.001) and n-propanol always produced the most severe changes in normal and differentiated keratinocytes. These in vitro findings supported the clinical results where the major effects were on the induction of skin irritation (increased dropout rates) and ranked the intolerance of the different alcohols as follows: n-propanol > isopropanol > ethanol. At the high application frequencies, the effect of the different alcohols on transepidermal water loss (TEWL) and skin capacitance was similar, but at the low application frequencies, n-propanol had a significant effect on TEWL and capacitance values (P < 0.05). Equally, n-propanol and isopropanol produced significantly more skin redness at the low application frequencies. Clearly, isopropanol and n-propanol caused significant SC and keratinocyte perturbation in vitro together with damage to skin condition and function in vivo whereas ethanol

Thermotropic phase transitions in model membranes of the outer skin layer based on ceramide 6

NASA Astrophysics Data System (ADS)

Gruzinov, A. Yu.; Kiselev, M. A.; Ermakova, E. V.; Zabelin, A. V.

2014-01-01

The lipid intercellular matrix stratum corneum of the outer skin layer is a multilayer membrane consisting of a complex mixture of different lipids: ceramides, fatty acids, cholesterol, and its derivatives. The basis of the multilayer membrane is the lipid bilayer, i.e., a two-dimensional liquid crystal. Currently, it is known that the main way of substance penetration through the skin is the lipid matrix. The complexity of the actual biological system does not allow reliable direct study of its properties; therefore, system modeling is often used. Phase transitions in the lipid system whose composition simulates the native lipid matrix are studied by the X-ray synchrotron radiation diffraction method.

Reflectance spectroscopy can quantify cutaneous haemoglobin oxygenation by oxygen uptake from the atmosphere after epidermal barrier disruption.

PubMed

Heise, H M; Lampen, P; Stücker, M

2003-11-01

The supply of oxygen to the viable skin tissue within the upper layers is not only secured by the cutaneous blood vascular system, but to a significant part also by oxygen diffusion from the atmosphere through the horny layer. The aim of this study was to examine whether changes in haemoglobin oxygenation can be observed within the isolated perfused bovine udder skin used as a skin model by removing the upper horny layer by adhesive tape stripping. Diffuse reflectance spectroscopy in the visible spectral range was used for non-invasive characterisation of haemoglobin oxygenation in skin under in vitro conditions. Mid-infrared attenuated total reflectance spectroscopy was employed for analysing the surface layer of the stratum corneum with respect to keratin, water and lipid components. Skin barrier disruption was achieved by repeated stripping of superficial corneocyte layers by adhesive tape. Significant changes in skin haemoglobin oxygenation were observed for skin areas with reduced lipid concentration and a reduced stratum corneum layer, as determined from the quantitative evaluation of the diffuse reflectance skin spectra. The result can be interpreted as an increase of oxygen diffusion after the removal of the upper horny layer.

Sodium lauryl sulphate alters the mRNA expression of lipid-metabolizing enzymes and PPAR signalling in normal human skin in vivo.

PubMed

Törmä, Hans; Berne, Berit

2009-12-01

Detergents irritate skin and affect skin barrier homeostasis. In this study, healthy skin was exposed to 1% sodium lauryl sulphate (SLS) in water for 24 h. Biopsies were taken 6 h to 8 days post exposure. Lipid patterns were stained in situ and real-time polymerase chain reaction (PCR) was used to examine mRNA expression of enzymes synthesizing barrier lipids, peroxisome proliferator-activated receptors (PPAR) and lipoxygenases. The lipid pattern was disorganized from 6 h to 3 days after SLS exposure. Concomitant changes in mRNA expression included: (i) reduction, followed by induction, of ceramide-generating beta-glucocerebrosidase, (ii) increase on day 1 of two other enzymes for ceramide biosynthesis and (iii) persistent reduction of acetyl-CoA carboxylase-B, a key enzyme in fatty acid synthesis. Surprisingly, the rate-limiting enzyme in cholesterol synthesis, HMG-CoA reductase, was unaltered. Among putative regulators of barrier lipids synthesis, PPARalpha and PPARgamma exhibited reduced mRNA expression, while PPARbeta/delta and LXRbeta were unaltered. Epidermal lipoxygenase-3, which may generate PPARalpha agonists, exhibited reduced expression. In conclusion, SLS induces reorganization of lipids in the stratum corneum, which play a role in detergents' destruction of the barrier. The changes in mRNA expression of enzymes involved in synthesizing barrier lipids are probably important for the restoration of the barrier.

Variation of skin surface pH, sebum content and stratum corneum hydration with age and gender in a large Chinese population.

PubMed

Man, M Q; Xin, S J; Song, S P; Cho, S Y; Zhang, X J; Tu, C X; Feingold, K R; Elias, P M

2009-01-01

Evidence suggests the importance of skin biophysical properties in predicting diseases and in developing appropriate skin care. The results to date of studies on skin surface pH, stratum corneum (SC) hydration and sebum content in both genders and at various ages have been inconclusive, which was in part due to small sample size. Additionally, little is known about the skin physical properties of Asian, especially Chinese, subjects. In the present study, we assess the difference in skin surface pH, sebum content and SC hydration at various ages and in both genders in a large Chinese population without skin diseases. 713 subjects (328 males and 385 females) aged 0.5-94 years were enrolled in this study. The subjects were divided by age into 5 groups, i.e., 0-12, 13-35, 36-50, 51-70 and over 70 years old. A multifunctional skin physiology monitor was used to measure SC hydration, skin surface pH and sebum content on both the forehead and the forearms. In males, the highest sebum content was found on the forearm and the forehead in the age groups 36-50 (93.47 +/- 10.01 microg/cm(2)) and 51-70 years (9.16 +/- 1.95 microg/cm(2)), while in females, the highest sebum content was found on the forearm and the forehead in the age groups 13-35 (61.91 +/- 6.12 microg/cm(2)) and 51-70 years (7.54 +/- 2.55 microg/cm(2)). The forehead sebum content was higher in males aged 13-70 years than in age-matched females; the sebum content on the forehead in both males and females was higher than that on the forearm. Skin surface pH on the forehead of both males and females over the age of 70 years was higher than that in younger groups. SC hydration on the forehead in both males and females was lower above the age of 70, and the one in males aged 13-35 was higher than that in females (43.99 +/- 1.88 vs. 36.38 +/- 1.67 AU, p < 0.01). SC hydration on the forehead in both males and females did not significantly differ from that on the forearm. In a large Chinese cohort, the skin surface p

Er:YAG laser-induced changes in skin in vivo and transdermal drug delivery

NASA Astrophysics Data System (ADS)

Flock, Stephen T.; Stern, Tom; Lehman, Paul; Dinehart, Scott; Franz, Tom; Liu, George; Stern, Scott J.

1997-05-01

It has been shown that laser ablation of stratum corneum, in vitro, can result in an increased uptake of topically applied pharmaceuticals. We have performed measurements of drug permeation, using an in vitro model of human skin, that involves a portable Er:YAG laser used to ablate the stratum corneum. For the first time, this method of drug administration was tested in vivo in human volunteers, whereby a hydrocortisone blanching assay was used to assess the efficiency of the procedure. The results show that this is a safe and efficient way to ablate stratum corneum for the purpose of enhanced transcutaneous drug administration.

Solid lipid nanoparticles as carrier for sunscreens: in vitro release and in vivo skin penetration.

PubMed

Wissing, S A; Müller, R H

2002-06-17

The aim of this study was the comparison of two different formulations (solid lipid nanoparticles (SLN) and conventional o/w emulsion) as carrier systems for the molecular sunscreen oxybenzone. The influence of the carrier on the rate of release was studied in vitro with a membrane-free model. The release rate could be decreased by up to 50% with the SLN formulation. Further in vitro measurements with static Franz diffusion cells were performed. In vivo, penetration of oxybenzone into stratum corneum on the forearm was investigated by the tape stripping method. It was shown that the rate of release is strongly dependent upon the formulation and could be decreased by 30-60% in SLN formulations. In all test models, oxybenzone was released and penetrated into human skin more quickly and to a greater extent from the emulsions. The rate of release also depends upon the total concentration of oxybenzone in the formulation. In vitro-in vivo correlations could be made qualitatively.

In vivo confocal Raman spectroscopy study of the vitamin A derivative perfusion through human skin

NASA Astrophysics Data System (ADS)

dos Santos, Laurita; Téllez Soto, Claudio A.; Favero, Priscila P.; Martin, Airton A.

2016-03-01

In vivo confocal Raman spectroscopy is a powerful non-invasive technique able to analyse the skin constituents. This technique was applied to transdermal perfusion studies of the vitamin A derivative in human skin. The composition of the stratum corneum (lipid bilayer) is decisive for the affinity and transport of the vitamin through skin. The vitamin A is significantly absorbed by human skin when applied with water in oil emulsion or hydro-alcoholic gel. The purpose of this study is to elucidate the behaviour of vitamin A derivative into human skin without the presence of enhancers. The results showed that the intensity band of the derivative (around 1600 cm-1), which represents the -C=O vibrational mode, was detected in different stratum corneum depths (up to 20 μm). This Raman peak of vitamin A derivative has non-coincident band with the Raman spectra of the skin epidermis, demonstrating that compound penetrated in forearm skin.

SC lipid model membranes designed for studying impact of ceramide species on drug diffusion and permeation--part II: diffusion and permeation of model drugs.

PubMed

Ochalek, M; Podhaisky, H; Ruettinger, H-H; Wohlrab, J; Neubert, R H H

2012-10-01

The barrier function of two quaternary stratum corneum (SC) lipid model membranes, which were previously characterized with regard to the lipid organization, was investigated based on diffusion studies of model drugs with varying lipophilicities. Diffusion experiments of a hydrophilic drug, urea, and more lipophilic drugs than urea (i.e. caffeine, diclofenac sodium) were conducted using Franz-type diffusion cells. The amount of permeated drug was analyzed using either HPLC or CE technique. The subjects of interest in the present study were the investigation of the influence of physicochemical properties of model drugs on their diffusion and permeation through SC lipid model membranes, as well as the study of the impact of the constituents of these artificial systems (particularly ceramide species) on their barrier properties. The diffusion through both SC lipid model membranes and the human SC of the most hydrophilic model drug, urea, was faster than the permeation of the more lipophilic drugs. The slowest rate of permeation through SC lipid systems occurred in the case of caffeine. The composition of SC lipid model membranes has a significant impact on their barrier function. Model drugs diffused and permeated faster through Membrane II (presence of Cer [EOS]). In terms of the barrier properties, Membrane II is much more similar to the human SC than Membrane I. Copyright © 2012 Elsevier B.V. All rights reserved.

Study of magnetic silk fibroin nanoparticles for massage-like transdermal drug delivery

PubMed Central

Chen, Ai-Zheng; Chen, Lin-Qing; Wang, Shi-Bin; Wang, Ya-Qiong; Zha, Jun-Zhe

2015-01-01

A synergistic approach by the combination of magnetic nanoparticles with an alternating magnetic field for transdermal drug delivery was investigated. Methotrexate-loaded silk fibroin magnetic nanoparticles were prepared using suspension-enhanced dispersion by supercritical CO2. The physiochemical properties of the magnetic nanoparticles were characterized. In vitro studies on drug permeation across skin were performed under different magnetic fields in comparison with passive diffusion. The permeation flux enhancement factor was found to increase under a stationary magnetic field, while an alternating magnetic field enhanced drug permeation more effectively; the combination of stationary and alternating magnetic fields, which has a massage-like effect on the skin, achieved the best result. The mechanistic studies using attenuated total reflection Fourier-transform infrared spectroscopy demonstrate that an alternating magnetic field can change the ordered structure of the stratum corneum lipid bilayers from the gel to the lipid-crystalline state, which can increase the fluidity of the stratum corneum lipids, thus enhancing skin penetration. Compared with the other groups, the fluorescence signal with a bigger area detected in deeper regions of the skin also reveals that the simulated massage could enhance the drug permeation across the skin by increasing the follicular transport. The combination of magnetic nanoparticles with stationary/alternating magnetic fields has potential for effective massage-like transdermal drug delivery. PMID:26229467

Multiscale modeling of transdermal drug delivery

NASA Astrophysics Data System (ADS)

Rim, Jee Eun

2006-04-01

This study addresses the modeling of transdermal diffusion of drugs, to better understand the permeation of molecules through the skin, and especially the stratum corneum, which forms the main permeation barrier of the skin. In transdermal delivery of systemic drugs, the drugs diffuse from a patch placed on the skin through the epidermis to the underlying blood vessels. The epidermis is the outermost layer of the skin and can be further divided into the stratum corneum (SC) and the viable epidermis layers. The SC consists of keratinous cells (corneocytes) embedded in the lipid multi-bilayers of the intercellular space. It is widely accepted that the barrier properties of the skin mostly arises from the ordered structure of the lipid bilayers. The diffusion path, at least for lipophilic molecules, seems to be mainly through the lipid bilayers. Despite the advantages of transdermal drug delivery compared to other drug delivery routes such as oral dosing and injections, the low percutaneous permeability of most compounds is a major difficulty in the wide application of transdermal drug delivery. In fact, many transdermal drug formulations include one or more permeation enhancers that increase the permeation of the drug significantly. During the last two decades, many researchers have studied percutaneous absorption of drugs both experimentally and theoretically. However, many are based on pharmacokinetic compartmental models, in which steady or pseudo-steady state conditions are assumed, with constant diffusivity and partitioning for single component systems. This study presents a framework for studying the multi-component diffusion of drugs coupled with enhancers through the skin by considering the microstructure of the stratum corneum (SC). A multiscale framework of modeling the transdermal diffusion of molecules is presented, by first calculating the microscopic diffusion coefficient in the lipid bilayers of the SC using molecular dynamics (MD). Then a

Quantification of skin penetration of antioxidants of varying lipophilicity.

PubMed

Abla, M J; Banga, A K

2013-02-01

Antioxidants play a vital role in protecting the skin from environmental distress. As the skin is constantly exposed to harmful UV radiation, endogenous antioxidants present in the superficial layers of the skin neutralize reactive oxygen species. Over time, antioxidants become depleted and loss their protective effect on the skin. Therefore, supplementing skin with topical antioxidant can help replenish this loss and fight the oxidative stress. The objective of this study was to deliver antioxidants topically and quantify the amount permeated in the stratum corneum and underlying skin. Polyphenols (catechin, resveratrol and curcumin) and vitamin (retinol) with various lipophilic properties were delivered via porcine ear skin, using propylene glycol as a vehicle. The amount in the stratum corneum and underlying skin was quantified using tape stripping and skin extraction methods, respectively, and samples were analysed via HPLC. All four antioxidants permeated into the skin from the propylene glycol vehicle. The order of the amount of antioxidant in the stratum corneum was catechin > resveratrol~ retinol> curcumin, whereas that in the underlying skin was retinol > catechin~ resveratrol~ curcumin. Of the total amount of polyphenols in the skin, approximately 90% was retained in the stratum corneum whereas 10% was quantified in the underlying skin. In contrast, 10% of retinol was retained in the stratum corneum whereas 90% permeated in the underlying skin. Polyphenols (catechin, resveratrol and curcumin) showed high concentration in the stratum corneum whereas retinol showed high accumulation in the underlying layers of the skin. © 2012 The Authors ICS © 2012 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Progesterone lipid nanoparticles: Scaling up and in vivo human study.

PubMed

Esposito, Elisabetta; Sguizzato, Maddalena; Drechsler, Markus; Mariani, Paolo; Carducci, Federica; Nastruzzi, Claudio; Cortesi, Rita

2017-10-01

This investigation describes a scaling up study aimed at producing progesterone containing nanoparticles in a pilot scale. Particularly hot homogenization techniques based on ultrasound homogenization or high pressure homogenization have been employed to produce lipid nanoparticles constituted of tristearin or tristearin in association with caprylic-capric triglyceride. It was found that the high pressure homogenization method enabled to obtain nanoparticles without agglomerates and smaller mean diameters with respect to ultrasound homogenization method. X-ray characterization suggested a lamellar structural organization of both type of nanoparticles. Progesterone encapsulation efficiency was almost 100% in the case of high pressure homogenization method. Shelf life study indicated a double fold stability of progesterone when encapsulated in nanoparticles produced by the high pressure homogenization method. Dialysis and Franz cell methods were performed to mimic subcutaneous and skin administration. Nanoparticles constituted of tristearin in mixture with caprylic/capric triglyceride display a slower release of progesterone with respect to nanoparticles constituted of pure tristearin. Franz cell evidenced a higher progesterone skin uptake in the case of pure tristearin nanoparticles. A human in vivo study, based on tape stripping, was conducted to investigate the performance of nanoparticles as progesterone skin delivery systems. Tape stripping results indicated a decrease of progesterone concentration in stratum corneum within six hours, suggesting an interaction between nanoparticle material and skin lipids. Copyright © 2017 Elsevier B.V. All rights reserved.

Dynamic characterization of hydrophobic and hydrophilic solutes in oleic-acid enhanced transdermal delivery using two-photon fluorescence microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tseng, Te-Yu; Yang, Chiu-Sheng; Chen, Yang-Fang

In this letter, we propose an efficient methodology of investigating dynamic properties of sulforhodamine B and rhodamine B hexyl ester molecules transporting across ex-vivo human stratum corneum with and without oleic acid enhancement. Three-dimensional, time-lapse fluorescence images of the stratum corneum can be obtained using two-photon fluorescence microscopy. Furthermore, temporal quantifications of transport enhancements in diffusion parameters can be achieved with the use of Fick's second law. Dynamic characterization of solutes transporting across the stratum corneum is an effective method for understanding transient phenomena in transdermal delivery of probe molecules, leading to improved delivery strategies of molecular species for therapeuticmore » purposes.« less

Hand hygiene and skin health.

PubMed

Kownatzki, E

2003-12-01

The high rate of hand problems associated with the hand hygiene of medical professions is due to a combination of damaging factors: (1) the removal of barrier lipids by detergent cleaning and alcohol antisepsis followed by a loss of moisturizers and stratum corneum water and (2) the overhydration of the stratum corneum by sweat trapped within gloves. Together the facilitate the invasion of irritants and allergens which elicit inflammatory responses in the dermis. Among the lipids and water-soluble substances removed are natural antibacterials. Their loss leads to increased growth of transient and pathogenic micro-organisms which jeapordizes the very intention of skin hygiene. The kinetics of damage and its repair, and epidemiological evidence suggest that modern synthetic detergents as used in foaming liquid cleansers are the major offender. Conversely, the replacement of detergents with non-detergent emulsion cleansers has been shown to be effective in reducing the prevalence of hand problems among hospital staff. Presently recommended hand antisepsis reduces the risks to patients, but puts the burden on the health care provider. Rather than fighting micro-organisms at the expense of the skin's health, the skin and its own defences should be considered a collaborator in combating infectious diseases.

Variation of Skin Surface pH, Sebum Content and Stratum Corneum Hydration with Age and Gender in a Large Chinese Population

PubMed Central

Man, M.Q.; Xin, S.J.; Song, S.P.; Cho, S.Y.; Zhang, X.J.; Tu, C.X.; Feingold, K.R.; Elias, P.M.

2009-01-01

Background and Objectives Evidence suggests the importance of skin biophysical properties in predicting diseases and in developing appropriate skin care. The results to date of studies on skin surface pH, stratum corneum (SC) hydration and sebum content in both genders and at various ages have been inconclusive, which was in part due to small sample size. Additionally, little is known about the skin physical properties of Asian, especially Chinese, subjects. In the present study, we assess the difference in skin surface pH, sebum content and SC hydration at various ages and in both genders in a large Chinese population without skin diseases. Methods 713 subjects (328 males and 385 females) aged 0.5–94 years were enrolled in this study. The subjects were divided by age into 5 groups, i.e., 0–12, 13–35, 36–50, 51–70 and over 70 years old. A multifunctional skin physiology monitor was used to measure SC hydration, skin surface pH and sebum content on both the forehead and the forearms. Results In males, the highest sebum content was found on the forearm and the forehead in the age groups 36–50 (93.47 ± 10.01 μg/cm2) and 51–70 years (9.16 ± 1.95 μg/cm2), while in females, the highest sebum content was found on the forearm and the forehead in the age groups 13–35 (61.91 ± 6.12 μg/cm2) and 51–70 years (7.54 ± 2.55 μg/cm2). The forehead sebum content was higher in males aged 13–70 years than in age-matched females; the sebum content on the forehead in both males and females was higher than that on the forearm. Skin surface pH on the forehead of both males and females over the age of 70 years was higher than that in younger groups. SC hydration on the forehead in both males and females was lower above the age of 70, and the one in males aged 13–35 was higher than that in females (43.99 ± 1.88 vs. 36.38 ± 1.67 AU, p < 0.01). SC hydration on the forehead in both males and females did not significantly differ from that on the forearm

Analysis of epidermal lipids in normal and atopic dogs, before and after administration of an oral omega-6/omega-3 fatty acid feed supplement. A pilot study.

PubMed

Popa, Iuliana; Pin, Didier; Remoué, Noëlle; Remoué, Nathalie; Osta, Bilal; Callejon, Sylvie; Videmont, Emilie; Gatto, Hugues; Portoukalian, Jacques; Haftek, Marek

2011-12-01

Alterations of the lipid expression in the skin of human and canine atopic subjects may be one of the key factors in the disease development. We have analyzed the ultrastructure of the clinically uninvolved skin of atopic dogs and compared it with the lipid composition of their tape-stripped stratum corneum (SC). The effect of a 2 month treatment of atopic dogs by food supplementation with a mixture of essential fatty acids was evaluated on skin samples taken before and after the treatment period. Electron microscopy revealed that the non-lesional skin of atopic dogs exhibited an abnormal and largely incomplete structure of the lamellar lipids with little cohesion between the corneocyte strata. The SC of atopic dogs was characterized by a significant decrease in the lipid content when compared to the healthy controls. Following oral supplementation with the mixture of essential fatty acids, the overall lipid content of the SC markedly increased. This feature was observed both with the free and, most importantly, with the protein-bound lipids (cholesterol, fatty acids and ceramides), the latter constituting the corneocyte-bound scaffold for ordinate organisation of the extracellular lipid bi-layers. Indeed, the semi-quantitative electron microscopy study revealed that the treatment resulted in a significantly improved organization of the lamellar lipids in the lower SC, comparable to that of the healthy dogs. Our results indicate the potential interest of long-term alimentary supplementation with omega-6 and omega-3 essential fatty acids in canine atopic dermatitis.

Effects of topical corticosteroid and tacrolimus on ceramides and irritancy to sodium lauryl sulphate in healthy skin.

PubMed

Jungersted, Jakob Mutanu; Høgh, Julie K; Hellegren, Lars I; Jemec, Gregor B E; Agner, Tove

2011-05-01

The skin barrier, located in the stratum corneum, is influenced mainly by the lipid and protein composition of this layer. In eczematous diseases impairment of the skin barrier is thought to be of prime importance. Topical anti-inflammatory drugs and emollients are the most widely used eczema treatments. The aim of this study was to examine the effects of topically applied corticosteroid, tacrolimus and emollient on stratum corneum lipids and barrier parameters. Nineteen healthy volunteers participated in the study. Both forearms of the subjects were divided into four areas, which were treated twice daily for one week with betamethasone, tacrolimus, emollient, or left untreated, respectively. After one week each area was challenged with a 24 h sodium lauryl sulphate patch test. The lipids were collected using the cyanoacrylate method and evaluated by high performance thin layer chromatography. For evaluation of the skin barrier, transepidermal water loss, erythema and electrical capacitance were measured. The ceramide/cholesterol ratio was increased in betamethasone- (p = 0.008) and tacrolimus-treated (p = 0.025) skin compared with emollient-treated skin. No differences in ceramide subgroups were found between treatment regimes. Pretreatment with betamethasone (p = 0.01) or with tacrolimus (p = 0.001) causes a decreased inflammatory response to sodium lauryl sulphate compared with emollient. In conclusion, treatment with betamethasone and tacrolimus has a positive effect on the ceramide/cholesterol ratio and susceptibility to irritant reaction compared with an emollient.

Application of Gelidium corneum edible films containing carvacrol for ham packages.

PubMed

Lim, G O; Hong, Y H; Song, K B

2010-01-01

We prepared an edible film of Gelidium corneum (GC) containing carvacrol as an antimicrobial and antioxidative agent. The GC film containing carvacrol significantly decreased the WVP, while TS and %E values were increased, compared to the film without carvacrol. Increasing amounts of an antimicrobial agent increased antimicrobial activity against Escherichia coli O157:H7 and Listeria monocytogenes. Application of the film to ham packaging successfully inhibited the microbial growth and lipid oxidation of ham during storage. Our results indicate that GC film can be a useful edible packaging material for food products, and the incorporation of carvacrol in the GC film may extend the shelf life.

Matriptase initiates epidermal prokallikrein activation and disease onset in a mouse model of Netherton syndrome

PubMed Central

Sales, Katiuchia Uzzun; Masedunskas, Andrius; Bey, Alexandra L.; Rasmussen, Amber; Weigert, Roberto; List, Karin; Szabo, Roman; Overbeek, Paul A.; Bugge, Thomas H.

2010-01-01

Deficiency in the serine protease inhibitor LEKTI is the etiological origin of Netherton syndrome. The principal morbidities of the disease are stratum corneum detachment and chronic inflammation. We show that the membrane protease, matriptase, initiates Netherton syndrome in a LEKTI-deficient mouse model by premature activation of a pro-kallikrein-related cascade. Auto-activation of pro-inflammatory and stratum corneum detachment-associated pro-kallikrein-related peptidases was either low or undetectable, but they were efficiently activated by matriptase. Ablation of matriptase from LEKTI-deficient mice dampened inflammation, eliminated aberrant protease activity, prevented stratum corneum detachment, and improved epidermal barrier function. The study uncovers a pathogenic matriptase-pro-kallikrein pathway that could be operative in several human skin and inflammatory diseases. PMID:20657595

Qualitative and Quantitative Study of the Potential of Lipid Nanocapsules of One Hundred Twenty Nanometers for the Topical Administration of Hydrophobic Molecules.

PubMed

Nguyen, Hoang Truc Phuong; Munnier, Emilie; Perse, Xavier; Vial, Francis; Yvergnaux, Florent; Perrier, Thomas; Soucé, Martin; Chourpa, Igor

2016-10-01

In this study, we evaluated the potential of lipid nanocapsules (LNC) of 120 nm as drug nanocarriers to treat skin diseases. As a model molecule, we encapsulated the fluorescent dye curcumin, which also is an antioxidant. Curcumin-loaded LNC showed interesting antioxidant properties and a low toxicity on human skin cells. The penetration of curcumin in the skin was determined by 2 complementary methods: high performance liquid chromatography was used to measure total curcumin accumulation in the skin, whereas fluorescence confocal spectral imaging of skin sections showed that curcumin preferentially accumulates in the stratum corneum and the viable epidermis. These results confirm that LNC of a size above 100 nm can vectorize hydrophobic compounds to the keratinocytes without transdermal delivery. They also demonstrate the interest of combining 2 analytical methods when studying the skin penetration of nanovectorized molecules. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Epidermal hydration and skin surface lipids in patients with long-term complications of sulfur mustard poisoning.

PubMed

Layegh, Pouran; Maleki, Masoud; Mousavi, Seyed Reza; Yousefzadeh, Hadis; Momenzadeh, Akram; Golmohammadzadeh, Shiva; Balali-Mood, Mahdi

2015-07-01

Despite almost the three decades passed since the chemical attacks of Iraqi's army against the Iranian troops, some veterans are still suffering from long-term complications of sulfur mustard (SM) poisoning, including certain skin complaints specially dryness, burning, and pruritus. We thus aimed to evaluate the skin's water and lipid content in patients with a disability of >25% due to complications of SM poisoning and compare them with a matched control group. Sixty-nine male participants were included in this study; 43 SM-exposed patients, and 26 normal controls from their close relatives. The water and lipid content was measured in four different locations: Extensor and flexor sides of forearms and lateral and medial sides of legs by the Corneometer CM 820/Sebumeter SM 810. Collected data was analyzed and P ≤ 0.05 was considered as statistically significant. The mean age of the patients and controls was 49.53 ± 11.34 (ranges: 40-71) and 29.08 ± 8.836 (ranges: 15-49 years), respectively. In the veterans group, the main cutaneous complaint was itching and skin dryness. Cherry angioma, dry skin, and pruritus were significantly more common in the SM-exposed cases than in the controls. (P = 0.01, 0.05, and 0.04, respectively). The moisture and lipid content of all areas were lower in the SM-exposed group, but it was only significant in skin sebum of lateral sides of legs (P = 0.02). Exposure to SM could decrease the function of stratum corneum and lipid production as a barrier, even after several years of its exposure.

Squalene-containing nanostructured lipid carriers promote percutaneous absorption and hair follicle targeting of diphencyprone for treating alopecia areata.

PubMed

Lin, Yin-Ku; Al-Suwayeh, Saleh A; Leu, Yann-Lii; Shen, Feng-Ming; Fang, Jia-You

2013-02-01

Diphencyprone (DPCP) is a therapeutic agent for treating alopecia areata. To improve skin absorption and follicular targeting nanostructured lipid carriers (NLCs) were developed. Nanoparticles were characterized by size, zeta potential, molecular environment, differential scanning calorimetry (DSC), and nuclear magnetic resonance (NMR). In vitro and in vivo skin absorption experiments were performed. Fluorescence and confocal microscopes for imaging skin distribution were used. NLCs with different designs were 208 ~ 265 nm with  > 77% DPCP encapsulation. NLCs incorporating a cationic surfactant or more soybean phosphatidylcholine (SPC) showed higher lipophilicity compared to typical NLCs by Nile red emission. All NLCs tested revealed controlled DPCP release; burst release was observed for control. The formulation with more SPC provided 275 μg/g DPCP skin retention, which was greater than control and other NLCs. Intersubject deviation was reduced after DPCP loading into NLCs. Cyanoacrylate skin biopsy demonstrated greater follicular deposition for NLCs with more SPC compared to control. Cationic NLCs but not typical or SPC-containing carriers were largely internalized into keratinocytes. In vivo skin retention of NLCs with more SPC was higher than free control. Confocal imaging confirmed localization of NLCs in follicles and intercellular lipids of stratum corneum. This work encourages further investigation of DPCP absorption using NLCs with a specific formulation design.

Skin hydration and lifestyle-related factors in community-dwelling older people.

PubMed

Iizaka, Shinji

2017-09-01

This study aimed to investigate skin hydration status of the lower legs by comparing several methods and examining lifestyle-related factors in community-dwelling older people. A cross-sectional study was conducted in three community settings in Japan from autumn to winter. Participants were older people aged ≥65 years (n=118). Skin hydration status of the lower legs was evaluated by stratum corneum hydration using an electrical device, clinical symptoms by an expert's observation and the visual analogue scale. Lifestyle factors of skin care were evaluated by a self-administered questionnaire. The mean age of participants was 74.4 years and 83.9% were women. Stratum corneum hydration was significantly correlated with clinical scores by an expert's observation (rho=-0.46, P<0.001), but it was not correlated with the visual analogue scale (rho=-0.08, P=0.435). Among participants who did not perceive dry skin, 57.5% showed low stratum corneum hydration. Hospitalization in the past year (b=-9.4, P=0.008), excessive bathing habits (b=-4.6, P=0.014), and having an outdoor hobby (b=-5.7, P=0.007) were negatively associated, and diuretics (b=11.5, P=0.002) and lotion-type moisturizer use (b=4.6, P=0.022) were positively associated with stratum corneum hydration. Stratum corneum hydration measurements show an adequate association with observation-based evaluation by an expert, but poor agreement with subjective evaluation in community-dwelling older people. Hospitalization experience and lifestyle factors are associated with skin hydration. Copyright © 2017 Elsevier B.V. All rights reserved.

Skin penetration and kinetics of pristine fullerenes (C{sub 60}) topically exposed in industrial organic solvents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xia, Xin R., E-mail: xia@ncsu.ed; Monteiro-Riviere, Nancy A.; Riviere, Jim E.

2010-01-01

Pristine fullerenes (C{sub 60}) in different solvents will be used in many industrial and pharmaceutical manufacturing and derivatizing processes. This report explores the impact of solvents on skin penetration of C{sub 60} from different types of industrial solvents (toluene, cyclohexane, chloroform and mineral oil). Yorkshire weanling pigs (n = 3) were topically dosed with 500 muL of 200 mug/mL C{sub 60} in a given solvent for 24 h and re-dosed daily for 4 days to simulate the worst scenario in occupational exposures. The dose sites were tape-stripped and skin biopsies were taken after 26 tape-strips for quantitative analysis. When dosedmore » in toluene, cyclohexane or chloroform, pristine fullerenes penetrated deeply into the stratum corneum, the primary barrier of skin. More C{sub 60} was detected in the stratum corneum when dosed in chloroform compared to toluene or cyclohexane. Fullerenes were not detected in the skin when dosed in mineral oil. This is the first direct evidence of solvent effects on the skin penetration of pristine fullerenes. The penetration of C{sub 60} into the stratum corneum was verified using isolated stratum corneum in vitro; the solvent effects on the stratum corneum absorption of C{sub 60} were consistent with those observed in vivo. In vitro flow-through diffusion cell experiments were conducted in pig skin and fullerenes were not detected in the receptor solutions by 24 h. The limit of detection was 0.001 mug/mL of fullerenes in 2 mL of the receptor solutions.« less

Sample allocation balancing overall representativeness and stratum precision.

PubMed

Diaz-Quijano, Fredi Alexander

2018-05-07

In large-scale surveys, it is often necessary to distribute a preset sample size among a number of strata. Researchers must make a decision between prioritizing overall representativeness or precision of stratum estimates. Hence, I evaluated different sample allocation strategies based on stratum size. The strategies evaluated herein included allocation proportional to stratum population; equal sample for all strata; and proportional to the natural logarithm, cubic root, and square root of the stratum population. This study considered the fact that, from a preset sample size, the dispersion index of stratum sampling fractions is correlated with the population estimator error and the dispersion index of stratum-specific sampling errors would measure the inequality in precision distribution. Identification of a balanced and efficient strategy was based on comparing those both dispersion indices. Balance and efficiency of the strategies changed depending on overall sample size. As the sample to be distributed increased, the most efficient allocation strategies were equal sample for each stratum; proportional to the logarithm, to the cubic root, to square root; and that proportional to the stratum population, respectively. Depending on sample size, each of the strategies evaluated could be considered in optimizing the sample to keep both overall representativeness and stratum-specific precision. Copyright © 2018 Elsevier Inc. All rights reserved.

Gravimetric analysis and differential scanning calorimetric studies on glycerin-induced skin hydration.

PubMed

Lee, Ae-Ri Cho; Moon, Hee Kyung

2007-11-01

A thermal gravimetric analysis (TGA) and a differential scanning calorimetry (DSC) were carried out to characterize the water property and an alteration of lipid phase transition of stratum corneum (SC) by glycerin. In addition, the relationship between steady state skin permeation rate and skin hydration in various concentrations of glycerin was investigated. Water vapor absorption-desorption was studied in the hairless mouse stratum corneum. Dry SC samples were exposed to different conc. of glycerin (0-50%) followed by exposure to dry air and the change in weight property was monitored over time by use of TGA. In DSC study, significant decrease in DeltaH of the lipid transition in 10% glycerin and water treated sample: the heat of lipid transition of normal, water, 10% glycerin treated SC were 6.058, 4.412 and 4.316 mJ/mg, respectively. In 10% glycerin treated SCs, the Tc of water shifts around 129 degrees C, corresponding to the weakly bound secondary water. In 40% glycerin treated SC, the Tc of water shifts to 144 degrees C corresponding to strongly bound primary water. There was a good correlation between the hydration property of the skin and the steady state skin flux with the correlation coefficient (r2=0.94). As the hydration increased, the steady state flux increased. As glycerin concentration increased, hydration property decreased. High diffusivity induced by the hydration effect of glycerin and water could be the major contributing factor for the enhanced skin permeation of nicotinic acid (NA).

Gravimetric method for in vitro calibration of skin hydration measurements.

PubMed

Martinsen, Ørjan G; Grimnes, Sverre; Nilsen, Jon K; Tronstad, Christian; Jang, Wooyoung; Kim, Hongsig; Shin, Kunsoo; Naderi, Majid; Thielmann, Frank

2008-02-01

A novel method for in vitro calibration of skin hydration measurements is presented. The method combines gravimetric and electrical measurements and reveals an exponential dependency of measured electrical susceptance to absolute water content in the epidermal stratum corneum. The results also show that absorption of water into the stratum corneum exhibits three different phases with significant differences in absorption time constant. These phases probably correspond to bound, loosely bound, and bulk water.

Recent advances in X-ray microanalysis in dermatology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Forslind, B.; Grundin, T.G.; Lindberg, M.

1985-01-01

Electron microprobe and proton microprobe X-ray analysis can be used in several areas of dermatological research. With a proton probe, the distribution of trace elements in human hair can be determined. Electron microprobe analysis on freeze-dried cryosections of guinea-pig and human epidermis shows a marked gradient of Na, P and K over the stratum granulosum. In sections of freeze-substituted human skin this gradient is less steep. This difference is likely to be due to a decrease in water content of the epidermis towards the stratum corneum. Electron microprobe analysis of the epidermis can, for analysis of trace elements, be complementedmore » by the proton microprobe. Quantitative agreement between the two techniques can be obtained by the use of a standard. Proton microprobe analysis was used to determine the distribution of Ni or Cr in human epidermis exposed to nickel or chromate ions. Possible differences in water content between the stratum corneum of patients with atopic eczema and normal stratum corneum was investigated in skin freeze-substituted with Br-doped resin. No significant differences were observed.« less

Development of terbinafine solid lipid nanoparticles as a topical delivery system

PubMed Central

Chen, Ying-Chen; Liu, Der-Zen; Liu, Jun-Jen; Chang, Tsung-Wei; Ho, Hsiu-O; Sheu, Ming-Thau

2012-01-01

To resolve problems of long treatment durations and frequent administration of the antifungal agent terbinafine (TB), solid lipid nanoparticles (SLNs) with the ability to load lipophilic drugs and nanosize were developed. The SLNs were manufactured by a microemulsion technique in which glyceryl monostearate (GMS), glyceryl behenate (Compritol® 888; Gattefossé), and glyceryl palmitostearate (Precirol® ATO 5; Gattefossé) were used as the solid lipid phases, Tween® and Cremophor® series as the surfactants, and propylene glycol as the cosurfactant to construct ternary phase diagrams. The skin of nude mice was used as a barrier membrane, and penetration levels of TB of the designed formulations and a commercial product, Lamisil® Once™ (Novartis Pharmaceuticals), in the stratum corneum (SC), viable epidermis, and dermis were measured; particle sizes were determined as an indicator of stability. The optimal SLN system contained a <5% lipid phase and >50% water phase. The addition of ethanol or etchants had no significant effect on enhancing the amount of TB that penetrated the skin layers, but it was enhanced by increasing the percentage of the lipid phase. Furthermore, the combination of GMS and Compritol® 888 was able to increase the stable amount of TB that penetrated all skin layers. For the ACP1-GM1 (4% lipid phase; Compritol® 888: GMS of 1:1) formulation, the amount of TB that penetrated the SC was similar to that of Lamisil® Once™, whereas the amount of TB of the dermis was higher than that of Lamisil® Once™ at 12 hours, and it was almost the same as that of Lamisil® Once™ at 24 hours. It was concluded that the application of ACP1-GM1 for 12 hours might have an efficacy comparable to that of Lamisil® Once™ for 24 hours, which would resolve the practical problem of the longer administration period that is necessary for Lamisil® Once™. PMID:22923986

Oral administration of Bifidobacterium breve attenuates UV-induced barrier perturbation and oxidative stress in hairless mice skin.

PubMed

Ishii, Yuki; Sugimoto, Saho; Izawa, Naoki; Sone, Toshiro; Chiba, Katsuyoshi; Miyazaki, Kouji

2014-07-01

Recent studies have shown that some probiotics affect not only the gut but also the skin. However, the effects of probiotics on ultraviolet (UV)-induced skin damage are poorly understood. In this study, we aim to examine whether oral administration of live Bifidobacterium breve strain Yakult (BBY), a typical probiotic, can attenuate skin barrier perturbation caused by UV and reactive oxygen species (ROS) in hairless mice. The mice were orally supplemented with a vehicle only or BBY once a day for nine successive days. Mouse dorsal skin was irradiated with UV from days 6 to 9. The day after the final irradiation, the transepidermal water loss (TEWL), stratum corneum hydration, and oxidation-related factors of the skin were evaluated. We elucidated that BBY prevented the UV-induced increase in TEWL and decrease in stratum corneum hydration. In addition, BBY significantly suppressed the UV-induced increase in hydrogen peroxide levels, oxidation of proteins and lipids, and xanthine oxidase activity in the skin. Conversely, antioxidant capacity did not change regardless of whether BBY was administered or not. In parameters we evaluated, there was a positive correlation between the increase in TEWL and the oxidation levels of proteins and lipids. Our results suggest that oral administration of BBY attenuates UV-induced barrier perturbation and oxidative stress of the skin, and this antioxidative effect is not attributed to enhancement of antioxidant capacity but to the prevention of ROS generation.

Detecting electroporation by assessing the time constants in the exponential response of human skin to voltage controlled impulse electrical stimulation.

PubMed

Bîrlea, Sinziana I; Corley, Gavin J; Bîrlea, Nicolae M; Breen, Paul P; Quondamatteo, Fabio; OLaighin, Gearóid

2009-01-01

We propose a new method for extracting the electrical properties of human skin based on the time constant analysis of its exponential response to impulse stimulation. As a result of this analysis an adjacent finding has arisen. We have found that stratum corneum electroporation can be detected using this analysis method. We have observed that a one time-constant model is appropriate for describing the electrical properties of human skin at low amplitude applied voltages (<30V), and a two time-constant model best describes skin electrical properties at higher amplitude applied voltages (>30V). Higher voltage amplitudes (>30V) have been proven to create pores in the skin's stratum corneum which offer a new, lower resistance, pathway for the passage of current through the skin. Our data shows that when pores are formed in the stratum corneum they can be detected, in-vivo, due to the fact that a second time constant describes current flow through them.

Assessment of dermatopharmacokinetic approach in the bioequivalence determination of topical tretinoin gel products.

PubMed

Pershing, Lynn K; Nelson, Joel L; Corlett, Judy L; Shrivastava, Surendra P; Hare, Don B; Shah, Vinod P

2003-05-01

A new dermatopharmacokinetic (DPK) approach has been proposed for bioequivalence determination of topical drug products by comparing the drug content kinetics in stratum corneum. We sought to establish any correlation between clinical safety/efficacy and DPK approach in bioequivalence determination of tretinoin gel 0.025%. Tretinoin and isotretinoin were quantified in human volar forearm stratum corneum as a function of time with 3 tretinoin gel 0.025% products in 49 patients. Stratum corneum layers were harvested using multiple adhesive disks, which were subsequently extracted and quantified for both isomers by high-performance liquid chromatography. Products with similar composition and therapeutic equivalence were found bioequivalent, and products with different composition and clinical profiles were found bioinequivalent by DPK methodology. There is a direct correlation between DPK parameters in healthy patients and clinical safety/efficacy of tretinoin gel products in patients with acne. Data support the use of DPK parameters and methodology in the bioequivalence assessment of topical tretinoin gel products.

Enhanced skin penetration of lidocaine through encapsulation into nanoethosomes and nanostructured lipid carriers: a comparative study.

PubMed

Babaei, S; Ghanbarzadeh, S; Adib, Z M; Kouhsoltani, M; Davaran, S; Hamishehkar, H

2016-05-01

Lipid based nanoparticles have become a major research object in topical drug delivery to enable drugs to pass the stratum corneum and reach the desired skin layer. The present investigation deals with the encapsulation of lidoacine into nanostructured lipid carriers (NLCs) and nanoethosomes for improving its dermal delivery and consequently local anesthetic efficacy. Concurrently these two topical delivery systems were compared. Lidocaine-loaded NLCs and nanoethosomes were characterized by various techniques and used for an in vitro skin penetration study using excised rat skin and Franz diffusion cells. The nanoparticles were tracked in the skin by following the Rhodamine-labled nanocarriers under fluorescent microscopy. Optimized lidocaine-loaded NLCs (size 96 nm, zeta potential -13.7 mV, encapsulation efficiency (EE) % 69.86% and loading capacity (LC) % 10.47%) and nanoethosomes (size 105.4 nm, zeta potential -33.6 mV, EE 40.14% and LC 8.02%) were chosen for a skin drug delivery study. Higher skin drug deposition of NLCs and nanoethosomal formulations compared to lidocaine hydroalcoholic solution represented a better localization of the drug in the skin. NLC formulation showed the lowest entered drug in the receptor phase of Franz diffusion cell in comparison with nanoethosomes and hydroalcoholic solution confirming the highest skin accumulation of drug. Both colloidal systems showed superiority over the drug solution for dermal delivery of lidocaine, however, NLC exhibited more promising characteristics than nanoethosomes regarding drug loading and skin targeted delivery.

Canine epidermal lipid sampling by skin scrub revealed variations between different body sites and normal and atopic dogs

PubMed Central

2014-01-01

Background Previously, we evaluated a minimally invasive epidermal lipid sampling method called skin scrub, which achieved reproducible and comparable results to skin scraping. The present study aimed at investigating regional variations in canine epidermal lipid composition using the skin scrub technique and its suitability for collecting skin lipids in dogs suffering from certain skin diseases. Eight different body sites (5 highly and 3 lowly predisposed for atopic lesions) were sampled by skin scrub in 8 control dogs with normal skin. Additionally, lesional and non-lesional skin was sampled from 12 atopic dogs and 4 dogs with other skin diseases by skin scrub. Lipid fractions were separated by high performance thin layer chromatography and analysed densitometrically. Results No significant differences in total lipid content were found among the body sites tested in the control dogs. However, the pinna, lip and caudal back contained significantly lower concentrations of ceramides, whereas the palmar metacarpus and the axillary region contained significantly higher amounts of ceramides and cholesterol than most other body sites. The amount of total lipids and ceramides including all ceramide classes were significantly lower in both lesional and non-lesional skin of atopic dogs compared to normal skin, with the reduction being more pronounced in lesional skin. The sampling by skin scrub was relatively painless and caused only slight erythema at the sampled areas but no oedema. Histological examinations of skin biopsies at 2 skin scrubbed areas revealed a potential lipid extraction from the transition zone between stratum corneum and granulosum. Conclusions The present study revealed regional variations in the epidermal lipid and ceramide composition in dogs without skin abnormalities but no connection between lipid composition and predilection sites for canine atopic dermatitis lesions. The skin scrub technique proved to be a practicable sampling method for canine

Efficacy of a shower cream and a lotion with skin-identical lipids in healthy subjects with atopic dry skin.

PubMed

Berardesca, Enzo; Mortillo, Susan; Cameli, Norma; Ardigo, Marco; Mariano, Maria

2018-05-10

Atopic dermatitis is a chronic, pruritic inflammatory skin disease that adversely affects quality of life. The current study evaluates the efficacy of a shower cream and a lotion, each with skin-identical lipids and emollients, in the treatment of atopic dry skin of subjects with a history of atopic condition. In all, 40 healthy females with clinically dry skin on the lower legs were enrolled in the study and underwent 4 weeks of daily use of the shower cream and 2 additional weeks of both the shower cream and the body lotion. Subjects were evaluated at day 0, week 4, and week 6. Skin barrier function was assessed by Tewameter ® , skin hydration by Corneometer ® , smoothness and desquamation by Visioscan ® , and stratum corneum architecture by reflectance confocal microscopy (RCM). The investigator assessed the degree of dryness, roughness, redness, cracks, tingling and itch, and subjective self-assessment evaluated the perception of skin soothing, smoothness, and softness. Skin barrier function and skin moisture maintenance were significantly improved using the shower cream. The lotion with physiological lipids, together with the shower cream, also improved skin barrier function and moisture. Both the shower cream and the body lotion reduced clinical dryness, roughness, redness, cracks, tingling and itch, according to the dermatologist, and increased soothing, smoothness, and softness, according to the subjects of the study. The combination of a shower cream and a lotion with physiological lipids efficiently restores skin barrier function and increases skin hydration, becoming an effective skin-care option for patients with atopic dry skin. © 2018 Wiley Periodicals, Inc.

Probing the role of ceramide hydroxylation in skin barrier lipid models by 2H solid-state NMR spectroscopy and X-ray powder diffraction.

PubMed

Kováčik, Andrej; Vogel, Alexander; Adler, Juliane; Pullmannová, Petra; Vávrová, Kateřina; Huster, Daniel

2018-05-01

In this work, we studied model stratum corneum lipid mixtures composed of the hydroxylated skin ceramides N-lignoceroyl 6-hydroxysphingosine (Cer[NH]) and α-hydroxylignoceroyl phytosphingosine (Cer[AP]). Two model skin lipid mixtures of the composition Cer[NH] or Cer[AP], N-lignoceroyl sphingosine (Cer[NS]), lignoceric acid (C24:0) and cholesterol in a 0.5:0.5:1:1 molar ratio were compared. Model membranes were investigated by differential scanning calorimetry and 2 H solid-state NMR spectroscopy at temperatures from 25 °C to 80 °C. Each component of the model mixture was specifically deuterated for selective detection by 2 H NMR. Thus, the exact phase composition of the mixture at varying temperatures could be quantified. Moreover, using X-ray powder diffraction we investigated the lamellar phase formation. From the solid-state NMR and DSC studies, we found that both hydroxylated Cer[NH] and Cer[AP] exhibit a similar phase behavior. At physiological skin temperature of 32 °C, the lipids form a crystalline (orthorhombic) phase. With increasing temperature, most of the lipids become fluid and form a liquid-crystalline phase, which converts to the isotropic phase at higher temperatures (65-80 °C). Interestingly, lignoceric acid in the Cer[NH]-containing mixture has a tendency to form two types of fluid phases at 65 °C. This tendency was also observed in Cer[AP]-containing membranes at 80 °C. While Cer[AP]-containing lipid models formed a short periodicity phase featuring a repeat spacing of d = 5.4 nm, in the Cer[NH]-based model skin lipid membranes, the formation of unusual long periodicity phase with a repeat spacing of d = 10.7 nm was observed. Copyright © 2018 Elsevier B.V. All rights reserved.

Ex vivo skin absorption of terpenes from Vicks VapoRub ointment.

PubMed

Cal, Krzysztof; Sopala, Monika

2008-08-01

The pharmaceutical market offers a wide range of inhalant drug products applied on the skin that contain essential oils and/or their isolated compounds, i.e. terpenes. Because there are few data concerning the skin penetration of terpenes, especially from complex carriers, the goal of this study was to determine the ex vivo skin absorption kinetics of chosen terpenes, namely eucalyptol, menthol, camphor, alpha-pinene, and beta-pinene, from the product Vicks VapoRub. Human cadaver skin was placed in a flow-through diffusion chamber and the product was applied for 15, 30, and 60 min. After the application time the skin was separated into layers using a tape-stripping technique: three fractions of stratum corneum and epidermis with dermis, and terpenes amounts in the samples were determined by gas-chromatography. The investigated terpenes showed different absorption characteristics related to their physicochemical properties and did not permeate through the skin into the acceptor fluid. Eucalyptol had the largest total accumulation in the stratum corneum and in the epidermis with dermis, while alpha-pinene penetrated into the skin in the smallest amount. The short time in which saturation of the stratum corneum with the terpenes occurred and the high accumulation of most of the investigated terpenes in the skin layers proved that these compounds easily penetrate and permeate the stratum corneum and that in vivo they may easily penetrate into the blood circulation.

Biochemical enhancement of transdermal delivery with magainin peptide: modification of electrostatic interactions by changing pH.

PubMed

Kim, Yeu-Chun; Late, Sameer; Banga, Ajay K; Ludovice, Peter J; Prausnitz, Mark R

2008-10-01

Magainin is a naturally occurring, pore-forming peptide that has recently been shown to increase skin permeability. This study tested the hypothesis that electrostatic forces between magainin peptides and drugs mediate drug transport across the skin. Electrostatic interaction between positively charged magainin and a negatively charged model drug, fluorescein, was attractive at pH 7.4 and resulted in a 35-fold increase in delivery across human epidermis in vitro when formulated with 2% N-lauroylsarcosine in 50% ethanol. Increasing to pH 10 or 11 largely neutralized magainin's charge, which eliminated enhancement due to magainin. Shielding electrostatic interactions with 1-2M NaCl solution similarly eliminated enhancement. Showing the opposite dependence on pH, electrostatic interaction between magainin and a positively charged anti-nausea drug, granisetron, was largely neutralized at pH 10 and resulted in a 92-fold increase in transdermal delivery. Decreasing to pH 5 increased magainin's positive charge, which repelled granisetron and progressively decreased transdermal flux. Circular dichroism analysis, multi-photon microscopy, and FTIR spectroscopy showed no significant pH effect on magainin secondary structure, magainin deposition in stratum corneum, or stratum corneum lipid order, respectively. We conclude that magainin increases transdermal delivery by a mechanism involving electrostatic interaction between magainin peptides and drugs.

Biochemical enhancement of transdermal delivery with magainin peptide: Modification of electrostatic interactions by changing pH

PubMed Central

Kim, Yeu-Chun; Late, Sameer; Banga, Ajay K.; Ludovice, Peter J.; Prausnitz, Mark R.

2008-01-01

Magainin is a naturally occurring, pore-forming peptide that has recently been shown to increase skin permeability. This study tested the hypothesis that electrostatic forces between magainin peptides and drugs mediate drug transport across the skin. Electrostatic interaction between positively charged magainin and a negatively charged model drug, fluorescein, was attractive at pH 7.4 and resulted in a 35 fold increase in delivery across human epidermis in vitro when formulated with 2% N-lauroylsarcosine in 50% ethanol. Increasing to pH 10 or 11 largely neutralized magainin’s charge, which eliminated enhancement due to magainin. Shielding electrostatic interactions with 1–2 M NaCl solution similarly eliminated enhancement. Showing the opposite dependence on pH, electrostatic interaction between magainin and a positively charged anti-nausea drug, granisetron, was largely neutralized at pH 10 and resulted in a 59 fold increase in transdermal delivery. Decreasing to pH 5 increased magainin’s positive charge, which repelled granisetron and progressively decreased transdermal flux. Circular dichroism analysis, multi-photon microscopy, and FTIR spectroscopy showed no significant pH effect on magainin secondary structure, magainin deposition in stratum corneum, or stratum corneum lipid order, respectively. We conclude that magainin increases transdermal delivery by a mechanism involving electrostatic interaction between magainin peptides and drugs. PMID:18601987

Volumetric Visualization of Human Skin

NASA Astrophysics Data System (ADS)

Kawai, Toshiyuki; Kurioka, Yoshihiro

We propose a modeling and rendering technique of human skin, which can provide realistic color, gloss and translucency for various applications in computer graphics. Our method is based on volumetric representation of the structure inside of the skin. Our model consists of the stratum corneum and three layers of pigments. The stratum corneum has also layered structure in which the incident light is reflected, refracted and diffused. Each layer of pigment has carotene, melanin or hemoglobin. The density distributions of pigments which define the color of each layer can be supplied as one of the voxel values. Surface normals of upper-side voxels are fluctuated to produce bumps and lines on the skin. We apply ray tracing approach to this model to obtain the rendered image. Multiple scattering in the stratum corneum, reflective and absorptive spectrum of pigments are considered. We also consider Fresnel term to calculate the specular component for glossy surface of skin. Some examples of rendered images are shown, which can successfully visualize a human skin.

When to suspect tinea; a histopathologic study of 103 cases of PAS-positive tinea.

PubMed

Elbendary, Amira; Valdebran, Manuel; Gad, AbdAllah; Elston, Dirk M

2016-10-01

The histopathologic features of tinea vary widely and its diagnosis could be easily missed if the index of suspicion is not high. We aimed in this study to detect histopathologic features that could be a clue for diagnosis We retrospectively reviewed 103 cases of tinea, confirmed by Periodic acid-Schiff (PAS) staining. For each case, gender, biopsy site, and pre-biopsy suspicion were recorded. The presence or absence of 17 microscopic features was noted. Concordance between pre-biopsy and histopathologic diagnosis was noted in 57.28% of cases, suggesting that the diagnosis is often not suspected clinically. Among the histopathologic features studied, a compact stratum corneum (either uniform or forming a layer beneath a basket weave stratum corneum), parakeratosis, mild spongiosis and neutrophils in the stratum corneum and within the blood vessels were the most frequent features noted. This study suggests histopathologic clues that should prompt the pathologist to order a PAS stain, especially when diagnosis is not suspected clinically. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acral peeling skin syndrome: report of two cases.

PubMed

García, Elena García; Carreño, Rosario Granados; Martínez González, Miguel A; Reyes, José Jiménez

2005-01-01

Peeling skin syndrome is a rare dermatosis characterized by spontaneous and painless peeling of the skin. The authors report two patients with history of spontaneous, asymptomatic, and noninflammatory peeling skin of the acral surfaces after soaking in water. On light microscopy, blisters were located in the mid layers of the stratum corneum, above the granular layer. Ultrastructural examination revealed increased intercellular lipids and abnormal, "moth-eaten," keratohyalin granules, but the authors were unable to determine whether the separation initiated within the horny cells or between adjacent cells. These patients represented a localized variant of peeling skin syndrome.

Development and evaluation of nanostructured lipid carrier-based hydrogel for topical delivery of 5-fluorouracil

PubMed Central

Rajinikanth, Paruvathanahalli Siddalingam; Chellian, Jestin

2016-01-01

The aim of this study was to develop a nanostructured lipid carrier (NLC)-based hydrogel and study its potential for the topical delivery of 5-fluorouracil (5-FU). Precirol® ATO 5 (glyceryl palmitostearate) and Labrasol® were selected as the solid and liquid lipid phases, respectively. Poloxamer 188 and Solutol® HS15 (polyoxyl-15-hydroxystearate) were selected as surfactants. The developed lipid formulations were dispersed in 1% Carbopol® 934 (poly[acrylic acid]) gel medium in order to maintain the topical application consistency. The average size, zeta potential, and polydispersity index for the 5-FU-NLC were found to be 208.32±8.21 nm, −21.82±0.40 mV, and 0.352±0.060, respectively. Transmission electron microscopy study revealed that 5-FU-NLC was <200 nm in size, with a spherical shape. In vitro drug permeation studies showed a release pattern with initial burst followed by sustained release, and the rate of 5-FU permeation was significantly improved for 5-FU-NLC gel (10.27±1.82 μg/cm2/h) as compared with plain 5-FU gel (2.85±1.12 μg/cm2/h). Further, skin retention studies showed a significant retention of 5-FU from the NLC gel (91.256±4.56 μg/cm2) as compared with that from the 5-FU plain gel (12.23±3.86 μg/cm2) in the rat skin. Skin irritation was also significantly reduced with 5-FU-NLC gel as compared with 5-FU plain gel. These results show that the prepared 5-FU-loaded NLC has high potential to improve the penetration of 5-FU through the stratum corneum, with enormous retention and with minimal skin irritation, which is the prerequisite for topically applied formulations. PMID:27785014

Relationship between biochemical factors and skin symptoms in chronic venous disease.

PubMed

Takai, Yasushi; Hiramoto, Keiichi; Nishimura, Yoshiyuki; Ooi, Kazuya

2017-05-01

Chronic venous disease (CVD) is a common venous disease of the lower extremities and patients often develop symptoms of itching and skin roughness. An easy to use and objective skin examination was recently developed that allows measurement of the level of stratum corneum content and transepidermal water loss (TEWL), which can indicate the status of the barrier function of the stratum corneum. Previous studies demonstrated that histamine production from mast cells, and tryptase and matrix metalloprotease-9 levels were associated with skin inflammation. This study aimed to clarify the relationship between dry skin and inflammatory mediators that mediate the skin symptoms of CVD subjects. The study enrolled 27 subjects with CVD and a control group consisting of 9 volunteers. The itching onset frequency was higher in women (70.4%) compared with men (50.0%). To analyze the mechanisms involved in itching we measured blood inflammatory mediators pre- and post-sclerotherapy. There was a significant decrease in Substance P, histamine, IgE, and tryptase levels post-sclerotherapy compared with those at pre-sclerotherapy. These levels were associated with the severity of itching. In addition, compared with the control subjects, there was a significant increase in the stratum corneum water content and a decrease in the TEWL in the 27 patients with CVD. This was associated with a decrease in the itching symptoms. Our findings indicate that sclerotherapy decreased levels of inflammatory mediators, increased stratum corneum water content and decreased TEWL, which coincided with reduced itching in CVD patients, indicating they might be therapeutic targets.

Fatty Aldehyde and Fatty Alcohol Metabolism: Review and Importance for Epidermal Structure and Function

PubMed Central

Rizzo, William B.

2014-01-01

Normal fatty aldehyde and alcohol metabolism is essential for epidermal differentiation and function. Long-chain aldehydes are produced by catabolism of several lipids including fatty alcohols, sphingolipids, ether glycerolipids, isoprenoid alcohols and certain aliphatic lipids that undergo α- or ω-oxidation. The fatty aldehyde generated by these pathways is chiefly metabolized to fatty acid by fatty aldehyde dehydrogenase (FALDH, alternately known as ALDH3A2), which also functions to oxidize fatty alcohols as a component of the fatty alcohol:NAD oxidoreductase (FAO) enzyme complex. Genetic deficiency of FALDH/FAO in patients with Sjögren-Larsson syndrome (SLS) results in accumulation of fatty aldehydes, fatty alcohols and related lipids (ether glycerolipids, wax esters) in cultured keratinocytes. These biochemical changes are associated with abnormalities in formation of lamellar bodies in the stratum granulosum and impaired delivery of their precursor membranes to the stratum corneum (SC). The defective extracellular SC membranes are responsible for a leaky epidermal water barrier and ichthyosis. Although lamellar bodies appear to be the pathogenic target for abnormal fatty aldehyde/alcohol metabolism in SLS, the precise biochemical mechanisms are yet to be elucidated. Nevertheless, studies in SLS highlight the critical importance of FALDH and normal fatty aldehyde/alcohol metabolism for epidermal function. PMID:24036493

Using FLIM in the study of permeability barrier function of aged and young skin

NASA Astrophysics Data System (ADS)

Xu, P.; Choi, E. H.; Man, M. Q.; Crumrine, D.; Mauro, T.; Elias, P.

2006-02-01

Aged skin commonly is afflicted by inflammatory skin diseases or xerosis/eczema that can be triggered or exacerbated by impaired epidermal permeability barrier homeostasis. It has been previously described a permeability barrier defect in humans of advanced age (> 75 years), which in a murine analog >18 mos, could be attributed to reduced lipid synthesis synthesis. However, the functional abnormality in moderately aged mice is due not to decreased lipid synthesis, but rather to a specific defect in stratum corneum (SC) acidification causing impaired lipid processing processing. Endogenous Na +/H + antiporter (NHE1) level was found declined in moderately aged mouse epidermis. This acidification defect leads to perturbed permeability barrier homeostasis through more than one pathways, we addressed suboptimal activation of the essential, lipid-processing enzyme, β-glucocerebrosidase (BGC) is linked to elevated SC pH. Finally, the importance of the epidermis acidity is shown by the normalization of barrier function after exogenous acidification of moderately aged skin.

Using low-frequency ultrasound to improve the optical clearing of porcine skin

NASA Astrophysics Data System (ADS)

Zhong, Huiqing; Guo, Zhouyi; Wei, Huajiang; Zhang, Zude; Zeng, Changchun; Zhai, Juan; He, Yonghong

2008-12-01

The glycerol used as an enhancer for tissue optical clearing technique has been researched. However, using it and a physical way of ultrasound enhance optical clearing of tissue reported a few. We researched that the ultrasound whether can improve the optical clearing of dealt with 80% glycerol tissue. The fresh porcine skins divided into four groups. The first group was not dealt with by ultrasound and 80% glycerol, the second group was dealt with by only ultrasound, the third group was dealt with by 80% glycerol and no by ultrasound, and the fourth group was dealt with by both 80% glycerol and ultrasound. And we measured changes in optical scattering of the porcine skins under treatment with OCT. From the OCT images show that the fourth group changed very faster than the other's during the 0~15 min. And it can be clearly seen that there is a significant improvement in the light penetration depth and imaging contrast in a shorter time. It is possible that the low-frequency ultrasound can make disordering of the stratum corneum lipids of the porcine skin (because the cavitation has happened), and improve the speed of 80% glycerol through the stratum corneum of skin. These results proved that using 80% glycerol with the ultrasound can better improve the optical clearing of tissue.

Effects of various vehicles on skin hydration in vivo.

PubMed

Wiedersberg, S; Leopold, C S; Guy, R H

2009-01-01

The stratum corneum, the outermost layer of the skin, regulates the passive loss of water to the environment. Furthermore, it is well accepted that drug penetration is influenced by skin hydration, which may be manipulated by the application of moisturizing or oleaginous vehicles. Measurements of transepidermal water loss (TEWL), and of skin hydration using a corneometer, were used to assess the effect of different vehicles on stratum corneum barrier function in vivo in human volunteers. A microemulsion significantly increased skin hydration relative to a reference vehicle based on medium chain triglycerides; in contrast, Transcutol(R) lowered skin hydration. TEWL measurements confirmed these observations. Copyright 2009 S. Karger AG, Basel.

Metabolic approaches to enhance transdermal drug delivery. 1. Effect of lipid synthesis inhibitors.

PubMed

Tsai, J C; Guy, R H; Thornfeldt, C R; Gao, W N; Feingold, K R; Elias, P M

1996-06-01

The intercellular domains of the stratum corneum, which contain a mixture of cholesterol, free fatty acids, and ceramides, mediate both the epidermal permeability barrier and the transdermal delivery of both lipophilic and hydrophilic molecules. Prior studies have shown that each of the three key lipid classes is required for normal barrier function. For example, selective inhibition of either cholesterol, fatty acid, or ceramide synthesis in the epidermis delays barrier recovery rates after barrier perturbation of hairless mouse skin in vivo. In this study, we investigated the potential of certain inhibitors of lipid synthesis to enhance the transdermal delivery of lidocaine or caffeine as a result of their capacity to perturb barrier homeostasis. After acetone disruption of the barrier, the extent of lidocaine delivery and the degree of altered barrier function paralleled each other. Moreover, the further alteration in barrier function produced by either the fatty acid synthesis inhibitor 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA), the cholesterol synthesis inhibitor fluvastatin (FLU), or cholesterol sulfate (CS) resulted in a further increase in lidocaine absorption. Furthermore, coapplications of TOFA and CS together caused an additive increase in lidocaine uptake. Finally, a comparable increase in drug delivery occurred when the barrier was disrupted initially with DMSO instead of acetone; coapplications of TOFA and FLU together again delayed barrier recovery and increased drug delivery by about 8-fold vs delivery from a standard enhancing vehicle. Whereas these metabolic inhibitors also variably increased the octanol/water partitioning of the drugs studied (perhaps via complexion or pH alterations), physicochemical effects of the inhibitors alone did not alter drug uptake in intact skin; i.e., passive mechanisms alone cannot account for the net increase in drug delivery. Our results show that modulations of epidermal lipid biosynthesis, following

In vivo skin moisturizing measurement by high-resolution 3 Tesla magnetic resonance imaging.

PubMed

Mesrar, J; Ognard, J; Garetier, M; Chechin, D; Misery, L; Ben Salem, D

2017-08-01

Magnetic resonance imaging (MRI) is rarely used for the exploration of skin, even if studies have validated both feasibility of skin MRI and its interest for anatomical, physiological, and biochemical study of the skin. The purpose of this study is to explore moisturizing of the different skin layers using 3-T scan. An MRI of the heel's skin was performed using a 23 mm coil diameter on a 3T scan with a FFE (Fast Field Echo) 3D T1-weighted sequence and a TSE (Turbo Spin Echo) calculation T2-weighted sequence (pixels size of respectively 60 and 70 μm). This study was conducted on 35 healthy volunteers, who were scanned before applying moisturizer topic and 1 h after applying it. Region of interest in the stratum corneum, the epidermis and the dermis were generated on the T2 mapping. The thickness of each layer was measured. The T1 sequence allowed accurate cross-examination repositioning to ensure the comparability of the measurements. Among the 35 cases, two were excluded from the analysis because of movement artifacts. Measurements before and after moisturizer topic application displayed a T2 increase of 48.94% (P < 0.0001) in the stratum corneum and of 5.45% (P < 0.0001) in the epidermis yet without significant difference in the dermis. There was no significant link between the thickness of the stratum corneum and the T2 increase. However, there was a strong correlation between the thickness of the stratum corneum and the thickness of the epidermis (P < 0.001; rhô=0.72). High-resolution MRI allows fine exploration of anatomical and physiological properties of the skin and can further be used to extend the studies of skin hydration. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Emulsion-Based Intradermal Delivery of Melittin in Rats.

PubMed

Han, Sang Mi; Kim, Se Gun; Pak, Sok Cheon

2017-05-19

Bee venom (BV) has long been used as a traditional medicine. The aim of the present study was to formulate a BV emulsion with good rheological properties for dermal application and investigate the effect of formulation on the permeation of melittin through dermatomed rat skin. A formulated emulsion containing 1% ( w / v ) BV was prepared. The emulsion was compared with distilled water (DW) and 25% ( w / v ) N -methyl-2-pyrrolidone (NMP) in DW. Permeation of melittin from aqueous solution through the dermatomed murine skin was evaluated using the Franz diffusion cells. Samples of receptor cells withdrawn at pre-determined time intervals were measured for melittin amount. After the permeation study, the same skin was used for melittin extraction. In addition, a known amount of melittin (5 μg/mL) was added to stratum corneum, epidermis, and dermis of the rat skin, and the amount of melittin was measured at pre-determined time points. The measurement of melittin from all samples was done with HPLC-MS/MS. No melittin was detected in the receptor phase at all time points in emulsion, DW, or NMP groups. When the amount of melittin was further analyzed in stratum corneum, epidermis, and dermis from the permeation study, melittin was still not detected. In an additional experiment, the amount of melittin added to all skin matrices was corrected against the amount of melittin recovered. While the total amount of melittin was retained in the stratum corneum, less than 10% of melittin remained in epidermis and dermis within 15 and 30 min, respectively. Skin microporation with BV emulsion facilitates the penetration of melittin across the stratum corneum into epidermis and dermis, where emulsified melittin could have been metabolized by locally-occurring enzymes.

Development of a rate model to investigate contributions of anatomic and physiologic determinants of in vivo skin permeation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fleischer, N.M.

The skin is a heterogeneous, bi-directional impediment to chemical flux, in which the stratum corneum is a major, though not the sole, rate-limiting barrier layer to permeation. Systemic toxicity following dermal exposure to environmental chemicals and use of skin as a portal for systemic administration of drugs have led to extensive investigations of the inward flux of xenobiotics applied to the outer surface of skin. Those investigations mainly utilized in vitro experimental systems that were limited by the absence of normal physiologic functions. The objective of the present research was to investigate an in vivo skin permeation model system thatmore » was sensitive to perturbations of skin capillary physiology and stratum corneum. A [open quotes]fuzzy[close quotes] rat model system was devised that employed outward cutaneous migration of a systemically administered permeation probe, isoflurane. Specially devised, transdermal vapor collection devices were used to capture the outward flux of isoflurane through the skin. Isoflurane flux measurements, coupled with blood isoflurane concentrations, were used to calculate cutaneous permeability coefficients (K[sub p]) of isolflurane, as an index of permeation, under various conditions of normal or perturbed cutaneous physiologic states. Physiologic perturbations were performed to test the sensitivity of the model system to detect effects of minoxidil-mediated vasodilation, phenylephrine-mediated vasoconstriction, and leukotriene D[sub 4]-mediated increased capillary permeability on the outward flux of isoflurane. Tape stripping and topical ether-ethanol application produced either physical removal or chemical disruption of the stratum corneum, respectively. Minoxidil, leukotriene D[sub 4], tape stripping of stratum corneum, and topical ether-ethanol experiments produced statistically significant increases (52 to 193%) in the K[sub p's], while phenylephrine had no significant effect on isoflurane permeation.« less

Infrared spectroscopic measurement of skin hydration and sebum levels and comparison to corneometer and sebumeter

NASA Astrophysics Data System (ADS)

Ezerskaia, Anna; Pereira, S. F.; Urbach, H. P.; Varghese, Babu

2016-05-01

Skin health characterized by a system of water and lipids in Stratum Corneum provide protection from harmful external elements and prevent trans-epidermal water loss. Skin hydration (moisture) and sebum (skin surface lipids) are considered to be important factors in skin health; a right balance between these components is an indication of skin health and plays a central role in protecting and preserving skin integrity. In this manuscript we present an infrared spectroscopic method for simultaneous and quantitative measurement of skin hydration and sebum levels utilizing differential detection with three wavelengths 1720, 1750, and 1770 nm, corresponding to the lipid vibrational bands that lie "in between" the prominent water absorption bands. The skin sebum and hydration values on the forehead under natural conditions and its variations to external stimuli were measured using our experimental set-up. The experimental results obtained with the optical set-up show good correlation with the results obtained with the commercially available instruments Corneometer and Sebumeter.

Evaluation of a human bio-engineered skin equivalent for drug permeation studies.

PubMed

Asbill, C; Kim, N; El-Kattan, A; Creek, K; Wertz, P; Michniak, B

2000-09-01

To test the barrier function of a bio-engineered human skin (BHS) using three model drugs (caffeine, hydrocortisone, and tamoxifen) in vitro. To investigate the lipid composition and microscopic structure of the BHS. The human skin substitute was composed of both epidermal and dermal layers, the latter having a bovine collagen matrix. The permeability of the BHS to three model drugs was compared to that obtained in other percutaneous testing models (human cadaver skin, hairless mouse skin, and EpiDerm). Lipid analysis of the BHS was performed by high performance thin layered chromatography. Histological evaluation of the BHS was performed using routine H&E staining. The BHS mimicked human skin in terms of lipid composition, gross ultrastructure, and the formation of a stratum corneum. However, the permeability of the BHS to caffeine, hydrocortisone, and tamoxifen was 3-4 fold higher than that of human cadaver skin. In summary, the results indicate that the BHS may be an acceptable in vitro model for drug permeability testing.

Topical delivery of liposomally encapsulated interferon evaluated in a cutaneous herpes guinea pig model.

PubMed Central

Weiner, N; Williams, N; Birch, G; Ramachandran, C; Shipman, C; Flynn, G

1989-01-01

The topical delivery of liposomally encapsulated interferon was evaluated in the cutaneous herpes simplex virus guinea pig model. Application of liposomally entrapped interferon caused a reduction of lesion scores, whereas application of interferon formulated as a solution or as an emulsion was ineffective. The method of liposomal preparation rather than the lipid composition of the bilayers appeared to be the most important factor for reducing lesion scores. Only liposomes prepared by the dehydration-rehydration method were effective. This finding implied that the dehydration and subsequent rehydration of the liposomes facilitate partitioning of the interferon into liposomal bilayers, where the drug is positioned for transfer into the lipid compartment of the stratum corneum. Liposomes do not appear to function as permeation enhancers but seem to provide the needed physicochemical environment for transfer of interferon into the skin. PMID:2802550

Chemical peeling by SA-PEG remodels photo-damaged skin: suppressing p53 expression and normalizing keratinocyte differentiation.

PubMed

Dainichi, Teruki; Amano, Satoshi; Matsunaga, Yukiko; Iriyama, Shunsuke; Hirao, Tetsuji; Hariya, Takeshi; Hibino, Toshihiko; Katagiri, Chika; Takahashi, Motoji; Ueda, Setsuko; Furue, Masutaka

2006-02-01

Chemical peeling with salicylic acid in polyethylene glycol vehicle (SA-PEG), which specifically acts on the stratum corneum, suppresses the development of skin tumors in UVB-irradiated hairless mice. To elucidate the mechanism through which chemical peeling with SA-PEG suppresses skin tumor development, the effects of chemical peeling on photodamaged keratinocytes and cornified envelopes (CEs) were evaluated in vivo. Among UVB-irradiated hairless mice, the structural atypia and expression of p53 protein in keratinocytes induced by UVB irradiation were intensely suppressed in the SA-PEG-treated mice 28 days after the start of weekly SA-PEG treatments when compared to that in the control UVB-irradiated mice. Incomplete expression of filaggrin and loricrin in keratinocytes from the control mice was also improved in keratinocytes from the SA-PEG-treated mice. In photo-exposed human facial skin, immature CEs were replaced with mature CEs 4 weeks after treatment with SA-PEG. Restoration of photodamaged stratum corneum by treatment with SA-PEG, which may affect remodeling of the structural environment of the keratinocytes, involved the normalization of keratinocyte differentiation and suppression of skin tumor development. These results suggest that the stratum corneum plays a protective role against carcinogenesis, and provide a novel strategy for the prevention of photo-induced skin tumors.

Topical bioavailability of diclofenac from locally-acting, dermatological formulations.

PubMed

Cordery, S F; Pensado, A; Chiu, W S; Shehab, M Z; Bunge, A L; Delgado-Charro, M B; Guy, R H

2017-08-30

Assessment of the bioavailability of topically applied drugs designed to act within or beneath the skin is a challenging objective. A number of different, but potentially complementary, techniques are under evaluation. The objective of this work was to evaluate in vitro skin penetration and stratum corneum tape-stripping in vivo as tools with which to measure topical diclofenac bioavailability from three approved and commercialized products (two gels and one solution). Drug uptake into, and its subsequent clearance from, the stratum corneum of human volunteers was used to estimate the input rate of diclofenac into the viable skin layers. This flux was compared to that measured across excised porcine skin in conventional diffusion cells. Both techniques clearly demonstrated (a) the superiority in terms of drug delivery from the solution, and (b) that the two gels performed similarly. There was qualitative and, importantly, quantitative agreement between the in vitro and in vivo measurements of drug flux into and beyond the viable skin. Evidence is therefore presented to support an in vivo - in vitro correlation between methods to assess topical drug bioavailability. The potential value of the stratum corneum tape-stripping technique to quantify drug delivery into (epi)dermal and subcutaneous tissue beneath the barrier is demonstrated. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of Rice Koji Extract Components that Increase β-Glucocerebrosidase Levels in Human Epidermal Keratinocytes.

PubMed

Maeda, Kazuhisa; Ogino, Yuuka; Nakamura, Ayano; Nakata, Keiji; Kitagawa, Manabu; Ito, Seiki

2018-06-18

Rice miso contains many ingredients derived from rice koji and has been a valuable source of nutrition since ancient times. We found that the consumption of rice miso led to improvements in the moisture content of cheek stratum corneum, skin viscoelasticity, and skin texture. Further, rice miso extract was found to increase the mRNA expression and activity of β-glucocerebrosidase (β-GCase), an enzyme involved in ceramide synthesis in the stratum corneum, in cultures. In this study, we identified the lipid-derived components of rice koji that increase the β-GCase activity in cultured human epidermal keratinocytes. The methanol fraction of rice koji extract induced an increase in the mRNA expression and activity of β-GCase in keratinocytes. The active fraction of rice koji was found to contain phosphatidic acid (PA) and lysophosphatidic acid (LPA). The total PA concentration in rice koji was 973.9 ng/mg dry weight, which was 17.5 times higher than that in steamed rice. Among the molecular species, PA_18:2/18:2 was the most frequently found. The total LPA concentration in rice koji was 29.6 ng/mg dry weight, and 2-LPA_18:2 was the most frequently found LPA. Since PA and LPA increase the mRNA expression and activity of β-GCase in keratinocytes, they are thought to be the active ingredients in rice koji that increase the β-GCase levels in human epidermal keratinocytes.

The Effects of Judgment-Based Stratum Classifications on the Efficiency of Stratum Scored CATs.

ERIC Educational Resources Information Center

Finney, Sara J.; Smith, Russell W.; Wise, Steven L.

Two operational item pools were used to investigate the performance of stratum computerized adaptive tests (CATs) when items were assigned to strata based on empirical estimates of item difficulty or human judgments of item difficulty. Items from the first data set consisted of 54 5-option multiple choice items from a form of the ACT mathematics…

Simulation study of the structure and phase behavior of ceramide bilayers and the role of lipid head group chemistry

PubMed Central

Guo, Shan; Moore, Timothy C.; Iacovella, Christopher R.; Strickland, L. Anderson; McCabe, Clare

2014-01-01

Ceramides are known to be a key component of the stratum corneum, the outermost protective layer of the skin that controls barrier function. In this work, molecular dynamics simulations are used to examine the behavior of ceramide bilayers, focusing on non-hydroxy sphingosine (NS) and non-hydroxy phytosphingosine (NP) ceramides. Here, we propose a modified version of the CHARMM force field for ceramide simulation, which is directly compared to the more commonly used GROMOS-based force field of Berger (Biophys. J. 1997, 72); while both force fields are shown to closely match experiment from a structural standpoint at the physiological temperature of skin, the modified CHARMM force field is better able to capture the thermotropic phase transitions observed in experiment. The role of ceramide chemistry and its impact on structural ordering is examined by comparing ceramide NS to NP, using the validated CHARMM-based force field. These simulations demonstrate that changing from ceramide NS to NP results in changes to the orientation of the OH groups in the lipid headgroups. The arrangement of OH groups perpendicular to the bilayer normal for ceramide NP, verse parallel for NS, results in the formation of a distinct hydrogen bonding network, that is ultimately responsible for shifting the gel-to-liquid phase transition to higher temperature, in direct agreement with experiment. PMID:24501589

Climate change and cutaneous water loss of birds.

PubMed

Williams, Joseph B; Muñoz-Garcia, Agustí; Champagne, Alex

2012-04-01

There is a crucial need to understand how physiological systems of animals will respond to increases in global air temperature. Water conservation may become more important for some species of birds, especially those living in deserts. Lipids of the stratum corneum (SC), the outer layer of the epidermis, create the barrier to water vapor diffusion, and thus control cutaneous water loss (CWL). An appreciation of the ability of birds to change CWL by altering lipids of the skin will be important to predict responses of birds to global warming. The interactions of these lipids are fundamental to the modulation of water loss through skin. Cerebrosides, with their hexose sugar moiety, are a key component of the SC in birds, but how these lipids interact with other lipids of the SC, or how they form hydrogen bonds with water molecules, to form a barrier to water vapor diffusion remains unknown. An understanding of how cerebrosides interact with other lipids of the SC, and of how the hydroxyl groups of cerebrosides interact with water molecules, may be a key to elucidating the control of CWL by the SC.

The effects of aromatherapy on pruritus in patients undergoing hemodialysis.

PubMed

Ro, You-Ja; Ha, Hyae-Chung; Kim, Chun-Gill; Yeom, Hye-A

2002-08-01

This study was designed to investigate the effects of aromatherapy on pruritus in patients with chronic renal failure undergoing hemodialysis. The participants were 29 adult patients living in Seoul, Korea. Thirteen patients were assigned to the experimental group and received the aromatherapy massage on the arm 3 times a week for 4 weeks. Pruritus score, skin pH, stratum corneum hydration, and pruritus-related biochemical markers were measured before and after the treatment. The results showed that pruritus score was significantly decreased after aromatherapy. Skin pH showed no significant changes in either group while stratum corneum hydration increased significantly in the experimental group after aromatherapy. The results support the use aromatherapy as a useful and effective method of managing pruritus in patients undergoing hemodialysis.

Cyanoacrylate Skin Surface Stripping and the 3S-Biokit Advent in Tropical Dermatology: A Look from Liège

PubMed Central

Piérard, Gérald E.; Piérard-Franchimont, Claudine; Paquet, Philippe; Hermanns-Lê, Trinh; Delvenne, Philippe

2014-01-01

In the dermatopathology field, some simple available laboratory tests require minimum equipment for establishing a diagnosis. Among them, the cyanoacrylate skin surface stripping (CSSS), formerly named skin surface biopsy or follicular biopsy, represents a convenient low cost procedure. It is a minimally invasive method collecting a continuous sheet of stratum corneum and horny follicular casts. In the vast majority of cases, it is painless and is unassociated with adverse events. CSSS can be performed in subjects of any age. The method has a number of applications in diagnostic dermatopathology and cosmetology, as well as in experimental dermatology settings. A series of derived analytic procedures include xerosis grading, comedometry, corneofungimetry, corneodynamics of stratum corneum renewal, corneomelametry, corneosurfametry, and corneoxenometry. PMID:25177726

Effects of microgravity on epidermal development in the rat

NASA Technical Reports Server (NTRS)

Hoath, Steven B.

1995-01-01

The overall goal of this project was to investigate the effects of prolonged weightlessness on the development of the skin in the fetal and newborn rat. Specifically, we used the NASA microgravitational rat model to test the following hypotheses: (1) Exposure of the pregnant rat to microscopy during late gestation will diminish the transport of calcium across the placenta from the mother to the fetus leading to decreases in total epidermal and dermal calcium content; (2) Microgravity will lead to slowing of body growth and diminish the rate of formation of the outermost layer of the epidermis and the stratum corneum; and (3) Microgravity will lead to formation of a stratum corneum with decreased DC electrical resistance and increased permeability to tritiated water.

Sensitivity of FIA Volume Estimates to Changes in Stratum Weights and Number of Strata

Treesearch

James A. Westfall; Michael Hoppus

2005-01-01

In the Northeast region, the USDA Forest Service Forest Inventory and Analysis (FIA) program utilizes stratified sampling techniques to improve the precision of population estimates. Recently, interpretation of aerial photographs was replaced with classified remotely sensed imagery to determine stratum weights and plot stratum assignments. However, stratum weights...

Stratum variance estimation for sample allocation in crop surveys. [Great Plains Corridor

NASA Technical Reports Server (NTRS)

Perry, C. R., Jr.; Chhikara, R. S. (Principal Investigator)

1980-01-01

The problem of determining stratum variances needed in achieving an optimum sample allocation for crop surveys by remote sensing is investigated by considering an approach based on the concept of stratum variance as a function of the sampling unit size. A methodology using the existing and easily available information of historical crop statistics is developed for obtaining initial estimates of tratum variances. The procedure is applied to estimate stratum variances for wheat in the U.S. Great Plains and is evaluated based on the numerical results thus obtained. It is shown that the proposed technique is viable and performs satisfactorily, with the use of a conservative value for the field size and the crop statistics from the small political subdivision level, when the estimated stratum variances were compared to those obtained using the LANDSAT data.

An evaluation of the skin stripping of wound dressing adhesives.

PubMed

Waring, M; Bielfeldt, S; Mätzold, K; Wilhelm, K P; Butcher, M

2011-09-01

This study looks at six different modern wound dressings to investigate how likely they are to cause skin stripping and impairment of the skin's barrier function. Healthy volunteers had each dressing applied, removed and reapplied to the skin on their back over the study period of 15 days. Skin barrier function was investigated using the amount of transepidermal water loss (TEWL) and then related to the amount of skin stripping, investigated by measuring stained skin removal, the thickness of the stratum corneum after treatment, and the amount of skin attached to the removed dressings. General signs of trauma, such as skin dryness and erythema, were investigated by subjective and objective parameters. TEWL values measured on the untreated test area, as well as after application of Urgotul Trio, remained relatively unchanged and Mepilex Border decreased slightly (?1g/m2/h), while all other dressings displayed an increased in TEWL: Allevyn Adhesive (5g/m2/h), Versiva XC (14g/m2/h), Comfeel Plus (22g/m2/h) and Biatain (28g/m2/h). By the end of the study, only the untreated area (mean 43% dye remaining), Mepilex Border (76%) and Urgotul Trio (34%) areas had visible dye remaining. It is interesting to note that the untreated site had a colour change, suggesting loss of stratum corneum, due to the shedding of skin cells from the surface. The increase in total skin colour for Comfeel Plus and Biatain after day 8 might be assigned to an increased redness due to erythema. All the dressings showed evidence of stratum corneum attached to the adhesive, except Mepilex Border, which appeared to be free of any attached stratum corneum. Overall the best performance in terms of skin protection and failure to cause skin trauma was found to be for Mepilex Border. This project was funded by a grant from Mölnlycke Healthcare Ltd.

Improving diaper design to address incontinence associated dermatitis

PubMed Central

2010-01-01

Background Incontinence associated dermatitis (IAD) is an inflammatory skin disease mainly triggered by prolonged skin contact with urine, feces but also liberal detergent use when cleansing the skin. To minimize the epidermal barrier challenge we optimized the design of adult incontinence briefs. In the fluid absorption area we interposed a special type of acidic, curled-type of cellulose between the top sheet in contact with the skin and the absorption core beneath containing the polyacrylate superabsorber. The intention was to minimize disturbance of the already weak acid mantle of aged skin. We also employed air-permeable side panels to minimize skin occlusion and swelling of the stratum corneum. Methods The surface pH of diapers was measured after repeated wetting with a urine substitute fluid at the level of the top sheet. Occlusive effects and hydration of the stratum corneum were measured after a 4 hour application of different side panel materials by corneometry on human volunteers. Finally, we evaluated skin symptoms in 12 patients with preexisting IAD for 21 days following the institutional switch to the optimized diaper design. Local skin care protocols remained in place unchanged. Results The improved design created a surface pH of 4.6 which was stable even after repeated wetting throughout a 5 hour period. The "standard design" briefs had values of 7.1, which is alkaline compared to the acidic surface of normal skin. Side panels made from non-woven material with an air-permeability of more than 1200 l/m2/s avoided excessive hydration of the stratum corneum when compared to the commonly employed air-impermeable plastic films. Resolution of pre-existing IAD skin lesions was noted in 8 out of 12 patients after the switch to the optimized brief design. Conclusions An improved design of adult-type briefs can create an acidic pH on the surface and breathable side panels avoid over-hydration of the stratum corneum and occlusion. This may support the

Mechanical properties of a Gelidium corneum edible film containing catechin and its application in sausages.

PubMed

Ku, K-J; Hong, Y-H; Song, K B

2008-04-01

We prepared an edible Gelidium corneum (GC) film containing catechin and examined the microbial growth and quality change during storage of sausages packaged with the film. Incorporation of catechin in the film improved film tensile strength and water vapor permeability. The film's antimicrobial activity against Eschericha coli O157:H7 increased with increasing catechin concentrations and resulted in a decrease in the populations of the bacteria by 1.93 log CFU/g at 150 mg of catechin. For the sausage samples inoculated with E. coli O157:H7 and Listeria monocytogenes, the samples packed with the GC film showed a decrease in populations of E. coli O157:H7 and L. monocytogenes by 1.81 and 1.44 log CFU/g, respectively, compared to the control after 5 d of storage. In addition, the sausage samples packed with the GC film had lower degrees of lipid oxidation. The results suggest that sausages can be packed with GC film to extend shelf life.

Sarcoptic mange in free-ranging raccoon dogs (Nyctereutes procyonoides) in Japan.

PubMed

Ninomiya, Hiroyoshi; Ogata, Munetsugu

2005-06-01

Sarcoptes scabiei infestation was diagnosed in three freshly dead free-ranging raccoon dogs (Nyctereutes procyonoides) in Kanagawa Prefecture, Japan. The dogs presented with an alopecic pruritic skin disease, with signs of alopecia on the ears, muzzle, around the eyes, elbow, thigh and the neck, and hyperpigmented and crusted skin lesions, which had a severe malodour. Skin scrapings revealed the presence of the mite Sarcoptes scabiei. Histopathology of lesions demonstrated marked acanthosis, hyperkeratosis, parakeratosis and fungal elements, which were subsequently identified as Acremonium sp., Alternaria sp. and an unknown fungus. Mite segments were located mainly in the stratum corneum and also in the stratum granulosum. Tunnels could be observed in the hyperkeratotic stratum corneum. Scanning electron microscopy (SEM) revealed the tortoise-like Sarcoptes scabiei with four long bristles, suckers and blade-like claws on legs 1 and 2, cuticular spines, prominent body striations and a terminal anus. SEM also revealed an adult female mite digging a tunnel with the head wedged into the very end of the closed burrow. Tunnels filled with eggshells, corneocyte debris and faecal pellets were also observed.

Lysine-based surfactants as chemical permeation enhancers for dermal delivery of local anesthetics.

PubMed

Teixeira, Raquel S; Cova, Tânia F G G; Silva, Sérgio M C; Oliveira, Rita; Araújo, Maria J; Marques, Eduardo F; Pais, Alberto A C C; Veiga, Francisco J B

2014-10-20

The aim of this study is to investigate the efficacy of new, biocompatible, lysine-based surfactants as chemical permeation enhancers for two different local anesthetics, tetracaine and ropivacaine hydrochloride, topically administered. Results show that this class of surfactants strongly influences permeation, especially in the case of the hydrophilic and ionized drug, ropivacaine hydrochloride, that is not easily administered through the stratum corneum. It is also seen that the selected permeation enhancers do not have significant deleterious effects on the skin structure. A cytotoxicity profile for each compound was established from cytotoxicity studies. Molecular dynamics simulation results provided a rationale for the experimental observations, introducing a mechanistic view of the action of the surfactants molecules upon lipid membranes. Copyright © 2014. Published by Elsevier B.V.

Effects of ammonia and hydrogen sulfide on physical and biochemical properties of the claw horn of Holstein cows

PubMed Central

Higuchi, Hidetoshi; Kurumado, Hisatoshi; Mori, Maya; Degawa, Aiko; Fujisawa, Hideyo; Kuwano, Atsutoshi; Nagahata, Hajime

2009-01-01

The effects of ammonia and hydrogen sulfide on the physical and biochemical properties of the claw horn of Holstein cows were evaluated. Significant (P < 0.05, 0.01) decreases in hardness and elasticity were found in claw horns soaked in ammonia (NH3) and hydrogen sulfide (H2S) solutions compared with those that were soaked in water for 12, 24, and 48 h. Water absorption rate, as a indicator of permeability barrier function, increased significantly (P < 0.05) over time during the soaking period and was found to be dependent on the concentrations of NH3 and H2S in the solutions. The contents of ceramide, the main lipid component for the permeability barrier system of the stratum corneum, were significantly decreased in claw horns soaked in NH3 and H2S solutions compared with the values before soaking. Quantities of eluted protein released from claw horns treated with NH3 and H2S solutions were approximately 20 times and 30 to 40 times greater than those released from claw horns treated with water alone. Interestingly, the quantities of cytokeratin 10, the main cytoskeletal protein of the stratum corneum, eluted from claw horns treated with NH3 and H2S solutions were markedly greater than the quantity released from horns soaked in water. Our results suggest that abnormal changes in the physical property of claw horn caused by NH3 and H2S treatment are due to disruption of the biochemical property of the claw horn induced by these chemical agents derived from slurry. PMID:19337390

A cleanser based on sodium laureth carboxylate and alkyl carboxylates washes facial sebum well but does not induce dry skin.

PubMed

Yokoi, Aya; Endo, Koji; Ozawa, Toshiaki; Miyaki, Masahiro; Matsuo, Keiko; Nozawa, Kazumi; Manabe, Motomu; Takagi, Yutaka

2014-12-01

Because excess sebum and/or metabolites of sebum induce skin problems, cleansers that can remove those kinds of sebum are sought after. However, many people, especially who have little facial sebum, are afraid to wash off sebum well because that may induce dry skin. This concern may be caused by the result that cleansers with a high cleansing ability tend to decrease not only facial sebum but also natural moisturizing factors and intercellular lipids that are essential for cutaneous function. Recently, we have developed a new cleanser based on sodium laureth carboxylate and alkyl carboxylates (AEC/soap) that cleans sebum well without penetrating the stratum corneum. This trial was aim to clarify the effects of sebum removal by AEC/soap-based cleanser on the induction of dry skin. We designed a controlled single blind parallel trial. Thirty female subjects with mild dry skin were assigned randomly to two groups: one group used AEC/soap-based cleanser while the other group kept using their usual facial cleanser twice a day for 4 weeks in the winter season. Using a colored artificial sebum mixture, it was demonstrated that this cleanser washed sebum well. Following usage of this cleanser, their dry skin improved rather than worsen which was indicated by instrumental analysis and visual assessment. These improvements were recognized by subjects. These results suggest that AEC/soap-based cleanser washes off facial sebum well, but it has little effect on the induction of dry skin because of less penetration into stratum corneum. © 2014 Wiley Periodicals, Inc.

Absorption of ethanol, acetone, benzene and 1,2-dichloroethane through human skin in vitro: a test of diffusion model predictions.

PubMed

Gajjar, Rachna M; Kasting, Gerald B

2014-11-15

The overall goal of this research was to further develop and improve an existing skin diffusion model by experimentally confirming the predicted absorption rates of topically-applied volatile organic compounds (VOCs) based on their physicochemical properties, the skin surface temperature, and the wind velocity. In vitro human skin permeation of two hydrophilic solvents (acetone and ethanol) and two lipophilic solvents (benzene and 1,2-dichloroethane) was studied in Franz cells placed in a fume hood. Four doses of each (14)C-radiolabed compound were tested - 5, 10, 20, and 40μLcm(-2), corresponding to specific doses ranging in mass from 5.0 to 63mgcm(-2). The maximum percentage of radiolabel absorbed into the receptor solutions for all test conditions was 0.3%. Although the absolute absorption of each solvent increased with dose, percentage absorption decreased. This decrease was consistent with the concept of a stratum corneum deposition region, which traps small amounts of solvent in the upper skin layers, decreasing the evaporation rate. The diffusion model satisfactorily described the cumulative absorption of ethanol; however, values for the other VOCs were underpredicted in a manner related to their ability to disrupt or solubilize skin lipids. In order to more closely describe the permeation data, significant increases in the stratum corneum/water partition coefficients, Ksc, and modest changes to the diffusion coefficients, Dsc, were required. The analysis provided strong evidence for both skin swelling and barrier disruption by VOCs, even by the minute amounts absorbed under these in vitro test conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

Liposomogenic UV Absorbers are Water-Resistant on Pig Skin-A Model Study With Relevance for Sunscreens.

PubMed

Herzog, Bernd; Hüglin, Dietmar; Luther, Helmut

2017-02-01

An important property of sunscreens is their water resistance after the application on human skin. In this work, the hypothesis that UV absorber molecules which are able to form liposomes, so-called liposomogenic UV absorbers, show better water resistance on a pig skin model than UV-absorbing molecules lacking this ability was tested. The assumption behind is that molecules which can form liposomes are able to integrate into the stratum corneum lipids of the skin. Three different liposomogenic UV absorbers were synthesized and their behavior investigated, leading to the confirmation of the hypothesis. With one of the liposomogenic UV absorbers, it was possible to show the integration of the UV absorber molecules into the bilayers of another liposome consisting of phosphatidylcholine, supporting the assumption that liposomogenic UV absorbers exhibit improved water resistance because they integrate into the skin lipids. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Olive Oil, Sunflower Oil or no Oil for Baby Dry Skin or Massage: A Pilot, Assessor-blinded, Randomized Controlled Trial (the Oil in Baby SkincaRE [OBSeRvE] Study).

PubMed

Cooke, Alison; Cork, Michael J; Victor, Suresh; Campbell, Malcolm; Danby, Simon; Chittock, John; Lavender, Tina

2016-03-01

Topical oils on baby skin may contribute to development of childhood atopic eczema. A pilot, assessor-blinded, randomized controlled trial assessed feasibility of a definitive trial investigating their impact in neonates. One-hundred and fifteen healthy, full-term neonates were randomly assigned to olive oil, sunflower oil or no oil, twice daily for 4 weeks, stratified by family history of atopic eczema. We measured spectral profile of lipid lamellae, trans-epidermal water loss (TEWL), stratum corneum hydration and pH and recorded clinical observations, at baseline, and 4 weeks post-birth. Recruitment was challenging (recruitment 11.1%; retention 80%), protocol adherence reasonable (79-100%). Both oil groups had significantly improved hydration but significantly less improvement in lipid lamellae structure compared to the no oil group. There were no significant differences in TEWL, pH or erythema/skin scores. The study was not powered for clinical significance, but until further research is conducted, caution should be exercised when recommending oils for neonatal skin.

Antifungal Effect of Non-Woven Textiles Containing Polyhexamethylene Biguanide with Sophorolipid: A Potential Method for Tinea Pedis Prevention

PubMed Central

Sanada, Hiromi; Nakagami, Gojiro; Takehara, Kimie; Goto, Taichi; Ishii, Nanase; Yoshida, Satoshi; Ryu, Mizuyuki; Tsunemi, Yuichiro

2014-01-01

Tinea pedis is a preventable skin disease common in elderly or diabetic patients. Daily foot washing is effective for prevention, but can be difficult for many patients. Additionally, conventional methods cannot eliminate fungi within the stratum corneum, a common site for fungal invasion. This study investigates the antifungal effects, cytotoxicity, permeability, and efficacy of non-woven textiles containing polyhexamethylene biguanide (PHMB) mixed with sophorolipid. Permeability of PHMB with varying concentrations of sophorolipid was assessed via a cultured skin model. Stratum corneum PHMB concentration was quantified by polyvinylsulphuric acid potassium salt titration and cytotoxicity was assayed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Antifungal effects were evaluated via a new cultured skin/Trichophyton mentagrophytes model, with varying PHMB exposure duration. Clinically-isolated Trichophyton were applied to the feet of four healthy volunteers and then immediately treated with the following methods: washing with soap, a non-woven textile with PHMB, the textile without PHMB, or without washing. Fungal colony forming units (CFUs) were evaluated after one of these treatments were performed. Sophorolipid with various concentrations significantly facilitated PHMB permeation into the stratum corneum, which was not in a dose-dependent manner. Significant PHMB antifungal effects were achieved at 30 min, with low cytotoxicity. Textiles containing PHMB significantly reduced CFU of fungi in healthy volunteers to levels comparable to soap washing. Our results indicate the utility of this product for tinea pedis prevention in clinical settings. PMID:27429269

Antifungal Effect of Non-Woven Textiles Containing Polyhexamethylene Biguanide with Sophorolipid: A Potential Method for Tinea Pedis Prevention.

PubMed

Sanada, Hiromi; Nakagami, Gojiro; Takehara, Kimie; Goto, Taichi; Ishii, Nanase; Yoshida, Satoshi; Ryu, Mizuyuki; Tsunemi, Yuichiro

2014-04-08

Tinea pedis is a preventable skin disease common in elderly or diabetic patients. Daily foot washing is effective for prevention, but can be difficult for many patients. Additionally, conventional methods cannot eliminate fungi within the stratum corneum, a common site for fungal invasion. This study investigates the antifungal effects, cytotoxicity, permeability, and efficacy of non-woven textiles containing polyhexamethylene biguanide (PHMB) mixed with sophorolipid. Permeability of PHMB with varying concentrations of sophorolipid was assessed via a cultured skin model. Stratum corneum PHMB concentration was quantified by polyvinylsulphuric acid potassium salt titration and cytotoxicity was assayed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Antifungal effects were evaluated via a new cultured skin/Trichophyton mentagrophytes model, with varying PHMB exposure duration. Clinically-isolated Trichophyton were applied to the feet of four healthy volunteers and then immediately treated with the following methods: washing with soap, a non-woven textile with PHMB, the textile without PHMB, or without washing. Fungal colony forming units (CFUs) were evaluated after one of these treatments were performed. Sophorolipid with various concentrations significantly facilitated PHMB permeation into the stratum corneum, which was not in a dose-dependent manner. Significant PHMB antifungal effects were achieved at 30 min, with low cytotoxicity. Textiles containing PHMB significantly reduced CFU of fungi in healthy volunteers to levels comparable to soap washing. Our results indicate the utility of this product for tinea pedis prevention in clinical settings.

The effects of esterified solvents on the diffusion of a model compound across human skin: an ATR-FTIR spectroscopic study.

PubMed

McAuley, W J; Chavda-Sitaram, S; Mader, K T; Tetteh, J; Lane, M E; Hadgraft, J

2013-04-15

Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy has been used to investigate the effects of three fatty acid esters on skin permeation. Propylene glycol diperlargonate (DPPG), isopropyl myristate (IPM) and isostearyl isostearate (ISIS) were selected as pharmaceutically relevant solvents with a range of lipophilicities and cyanophenol (CNP) was used as a model drug. The resultant data were compared with that obtained when water was used as the solvent. The diffusion of CNP, DPPG and IPM across epidermis was successfully described by a Fickian model. When ISIS was used as a solvent Fickian behaviour was only obtained across isolated stratum corneum suggesting that the hydrophilic layers of the epidermis interfere with the permeation of the hydrophobic ISIS. The diffusion coefficients of CNP across epidermis in the different solvents were not significantly different. Using chemometric data analysis diffusion profiles for the solvents were deconvoluted from that of the skin and modelled. Each of these solvents was found to diffuse at a faster rate across the skin than CNP. DPPG considerably increased the concentration of CNP in the stratum corneum in comparison with the other solvents indicating strong penetration enhancer potential. In contrast IPM produced a similar CNP concentration in the stratum corneum to water with ISIS resulting in a lower CNP concentration suggesting negligible enhancement and penetration retardation effects for these two solvents respectively. Copyright © 2013 Elsevier B.V. All rights reserved.

Genetics Home Reference: Netherton syndrome

MedlinePlus

... stratum corneum. LEKT1 is also involved in normal hair growth, the development of lymphocytes in the thymus, and ... Loss of LEKT1 function also results in abnormal hair growth and immune dysfunction that leads to allergies, asthma, ...

Nuclear microprobe investigation of the penetration of ultrafine zinc oxide into intact and tape-stripped human skin

NASA Astrophysics Data System (ADS)

Szikszai, Z.; Kertész, Zs.; Bodnár, E.; Major, I.; Borbíró, I.; Kiss, Á. Z.; Hunyadi, J.

2010-06-01

Ultrafine metal oxides, such as titanium dioxide and zinc oxide are widely used in cosmetic and health products like sunscreens. These oxides are potent UV filters and the small particle size makes the product more transparent compared to formulations containing coarser particles. In the present work the penetration of ultrafine zinc oxide into intact and tape-stripped human skin was investigated using nuclear microprobe techniques, such as proton induced X-ray spectroscopy and scanning transmission ion microscopy. Our results indicate that the penetration of ultrafine zinc oxide, in a hydrophobic basis gel with 48 h application time, is limited to the stratum corneum layer of the intact skin. Removing the stratum corneum partially or entirely by tape-stripping did not cause the penetration of the particles into the deeper dermal layers; the zinc particles remained on the surface of the skin.

Management of Patients with Atopic Dermatitis: The Role of Emollient Therapy

PubMed Central

Catherine Mack Correa, M.; Nebus, Judith

2012-01-01

Atopic dermatitis is a common inflammatory skin disorder that afflicts a growing number of young children. Genetic, immune, and environmental factors interact in a complex fashion to contribute to disease expression. The compromised stratum corneum found in atopic dermatitis leads to skin barrier dysfunction, which results in aggravation of symptoms by aeroallergens, microbes, and other insults. Infants—whose immune system and epidermal barrier are still developing—display a higher frequency of atopic dermatitis. Management of patients with atopic dermatitis includes maintaining optimal skin care, avoiding allergic triggers, and routinely using emollients to maintain a hydrated stratum corneum and to improve barrier function. Flares of atopic dermatitis are often managed with courses of topical corticosteroids or calcineurin inhibitors. This paper discusses the role of emollients in the management of atopic dermatitis, with particular emphasis on infants and young children. PMID:23008699

Animal models for transdermal drug delivery.

PubMed

Panchagnula, R; Stemmer, K; Ritschel, W A

1997-06-01

The purpose of this investigation was to compare the permeation characteristics of two different compounds (extremely polar and nonpolar), i.e., tritium-labeled water (W) and 14C-labeled 7-hydroxycoumarin (7-OHC), among 16 different species, including human skin. Snake skin exhibited highest permeability for both W and 7-OHC. Permeability and lag time values of W and 7-OHC across Brattleboro rat and hairless guinea pig are very close to human skin. Skin thickness in micrometers (full thickness, epidermis and stratum corneum, and stratum corneum), and number of hair follicles present in each cm2 were determined for each species. There was no relationship between number of hair follicles and permeability values for both W and 7-OHC. The skin thickness (full) was related to the relative permeability values of W, whereas for 7-OHC it was not.

Surfactants have multi-fold effects on skin barrier function.

PubMed

Lemery, Emmanuelle; Briançon, Stéphanie; Chevalier, Yves; Oddos, Thierry; Gohier, Annie; Boyron, Olivier; Bolzinger, Marie-Alexandrine

2015-01-01

The stratum corneum (SC) is responsible for the barrier properties of the skin and the role of intercorneocyte skin lipids, particularly their structural organization, in controlling SC permeability is acknowledged. Upon contacting the skin, surfactants interact with the SC components leading to barrier damage. To improve knowledge of the effect of several classes of surfactant on skin barrier function at three different levels. The influence of treatments of human skin explants with six non-ionic and four ionic surfactant solutions on the physicochemical properties of skin was investigated. Skin surface wettability and polarity were assessed through contact angle measurements. Infrared spectroscopy allowed monitoring the SC lipid organization. The lipid extraction potency of surfactants was evaluated thanks to HPLC-ELSD assays. One anionic and one cationic surfactant increased the skin polarity by removing the sebaceous and epidermal lipids and by disturbing the organization of the lipid matrix. Another cationic surfactant displayed a detergency effect without disturbing the skin barrier. Several non-ionic surfactants disturbed the lipid matrix organization and modified the skin wettability without any extraction of the skin lipids. Finally two non-ionic surfactants did not show any effect on the investigated parameters or on the skin barrier. The polarity, the organization of the lipid matrix and the lipid composition of the skin allowed describing finely how surfactants can interact with the skin and disturb the skin barrier function.

Epidermal lipid in several cetacean species: ultrastructural observations.

PubMed

Pfeiffer, C J; Jones, F M

1993-09-01

The ultrastructure of the skin of four cetacean species, bottlenose dolphin (Tursiops truncatus) long-finned pilot whale (Globicephala melaena), humpback whale (Megaptera novaeangliae), and fin whale (Balaenoptera physalus) was investigated with particular reference to epidermal lipid. It has already been established that massive lipid reservoirs exist in whales, that the biochemical structures of cetacean lipids are unique, and that unusual intracellular lipid droplets appear in the epidermis. We report here some novel findings on scanning electron microscopic morphology of epidermal lipid, and on its ultrastructural morphology in general and specialized integumentary sites, including species not previously investigated. The intracellular epidermal lipid droplets were more extensive than lamellar body-derived intercellular lipid which is within the interstices of stratum externum cells. The intracellular droplets were spherical, highly variable in size ranging from 0.24 micron to 3.0 microns in diameter, appeared singly or were aggregated in cytoplasmic cavitations, and often were closely associated with epidermal cell nuclei. Evidence for exocytosis of the intracellular droplets was not observed. Significant numbers of intracellular lipid droplets are not observed in the epidermis of terrestrial mammals, so their presence is one of several aquatic specializations of the cetacean integument. Its full significance remains obscure, but it is more probably associated with epidermal cell metabolism than with secretion of lipid.

Estimation of within-stratum variance for sample allocation: Foreign commodity production forecasting

NASA Technical Reports Server (NTRS)

Chhikara, R. S.; Perry, C. R., Jr. (Principal Investigator)

1980-01-01

The problem of determining the stratum variances required for an optimum sample allocation for remotely sensed crop surveys is investigated with emphasis on an approach based on the concept of stratum variance as a function of the sampling unit size. A methodology using the existing and easily available information of historical statistics is developed for obtaining initial estimates of stratum variances. The procedure is applied to variance for wheat in the U.S. Great Plains and is evaluated based on the numerical results obtained. It is shown that the proposed technique is viable and performs satisfactorily with the use of a conservative value (smaller than the expected value) for the field size and with the use of crop statistics from the small political division level.

Skin penetration and antioxidant effect of cosmeto-textiles with gallic acid.

PubMed

Alonso, C; Martí, M; Barba, C; Lis, M; Rubio, L; Coderch, L

2016-03-01

In this work, the antioxidant gallic acid (GA) has been encapsulated in microspheres prepared with poly-ε-caprolactone (PCL) and incorporated into polyamide (PA) obtaining the cosmeto-textile. The topical application of the cosmeto-textile provides a reservoir effect in the skin delivery of GA. The close contact of the cosmeto-textile, containing microsphere-encapsulated GA (ME-GA), with the skin and their corresponding occlusion, may be the main reasons that explain the crossing of active principle (GA) through the skin barrier, located in the stratum corneum, and its penetration into the different compartments of the skin, epidermis and dermis. An ex vivo assessment was performed to evaluate the antioxidant effect of the ME-GA on the stratum corneum (SC) using the thiobarbituric acid-reactive species (TBARS) test. The test is based on a non-invasive ex vivo methodology that evaluates lipid peroxides formed in the outermost layers of the SC from human volunteers after UV radiation to determine the effectiveness of an antioxidant. In this case, a ME-GA cosmeto-textile or ME-GA formulation were applied to the skin in vivo and lipid peroxidation (LPO) in the horny layer were determined after UV irradiation. This methodology may be used as a quality control tool to determine ex vivo the percentage of LPO inhibition on human SC for a variety of antioxidants that are topically applied, in this case GA. Results show that LPO formation was inhibited in human SC when GA was applied directly or embedded in the cosmeto-textile, demonstrating the effectiveness of both applications. The percentage of LPO inhibition obtained after both topical applications was approximately 10% for the cosmeto-textile and 41% for the direct application of microspheres containing GA. This methodology could be used to determine the effectiveness of topically applied antioxidants encapsulated in cosmeto-textiles on human SC. Copyright © 2016 Elsevier B.V. All rights reserved.

Variation in the activities of late stage filaggrin processing enzymes, calpain-1 and bleomycin hydrolase, together with pyrrolidone carboxylic acid levels, corneocyte phenotypes and plasmin activities in non-sun-exposed and sun-exposed facial stratum corneum of different ethnicities.

PubMed

Raj, N; Voegeli, R; Rawlings, A V; Summers, B; Munday, M R; Lane, M E

2016-12-01

Knowledge of the ethnic differences and effects of photodamage on the relative amounts of natural moisturizing factor (NMF) together with filaggrin processing enzymes in facial stratum corneum is limited. Our aim was to characterize the activities of calpain-1 (C-1), bleomycin hydrolase (BH) and the levels of pyrrolidone carboxylic acid (PCA) as a marker for total NMF levels and to relate them to plasmin activities and corneocyte maturation. Enzyme activities, PCA levels and corneocyte maturation were determined from facial tape strippings of photoexposed cheek and photoprotected post-auricular areas (PA) of healthy Caucasian (C), Black African (BA) and albino African (AA) female subjects living in South Africa. PCA concentration levels were of the order AA > BA > C subjects, and the highest activities of BH were present in the AA subjects. BH activities were greater on the photoexposed sites for the BA and C subjects, but they were only numerically elevated in the AA subjects. Photoprotected sites had an increase in C-1 activity in pigmented groups (C and BA), whereas in the AA subjects, the opposite was measured. Plasmin activities were greater on the cheek compared with the PA site for the AA and C subjects, but the activity was low in the BA subjects. In both test sites, the AA, but not the BA and C subjects, had smaller, parakeratotic and less mature corneocytes. Variation in PCA levels has been found for different ethnic groups in this study (AA > BA > C subjects). The values in the AA subjects are surprising as one might expect that the lack of pigmentation, and thereby increased photodamage, might lead to lower levels. Increased BH, but not C-1 activity, was observed in the AA subjects indicating that BH is associated with PCA production to a greater extent. Surprisingly, corneocyte maturation is still impaired with elevated PCA levels in AA subjects. The higher levels of plasmin and BH activities on the cheeks, especially for AA and C subjects, suggest

Solar radiation (PAR and UVA) and water temperature in relation to biochemical performance of Gelidium corneum (Gelidiales, Rhodophyta) in subtidal bottoms off the Basque coast

NASA Astrophysics Data System (ADS)

Quintano, Endika; Ganzedo, Unai; Díez, Isabel; Figueroa, Félix L.; Gorostiaga, José M.

2013-10-01

Gelidium corneum (Hudson) J.V. Lamouroux is a very important primary producer in the Cantabrian coastal ecosystem. Some local declines in their populations have been recently detected in the Basque coast. Occurrences of yellowing and an unusual branch breakdown pattern have also been reported for some G. corneum populations. In order to gain further insight into those environmental stressors operating at a local scale, here we investigate if shallow subtidal populations of G. corneum living under potentially different conditions of irradiance (PAR and UVA) and water temperature exhibit differences in some biochemical indicators of stress, namely C:N, antioxidant activity (radical cation of 2,2‧-azino-bis (3-ethylbenzothiazoline-6-sulfonate); ABTS+ assay) and mycosporine-like amino acids (MAAs) (Asterine 330 and Palythine). We hypothesised that G. corneum subjected to higher ambient levels of irradiance and water temperature would show higher C:N ratios, lower antioxidant activity and higher MAA concentrations. Our results partially support this hypothesis. We found that G. corneum exposed to increased levels of irradiance (PAR, UVA) exhibited greater C:N ratios and lower antioxidant activity (higher IC50), whereas no relationship was found regarding MAAs. No differences in biochemical performance in relation to temperature were detected among G. corneum exposed to comparable high light. Similarly, G. corneum growing under lower UVA radiation levels showed no differences in any of the measured biochemical variables with regard to PAR and water temperature. These findings suggest that, among the environmental factors examined, UVA radiation may be an important driver in regulating the along-shore variation in G. corneum biochemical performance. Therefore, the role of irradiance, especially UV radiation, in potential future alterations in Cantabrian G. corneum populations cannot be ruled out as a potential underlying factor.

Glycerophospholipid Profiles of Bats with White-Nose Syndrome.

PubMed

Pannkuk, Evan L; McGuire, Liam P; Warnecke, Lisa; Turner, James M; Willis, Craig K R; Risch, Thomas S

2015-01-01

Pseudogymnoascus destructans is an ascomycetous fungus responsible for the disease dubbed white-nose syndrome (WNS) and massive mortalities of cave-dwelling bats. The fungus infects bat epidermal tissue, causing damage to integumentary cells and pilosebaceous units. Differences in epidermal lipid composition caused by P. destructans infection could have drastic consequences for a variety of physiological functions, including innate immune efficiency and water retention. While bat surface lipid and stratum corneum lipid composition have been described, the differences in epidermal lipid content between healthy tissue and P. destructans-infected tissue have not been documented. In this study, we analyzed the effect of wing damage from P. destructans infection on the epidermal polar lipid composition (glycerophospholipids [GPs] and sphingomyelin) of little brown bats (Myotis lucifugus). We hypothesized that infection would lead to lower levels of total lipid or higher oxidized lipid product proportions. Polar lipids from three damaged and three healthy wing samples were profiled by electrospray ionization tandem mass spectrometry. We found lower total broad lipid levels in damaged tissue, specifically ether-linked phospholipids, lysophospholipids, phosphatidylcholine, and phosphatidylethanolamine. Thirteen individual GP species from four broad GP classes were present in higher amounts in healthy tissue. Six unsaturated GP species were absent in damaged tissue. Our results confirm that P. destructans infection leads to altered lipid profiles. Clinical signs of WNS may include lower lipid levels and lower proportions of unsaturated lipids due to cellular and glandular damage.

Using infrared and Raman microspectroscopies to compare ex vivo involved psoriatic skin with normal human skin

NASA Astrophysics Data System (ADS)

Leroy, Marie; Lefèvre, Thierry; Pouliot, Roxane; Auger, Michèle; Laroche, Gaétan

2015-06-01

Psoriasis is a chronic dermatosis that affects around 3% of the world's population. The etiology of this autoimmune pathology is not completely understood. The barrier function of psoriatic skin is known to be strongly altered, but the structural modifications at the origin of this dysfunction are not clear. To develop strategies to reduce symptoms of psoriasis or adequate substitutes for modeling, a deep understanding of the organization of psoriatic skin at a molecular level is required. Infrared and Raman microspectroscopies have been used to obtain direct molecular-level information on psoriatic and healthy human skin biopsies. From the intensities and positions of specific vibrational bands, the lipid and protein distribution and the lipid order have been mapped in the different layers of the skin. Results showed a similar distribution of lipids and collagen for normal and psoriatic human skin. However, psoriatic skin is characterized by heterogeneity in lipid/protein composition at the micrometer scale, a reduction in the definition of skin layer boundaries and a decrease in lipid chain order in the stratum corneum as compared to normal skin. A global decrease of the structural organization is exhibited in psoriatic skin that is compatible with an alteration of its barrier properties.

Biometrological assessment of the preventive effect of a miconazole spray powder on athlete's foot.

PubMed

Piérard, G E; Wallace, R; De Doncker, P

1996-09-01

Prevention of athlete's foot is a difficult problem. Using non-invasive biometrological methods, we evaluated the changes induced in the stratum corneum by a 3-week treatment with miconazole spray powder. A total of 16 athletes apparently at risk of developing tinea pedis, but without any evidence for the disease at the time of inclusion, participated in the study. They applied the medicated powder to one foot daily, while the other foot remained untreated to serve as a control. No adverse events occurred. In comparison with the control site, the capacitance of the toeweb skin was significantly reduced by the treatment. The ex vivo bioassay of dermatophyte culture on stratum corneum demonstrated a significant inhibition of growth of Trichophyton mentagrophytes var. interdigital at the treated site. The results of this study provide indirect evidence that the regular use of miconazole spray powder decreases the risk of developing athlete's foot.

Transdermal delivery of therapeutic agent

NASA Technical Reports Server (NTRS)

Kwiatkowski, Krzysztof C. (Inventor); Hayes, Ryan T. (Inventor); Magnuson, James W. (Inventor); Giletto, Anthony (Inventor)

2008-01-01

A device for the transdermal delivery of a therapeutic agent to a biological subject that includes a first electrode comprising a first array of electrically conductive microprojections for providing electrical communication through a skin portion of the subject to a second electrode comprising a second array of electrically conductive microprojections. Additionally, a reservoir for holding the therapeutic agent surrounding the first electrode and a pulse generator for providing an exponential decay pulse between the first and second electrodes may be provided. A method includes the steps of piercing a stratum corneum layer of skin with two arrays of conductive microprojections, encapsulating the therapeutic agent into biocompatible charged carriers, surrounding the conductive microprojections with the therapeutic agent, generating an exponential decay pulse between the two arrays of conductive microprojections to create a non-uniform electrical field and electrokinetically driving the therapeutic agent through the stratum corneum layer of skin.

Skin physiology and textiles - consideration of basic interactions.

PubMed

Wollina, U; Abdel-Naser, M B; Verma, S

2006-01-01

The skin exerts a number of essential protective functions ensuring homeostasis of the whole body. In the present review barrier function of the skin, thermoregulation, antimicrobial defence and the skin-associated immune system are discussed. Barrier function is provided by the dynamic stratum corneum structure composed of lipids and corneocytes. The stratum corneum is a conditio sine qua non for terrestrial life. Impairment of barrier function can be due to injury and inflammatory skin diseases. Textiles, in particular clothing, interact with skin functions in a dynamic pattern. Mechanical properties like roughness of fabric surface are responsible for non-specific skin reactions like wool intolerance or keratosis follicularis. Thermoregulation, which is mediated by local blood flow and evaporation of sweat, is an important subject for textile-skin interactions. There are age-, gender- and activity-related differences in thermoregulation of skin that should be considered for the development of specifically designed fabrics. The skin is an important immune organ with non-specific and specific activities. Antimicrobial textiles may interfere with non-specific defence mechanisms like antimicrobial peptides of skin or the resident microflora. The use of antibacterial compounds like silver, copper or triclosan is a matter of debate despite their use for a very long period. Macromolecules with antimicrobial activity like chitosan that can be incorporated into textiles or inert material like carbon fibres or activated charcoal seem to be promising agents. Interaction of textiles with the specific immune system of skin is a rare event but may lead to allergic contact dermatitis. Electronic textiles and other smart textiles offer new areas of usage in health care and risk management but bear their own risks for allergies.

Early-life risk factors for occurrence of atopic dermatitis during the first year.

PubMed

Sugiyama, Mikio; Arakawa, Hirokazu; Ozawa, Kiyoshi; Mizuno, Takahisa; Mochizuki, Hiroyuki; Tokuyama, Kenichi; Morikawa, Akihiro

2007-03-01

In a prospective birth cohort study, we sought to identify perinatal predictors of the occurrence of atopic dermatitis in the first year of life. Associations of family history, infection during pregnancy, cord blood cytokine concentrations, and skin function parameters with atopic dermatitis were analyzed. Stratum corneum hydration was measured with an impedance meter until 5 days after delivery and again at 1 month. Complete data were obtained for 213 infants, including 27 diagnosed by a physician as having atopic dermatitis during their first year and 26 diagnosed as having infantile eczema during their first month. The risk of atopic dermatitis during the first year of life was related to maternal atopic dermatitis, lower concentrations of macrophage inflammatory protein-1beta in cord blood, and greater skin moisture in the surface and stratum corneum of the forehead and cheek at 1 month of age but not to viral or bacterial infection during pregnancy or breastfeeding. Paternal hay fever was associated negatively with the development of atopic dermatitis. High concentrations of interleukin-5, interleukin-17, and macrophage chemotactic protein-1 and only surface moisture in the cheek were associated with greater risk of infantile eczema in the first month. The association of atopic dermatitis in infancy with reduced neonatal macrophage inflammatory protein-1beta levels suggests a link with immature immune responses at birth. Stratum corneum barrier disruption in atopic dermatitis may involve impairment of cutaneous adaptation to extrauterine life. The majority of risk factors had different effects on infant eczema and atopic dermatitis, indicating different causes.

Reevaluation of the non-lesional dry skin in atopic dermatitis by acute barrier disruption: an abnormal permeability barrier homeostasis with defective processing to generate ceramide.

PubMed

Sugiura, Ayumi; Nomura, Tsuyoshi; Mizuno, Atsuko; Imokawa, Genji

2014-07-01

Atopic dermatitis is characterized by disruption of the cutaneous barrier due to reduced ceramide levels even in non-lesional dry skin. Following further acute barrier disruption by repeated tape strippings, we re-characterized the non-lesional dry skin of subjects with atopic dermatitis, which shows significantly reduced levels of barrier function and ceramide but not of beta-glucocerebrosidase activity. For the first time, we report an abnormal trans-epidermal water loss homeostasis in which delayed recovery kinetics of trans-epidermal water loss occurred on the first day during the 4 days after acute barrier disruption compared with healthy control skin. Interestingly, whereas the higher ceramide level in the stratum corneum of healthy control skin was further significantly up-regulated at 4 days post-tape stripping, the lower ceramide level in the stratum corneum of subjects with atopic dermatitis was not significantly changed. In a parallel study, whereas beta-glucocerebrosidase activity at 4 days post-tape stripping was significantly up-regulated in healthy control skin compared with before tape stripping, the level of that activity remained substantially unchanged in atopic dermatitis. These findings indicate that subjects with atopic dermatitis have a defect in sphingolipid-metabolic processing that generates ceramide in the interface between the stratum corneum and the epidermis. The results also support the notion that the continued disruption of barrier function in atopic dermatitis non-lesional skin is associated with the impaired homeostasis of a ceramide-generating process, which underscores an atopy-specific inflammation-triggered ceramide deficiency that is distinct from other types of dermatitis.

Effect of olive and sunflower seed oil on the adult skin barrier: implications for neonatal skin care.

PubMed

Danby, Simon G; AlEnezi, Tareq; Sultan, Amani; Lavender, Tina; Chittock, John; Brown, Kirsty; Cork, Michael J

2013-01-01

Natural oils are advocated and used throughout the world as part of neonatal skin care, but there is an absence of evidence to support this practice. The goal of the current study was to ascertain the effect of olive oil and sunflower seed oil on the biophysical properties of the skin. Nineteen adult volunteers with and without a history of atopic dermatitis were recruited into two randomized forearm-controlled mechanistic studies. The first cohort applied six drops of olive oil to one forearm twice daily for 5 weeks. The second cohort applied six drops of olive oil to one forearm and six drops of sunflower seed oil to the other twice daily for 4 weeks. The effect of the treatments was evaluated by determining stratum corneum integrity and cohesion, intercorneocyte cohesion, moisturization, skin-surface pH, and erythema. Topical application of olive oil for 4 weeks caused a significant reduction in stratum corneum integrity and induced mild erythema in volunteers with and without a history of atopic dermatitis. Sunflower seed oil preserved stratum corneum integrity, did not cause erythema, and improved hydration in the same volunteers. In contrast to sunflower seed oil, topical treatment with olive oil significantly damages the skin barrier, and therefore has the potential to promote the development of, and exacerbate existing, atopic dermatitis. The use of olive oil for the treatment of dry skin and infant massage should therefore be discouraged. These findings challenge the unfounded belief that all natural oils are beneficial for the skin and highlight the need for further research. © 2012 Wiley Periodicals, Inc.

Microbiome dynamics of human epidermis following skin barrier disruption

PubMed Central

2012-01-01

Background Recent advances in sequencing technologies have enabled metagenomic analyses of many human body sites. Several studies have catalogued the composition of bacterial communities of the surface of human skin, mostly under static conditions in healthy volunteers. Skin injury will disturb the cutaneous homeostasis of the host tissue and its commensal microbiota, but the dynamics of this process have not been studied before. Here we analyzed the microbiota of the surface layer and the deeper layers of the stratum corneum of normal skin, and we investigated the dynamics of recolonization of skin microbiota following skin barrier disruption by tape stripping as a model of superficial injury. Results We observed gender differences in microbiota composition and showed that bacteria are not uniformly distributed in the stratum corneum. Phylogenetic distance analysis was employed to follow microbiota development during recolonization of injured skin. Surprisingly, the developing neo-microbiome at day 14 was more similar to that of the deeper stratum corneum layers than to the initial surface microbiome. In addition, we also observed variation in the host response towards superficial injury as assessed by the induction of antimicrobial protein expression in epidermal keratinocytes. Conclusions We suggest that the microbiome of the deeper layers, rather than that of the superficial skin layer, may be regarded as the host indigenous microbiome. Characterization of the skin microbiome under dynamic conditions, and the ensuing response of the microbial community and host tissue, will shed further light on the complex interaction between resident bacteria and epidermis. PMID:23153041

Bed structure (frond bleaching, density and biomass) of the red alga Gelidium corneum under different irradiance levels

NASA Astrophysics Data System (ADS)

Quintano, E.; Díez, I.; Muguerza, N.; Figueroa, F. L.; Gorostiaga, J. M.

2017-12-01

In recent decades a decline in the foundation species Gelidium corneum (Hudson) J. V. Lamouroux has been detected along the Basque coast (northern Spain). This decline has been attributed to several factors, but recent studies have found a relationship between high irradiance and the biochemical and physiological stress of G. corneum. Since physiological responses to changes in light occur well before variations in morphology, the present study seeks to use a size-class demographic approach to investigate whether shallow subtidal populations of G. corneum off the Basque coast show different frond bleaching, density and biomass under different irradiance conditions. The results revealed that the bleaching incidence and cover were positively related to irradiance, whereas biomass was negatively related. The effect of the irradiance level on frond density was found to vary with size-class, i.e. fronds up to 15 cm showed greater densities under high light conditions (126.6 to 262.2 W m- 2) whereas the number of larger fronds (> 20 cm) per unit area was lower. In conclusion, the results of the present study suggest that irradiance might be a key factor for controlling along-shore bleaching, frond density and biomass in G. corneum. Further research should be carried out on the physiology of this canopy species in relation to its bed structure and on the interaction of irradiance and other abiotic (nutrients, temperature, wave energy) and biotic factors (grazing pressure).

Performance evaluation of multi-stratum resources integrated resilience for software defined inter-data center interconnect.

PubMed

Yang, Hui; Zhang, Jie; Zhao, Yongli; Ji, Yuefeng; Wu, Jialin; Lin, Yi; Han, Jianrui; Lee, Young

2015-05-18

Inter-data center interconnect with IP over elastic optical network (EON) is a promising scenario to meet the high burstiness and high-bandwidth requirements of data center services. In our previous work, we implemented multi-stratum resources integration among IP networks, optical networks and application stratums resources that allows to accommodate data center services. In view of this, this study extends to consider the service resilience in case of edge optical node failure. We propose a novel multi-stratum resources integrated resilience (MSRIR) architecture for the services in software defined inter-data center interconnect based on IP over EON. A global resources integrated resilience (GRIR) algorithm is introduced based on the proposed architecture. The MSRIR can enable cross stratum optimization and provide resilience using the multiple stratums resources, and enhance the data center service resilience responsiveness to the dynamic end-to-end service demands. The overall feasibility and efficiency of the proposed architecture is experimentally verified on the control plane of our OpenFlow-based enhanced SDN (eSDN) testbed. The performance of GRIR algorithm under heavy traffic load scenario is also quantitatively evaluated based on MSRIR architecture in terms of path blocking probability, resilience latency and resource utilization, compared with other resilience algorithms.

Analysis of in vivo penetration of textile dyes causing allergic reactions

NASA Astrophysics Data System (ADS)

Lademann, J.; Patzelt, A.; Worm, M.; Richter, H.; Sterry, W.; Meinke, M.

2009-10-01

Contact allergies to textile dyes are common and can cause severe eczema. In the present study, we investigated the penetration of a fluorescent textile dye, dissolved from a black pullover, into the skin of one volunteer during perspiration and nonperspiration. Previously, wearing this pullover had induced a severe contact dermatitis in an 82-year old woman, who was not aware of her sensitization to textile dyes. The investigations were carried out by in vivo laser scanning microscopy. It could be demonstrated that the dye was eluted from the textile material by sweat. Afterwards, the dye penetrated into the stratum corneum and into the hair follicles. Inside the hair follicles, the fluorescent signal was still detectable after 24 h, whereas it was not verifiable anymore in the stratum corneum, Laser scanning microscopy represents an efficient tool for in vivo investigation of the penetration and storage of topically applied substances and allergens into the human skin and reveals useful hints for the development and optimization of protection strategies.

A new methodology for evaluating the damage to the skin barrier caused by repeated application and removal of adhesive dressings.

PubMed

Waring, Mike; Bielfeldt, Stephan; Mätzold, Katja; Wilhelm, Klaus-Peter

2013-02-01

Chronic wounds require frequent dressing changes. Adhesive dressings used for this indication can be damaging to the stratum corneum, particularly in the elderly where the skin tends to be thinner. Understanding the level of damage caused by dressing removal can aid dressing selection. This study used a novel methodology that applied a stain to the skin and measured the intensity of that stain after repeated application and removal of a series of different adhesive types. Additionally, a traditional method of measuring skin barrier damage (transepidermal water loss) was also undertaken and compared with the staining methodology. The staining methodology and measurement of transepidermal water loss differentiated the adhesive dressings, showing that silicone adhesives caused least trauma to the skin. The staining methodology was shown to be as effective as transepidermal water loss in detecting damage to the stratum corneum and was shown to detect disruption of the barrier earlier than the traditional technique. © 2012 John Wiley & Sons A/S.

Gentle cleansing and moisturizing for patients with atopic dermatitis and sensitive skin.

PubMed

Cheong, Wai Kwong

2009-01-01

Atopic dermatitis is a common condition characterized by pruritus, inflammation, and dryness of the skin. Inflammation disrupts the barrier function of the stratum corneum, predisposing the skin to be dry, and increases susceptibility to irritants and secondary bacterial infection. Sensitive skin is common, reported by 40-50% of women and 30% of men in the US, Europe, and Japan. Basic requirements in managing eczema and sensitive skin include effective cleansers that do not compromise skin barrier integrity, alleviation of skin dryness, and restoration of skin barrier function through the use of therapeutic moisturizers. The selection of a skin cleanser is therefore an important part of managing these conditions. Studies have reported clinical improvement with the use of soap-free cleansers in combination with topical treatments. While topical corticosteroids and immunosuppressive agents are mainstays of treatment for atopic dermatitis, therapeutic moisturizers are important adjuncts. Moisturizers improve skin hydration, reduce susceptibility to irritation, restore the integrity of the stratum corneum, and enhance the efficacy of topical corticosteroids.

In-vivo dynamic characterization of microneedle skin penetration using optical coherence tomography

NASA Astrophysics Data System (ADS)

Enfield, Joey; O'Connell, Marie-Louise; Lawlor, Kate; Jonathan, Enock; O'Mahony, Conor; Leahy, Martin

2010-07-01

The use of microneedles as a method of circumventing the barrier properties of the stratum corneum is receiving much attention. Although skin disruption technologies and subsequent transdermal diffusion rates are being extensively studied, no accurate data on depth and closure kinetics of microneedle-induced skin pores are available, primarily due to the cumbersome techniques currently required for skin analysis. We report on the first use of optical coherence tomography technology to image microneedle penetration in real time and in vivo. We show that optical coherence tomography (OCT) can be used to painlessly measure stratum corneum and epidermis thickness, as well as microneedle penetration depth after microneedle insertion. Since OCT is a real-time, in-vivo, nondestructive technique, we also analyze skin healing characteristics and present quantitative data on micropore closure rate. Two locations (the volar forearm and dorsal aspect of the fingertip) have been assessed as suitable candidates for microneedle administration. The results illustrate the applicability of OCT analysis as a tool for microneedle-related skin characterization.

Enhancement of transdermal protein delivery by photothermal effect of gold nanorods coated on polysaccharide-based hydrogel.

PubMed

Haine, Aung Thu; Koga, Yuki; Hashimoto, Yuta; Higashi, Taishi; Motoyama, Keiichi; Arima, Hidetoshi; Niidome, Takuro

2017-10-01

Transdermal protein delivery is a useful and attractive method for protein therapy and dermal vaccination. However, this delivery method is restricted by the low permeability of the stratum corneum. The purpose of this study was to develop a transdermal delivery system for enhancement of protein permeability into the skin. First, we prepared a transparent gel patch made of polysaccharides with gold nanorods on the gel surface and fluorescein isothiocyanate-modified ovalbumin (FITC-OVA) inside. Next, the gel patch was placed on mouse skin to allow contact with the coated gold nanorods, and irradiated by a continuous-wave laser. The laser irradiation heated the gold nanorods and the skin temperature increased to 43°C, resulting in enhanced translocation of FITC-OVA into the skin. These results confirmed the capability of the transdermal protein delivery system to perforate the stratum corneum and thus facilitate the passage of proteins across the skin. Copyright © 2017 Elsevier B.V. All rights reserved.

Shaping the Skin: The Interplay of Mesoscale Geometry and Corneocyte Swelling

NASA Astrophysics Data System (ADS)

Evans, Myfanwy E.; Roth, Roland

2014-01-01

The stratum corneum, the outer layer of mammalian skin, provides a remarkable barrier to the external environment, yet it has highly variable permeability properties where it actively mediates between inside and out. On prolonged exposure to water, swelling of the corneocytes (skin cells composed of keratin intermediate filaments) is the key process by which the stratum corneum controls permeability and mechanics. As for many biological systems with intricate function, the mesoscale geometry is optimized to provide functionality from basic physical principles. Here we show that a key mechanism of corneocyte swelling is the interplay of mesoscale geometry and thermodynamics: given helical tubes with woven geometry equivalent to the keratin intermediate filament arrangement, the balance of solvation free energy and elasticity induces swelling of the system, importantly with complete reversibility. Our result remarkably replicates macroscopic experimental data of native through to fully hydrated corneocytes. This finding not only highlights the importance of patterns and morphology in nature but also gives valuable insight into the functionality of skin.

Transdermal Delivery of siRNA through Microneedle Array

NASA Astrophysics Data System (ADS)

Deng, Yan; Chen, Jiao; Zhao, Yi; Yan, Xiaohui; Zhang, Li; Choy, Kwongwai; Hu, Jun; Sant, Himanshu J.; Gale, Bruce K.; Tang, Tao

2016-02-01

Successful development of siRNA therapies has significant potential for the treatment of skin conditions (alopecia, allergic skin diseases, hyperpigmentation, psoriasis, skin cancer, pachyonychia congenital) caused by aberrant gene expression. Although hypodermic needles can be used to effectively deliver siRNA through the stratum corneum, the major challenge is that this approach is painful and the effects are restricted to the injection site. Microneedle arrays may represent a better way to deliver siRNAs across the stratum corneum. In this study, we evaluated for the first time the ability of the solid silicon microneedle array for punching holes to deliver cholesterol-modified housekeeping gene (Gapdh) siRNA to the mouse ear skin. Treating the ear with microneedles showed permeation of siRNA in the skin and could reduce Gapdh gene expression up to 66% in the skin without accumulation in the major organs. The results showed that microneedle arrays could effectively deliver siRNA to relevant regions of the skin noninvasively.

Infrared free electron laser enhanced transdermal drug delivery

NASA Astrophysics Data System (ADS)

Awazu, Kunio; Uchizono, Takeyuki; Suzuki, Sachiko; Yoshikawa, Kazushi

2005-08-01

It is necessary to control enhancement of transdermal drug delivery with non-invasive. The present study was investigated to assess the effectivity of enhancing the drug delivery by irradiating 6-μm region mid infrared free electron laser (MIR-FEL). The enhancement of transdermal drug (lidocaine) delivery of the samples (hairless mouse skin) irradiated with lasers was examined for flux (μg/cm2/h) and total penetration amount (μg/cm2) of lidocaine by High performance Liquid Chromatography (HPLC). The flux and total amount penatration date was enhanced 200-300 fold faster than the control date by the laser irradiation. FEL irradiating had the stratum corneum, and had the less thermal damage in epidermis. The effect of 6-μm region MIR-FEL has the enhancement of transdermal drug delivery without removing the stratum corneum because it has the less thermal damage. It leads to enhancement drug delivery system with non-invasive laser treatment.

Aconite poisoning following the percutaneous absorption of Aconitum alkaloids.

PubMed

Chan, Thomas Y K

2012-11-30

In vitro experiment using the modified Franz-type diffusion cell has demonstrated that the human skin is permeable to aconitine and mesaconitine. To characterise the risk of systemic toxicity following the topical applications of aconite tincture and raw aconite roots, relevant reports of percutaneous absorption of Aconitum alkaloids and aconite poisoning are reviewed. Published reports indicate that aconite tincture and raw aconite roots can be absorbed through the skin into systemic circulation to cause fatal and non-fatal aconite poisoning. Both aconite tincture and raw aconite roots contain very high concentrations of Aconitum alkaloids, which allow penetration of the stratum corneum along the diffusion gradient. The risk of systemic toxicity is even higher if Aconitum alkaloids are held in occlusive contact with the skin and the epidermis (stratum corneum) is already damaged. The public should be warned of the danger in using these topical aconite preparations and the risk of systemic toxicity following percutaneous absorption of Aconitum alkaloids. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Coffee polyphenols extracted from green coffee beans improve skin properties and microcirculatory function.

PubMed

Fukagawa, Satoko; Haramizu, Satoshi; Sasaoka, Shun; Yasuda, Yuka; Tsujimura, Hisashi; Murase, Takatoshi

2017-09-01

Coffee polyphenols (CPPs), including chlorogenic acid, exert various physiological activities. The purpose of this study was to investigate the effects of CPPs on skin properties and microcirculatory function in humans. In this double-blind, placebo-controlled study, 49 female subjects with mildly xerotic skin received either a test beverage containing CPPs (270 mg/100 mL/day) or a placebo beverage for 8 weeks. The ingestion of CPPs significantly lowered the clinical scores for skin dryness, decreased transepidermal water loss, skin surface pH, and increased stratum corneum hydration and the responsiveness of skin blood flow during local warming. Moreover, the amounts of free fatty acids and lactic acid in the stratum corneum significantly increased after the ingestion of CPPs. These results suggest that an 8-week intake of CPPs improve skin permeability barrier function and hydration, with a concomitant improvement in microcirculatory function, leading to efficacy in the alleviation of mildly xerotic skin.

Vibrational spectroscopy and microscopic imaging: novel approaches for comparing barrier physical properties in native and human skin equivalents.

PubMed

Yu, Guo; Zhang, Guojin; Flach, Carol R; Mendelsohn, Richard

2013-06-01

Vibrational spectroscopy and imaging have been used to compare barrier properties in human skin, porcine skin, and two human skin equivalents, Epiderm 200X with an enhanced barrier and Epiderm 200 with a normal barrier. Three structural characterizations were performed. First, chain packing and conformational order were compared in isolated human stratum corneum (SC), isolated porcine SC, and in the Epiderm 200X surface layers. The infrared (IR) spectrum of isolated human SC revealed a large proportion of orthorhombically packed lipid chains at physiological temperatures along with a thermotropic phase transition to a state with hexagonally packed chains. In contrast, the lipid phase at physiological temperatures in both porcine SC and in Epiderm 200X, although dominated by conformationally ordered chains, lacked significant levels of orthorhombic subcell packing. Second, confocal Raman imaging of cholesterol bands showed extensive formation of cholesterol-enriched pockets within the human skin equivalents (HSEs). Finally, IR imaging tracked lipid barrier dimensions as well as the spatial disposition of ordered lipids in human SC and Epiderm 200X. These approaches provide a useful set of experiments for exploring structural differences between excised human skin and HSEs, which in turn may provide a rationale for the functional differences observed among these preparations.

Therapeutic Implications of a Barrier-Based Pathogenesis of Atopic Dermatitis

PubMed Central

Wakefield, Joan S.

2015-01-01

Excessive Th2 cell signaling and IgE production play key roles in the pathogenesis of atopic dermatitis (AD). Yet, recent information suggests that the inflammation in AD instead is initiated by inherited insults to the barrier, including a strong association between mutations in FILAGGRIN and SPINK5 in Netherton syndrome, the latter of which provides an important clue that AD is provoked by excess serine protease activity. But acquired stressors to the barrier may also be required to initiate inflammation in AD, and in addition, microbial colonization by Staphylococcus aureus both amplifies inflammation, but also further stresses the barrier in AD. Therapeutic implications of these insights are as follows: While current therapy has been largely directed toward ameliorating Th2-mediated inflammation and/or pruritus, these therapies are fraught with short-term and potential long-term risks. In contrast, “barrier repair” therapy, with a ceramide-dominant triple-lipid mixture of stratum corneum lipids, is more logical, of proven efficacy, and it provides a far-improved safety profile. PMID:21174234

Unitary IPSPs evoked by interneurons at the stratum radiatum-stratum lacunosum-moleculare border in the CA1 area of the rat hippocampus in vitro

PubMed Central

Vida, Imre; Halasy, Katalin; Szinyei, Csaba; Somogyi, Peter; Buhl, Eberhard H

1998-01-01

Hippocampal non-principal neurons at the stratum radiatum-stratum lacunosum-moleculare border (R-LM interneurons) of the CA1 area may constitute several cell classes and have been implicated in the generation of GABAergic unitary IPSPs. Using biocytin-filled electrodes we recorded R-LM interneurons intracellularly in vitro and determined their postsynaptic effects in concomitantly recorded pyramidal cells. Light microscopic analysis revealed four populations of R-LM interneurons with distinct axons: (1) basket cells (n= 4) with axons predominantly ramifying in the pyramidal cell layer; (2) Schaffer collateral/commissural pathway-associated interneurons (n= 10) stratifying in stratum radiatum and, to a lesser extent, stratum oriens; (3) perforant pathway-associated interneurons (n= 6) innervating the perforant path termination zone in stratum lacunosum-moleculare of the CA1 area as well as equivalent portions of the dentate gyrus and subiculum; and (4) neurogliaform interneurons (n= 2) characterized by their dense, compact axonal and dendritic arbour. Random electron microscopic sampling of synaptic targets revealed a preponderance of pyramidal neurons as postsynaptic elements. Basket cells had a synaptic target preference for somata and proximal dendrites, whereas the remainder of R-LM interneurons innervated dendritic shafts and spines. The axon of dendrite-targeting cells formed up to six putative contacts with individual postsynaptic pyramidal cells. Anatomically recovered R-LM interneurons (n= 22) had a mean resting membrane potential of -56.7 ± 3.6 mV, a membrane time constant of 12.9 ± 7.7 ms and an input resistance of 86.4 ± 29.2 MΩ. Depolarizing current pulses generally elicited overshooting action potentials (70.8 ± 6.9 mV) which had a mean duration, when measured at half-amplitude, of 0.7 ± 0.1 ms. In response to prolonged (> 200 ms) depolarizing current pulses all R-LM interneurons displayed (a varying degree of) spike frequency adaptation. Basket

Appearance benefits of skin moisturization.

PubMed

Jiang, Z-X; DeLaCruz, J

2011-02-01

Skin hydration is essential for skin health. Moisturized skin is generally regarded as healthy and healthy looking. It is thus speculated that there may be appearance benefits of skin moisturization. This means that there are corresponding changes in the optical properties when skin is moisturized. The appearance of the skin is the result of light reflection, scattering and absorption at various skin layers of the stratum corneum, epidermis, dermis and beyond. The appearance benefits of skin moisturization are likely primarily due to the changes in the optical properties of the stratum corneum. We hypothesize that the major optical effect of skin moisturization is the decrease of light scattering at the skin surface, i.e., the stratum corneum. This decrease of surface scattering corresponds to an increase of light penetration into the deeper layers of the skin. An experiment was conducted to measure the corresponding change in skin spectral reflectance, the skin scattering coefficient and skin translucency with a change in skin hydration. In the experiment, skin hydration was decreased with the topical application of acetone and alcohol and increased with the topical application of known moisturizers and occlusives such as PJ. It was found that both the skin spectral reflectance and the skin scattering coefficient increased when the skin was dehydrated and decreased when the skin was hydrated. Skin translucency increased as the skin became moisturized. The results agree with the hypothesis that there is less light scattering at the skin surface and more light penetration into the deeper skin layers when the skin is moisturized. As a result, the skin appears darker, more pinkish and more translucent. © 2010 John Wiley & Sons A/S.

Effect of high-fat meal intake on the pharmacokinetic profile of ivermectin in Japanese patients with scabies.

PubMed

Miyajima, Atsushi; Hirota, Takashi; Sugioka, Akihito; Fukuzawa, Masao; Sekine, Mari; Yamamoto, Yosuke; Yoshimasu, Takashi; Kigure, Akira; Anata, Taichi; Noguchi, Wataru; Akagi, Keita; Komoda, Masayo

2016-09-01

Ivermectin (IVM) is used as an anthelmintic agent in many countries. To evaluate the effect of high-fat (HF) meal intake on the pharmacokinetics of IVM, a clinical trial was conducted in Japanese patients with scabies. The patients were administrated Stromectol(®) tablets in the fasted state, and after 1 week they were also administrated it after a HF meal (fed state). After the administration, IVM concentrations in plasma and the stratum corneum were determined. The geometric mean of fed/fasted ratio of area under IVM concentration-time curve (AUC) in plasma was 1.25 (90% confidence interval, 1.09-1.43), suggesting the tendency to increased absorption after a HF meal. The fed/fasted ratio of the maximum IVM concentration in the stratum corneum was well correlated with that in plasma. In addition, no serious adverse events were observed during the trial, while a mild increase of aspartate aminotransferase and alanine aminotransferase activity in plasma was observed under the fed state in two patients. The mean AUC of IVM in plasma of those two patients were approximately threefold higher than that of the other patients at that time. On the other hand, the treatment success rate was 76.9% at 7 days after the second administration, which was comparable with the expected level. The present study not only demonstrates that HF meal intake increases the IVM concentration in plasma and the stratum corneum in Japanese patients with scabies, but also suggests the possibility that HF meals increase the risk of hepatic dysfunction by the increased exposure of IVM. © 2016 Japanese Dermatological Association.

Water-filtered infrared-A (wIRA) can act as a penetration enhancer for topically applied substances

PubMed Central

Otberg, Nina; Grone, Diego; Meyer, Lars; Schanzer, Sabine; Hoffmann, Gerd; Ackermann, Hanns; Sterry, Wolfram; Lademann, Jürgen

2008-01-01

Background: Water-filtered infrared-A (wIRA) irradiation has been shown to enhance penetration of clinically used topically applied substances in humans through investigation of functional effects of penetrated substances like vasoconstriction by cortisone. Aim of the study: Investigation of the influence of wIRA irradiation on the dermatopharmacokinetics of topically applied substances by use of optical methods, especially to localize penetrating substances, in a prospective randomised controlled study in humans. Methods: The penetration profiles of the hydrophilic dye fluorescein and the lipophilic dye curcumin in separate standard water-in-oil emulsions were determined on the inner forearm of test persons by tape stripping in combination with spectroscopic measurements. Additionally, the penetration was investigated in vivo by laser scanning microscopy. Transepidermal water loss, hydration of the epidermis, and surface temperature were determined. Three different procedures (modes A, B, C) were used in a randomised order on three separate days of investigation in each of 12 test persons. In mode A, the two dyes were applied on different skin areas without water-filtered infrared-A (wIRA) irradiation. In mode B, the skin surface was irradiated with wIRA over 30 min before application of the two dyes (Hydrosun® radiator type 501, 10 mm water cuvette, orange filter OG590, water-filtered spectrum: 590–1400 nm with dominant amount of wIRA). In mode C, the two dyes were applied and immediately afterwards the skin was irradiated with wIRA over 30 min. In all modes, tape stripping started 30 min after application of the formulations. Main variable of interest was the ratio of the amount of the dye in the deeper (second) 10% of the stratum corneum to the amount of the dye in the upper 10% of the stratum corneum. Results: The penetration profiles of the hydrophilic fluorescein showed in case of pretreatment or treatment with wIRA (modes B and C) an increased

Immunohistochemical demonstration of keratins in the epidermal layers of the Malayan pangolin (Manis javanica), with remarks on the evolution of the integumental scale armour.

PubMed

Meyer, W; Liumsiricharoen, M; Suprasert, A; Fleischer, L G; Hewicker-Trautwein, M

2013-09-16

Using immunohistochemistry, the study demonstrates the distribution of keratins (pan-keratin with CK1-8, 10, 14-16, 19; keratins CK1, 5, 6, 9, 10; hair keratins AE13, AE14) in the epidermis of the Malayan pangolin (Manis javanica). A varying reaction spectrum was observed for pan-keratin, with body region-dependent negative to very strong reaction intensities. The dorsolateral epidermis exhibited positive reactions only in its vital layers, whereas the abdominal epidermis showed strong positive reactions in the soft two outer strata. The single acidic and basic-to-neutral (cyto)keratins produced clear variations compared to the pan-keratin tinging. E.g., CK1 appeared in all epidermal layers of both body regions, except for the ventral stratum corneum, whereas CK5, 6, 9, 10 were restricted to the soft ventral epidermis. Here, distinctly positive reactions were confined to the stratum granulosum, except for CK6 that appeared in the soft stratum corneum. A different staining pattern was obvious for the hair keratins, i.e., positive reactions of AE13 concentrated only in the granular layer of the dorsal epidermis. In the abdominal epidermis, remarkable tinging for AE14 was visible in the stratum basale, decreasing toward the corneal layer, but was also found in the outer root sheath cells of the hair follicles in the ventral body part. Our findings are discussed related to the evolution of the horny dorsal scales of the pangolin, which may have started from the tail root, projecting forward to the head.

A model for quantitative evaluation of skin damage at adhesive wound dressing removal.

PubMed

Matsumura, Hajime; Ahmatjan, Niyaz; Ida, Yukiko; Imai, Ryutaro; Wanatabe, Katsueki

2013-06-01

The removal of adhesive wound dressings from the wound surface involves a risk of damaging the intact stratum corneum and regenerating epithelium. Pain associated with the removal of wound dressings is a major issue for patients and medical personnel. Recently, wound dressings coated with a silicone adhesive have been developed to reduce such skin damage and pain on removal and they have received good evaluation in various clinical settings. However, there is neither a standard method to quantify whether or not the integrity of the stratum corneum and regenerating epithelium is retained or if both structures are damaged by the removal of wound dressings, nor are there standardised values with which to assess skin damage. We applied six different types of adhesive wound dressing on plain copy paper printed with black ink by a laser printer, removed the dressings, examined the adhesive-coated surface of the wound dressings using a high-power videoscope, and examined the stripped areas. Wound dressings coated with a silicone adhesive showed significantly less detachment of the stratum corneum and regenerating epithelium, followed by those coated with polyurethane, hydrocolloid, and acrylic adhesives. The assessment method utilised in this study revealed distinct differences between wound dressing types, but less variation in the evaluation outcome of each type. This assessment method may be useful for the evaluation of adhesive wound dressings, particularly during product development. However, further studies will be needed to examine the effectiveness of this assessment method in the clinical setting because the adherent properties of polyurethane and hydrocolloid adhesives may be altered by the absorption of water from the skin. © 2012 The Authors. International Wound Journal © 2012 John Wiley & Sons Ltd and Medicalhelplines.com Inc.

Brian Barry: innovative contributions to transdermal and topical drug delivery.

PubMed

Williams, A C

2013-01-01

Brian Barry published over 300 research articles across topics ranging from colloid science, vasoconstriction and the importance of thermodynamics in dermal drug delivery to exploring the structure and organisation of the stratum corneum barrier lipids and numerous strategies for improving topical and transdermal drug delivery, including penetration enhancers, supersaturation, coacervation, eutectic formation and the use of varied liposomes. As research in the area blossomed in the early 1980s, Brian wrote the book that became essential reading for both new and established dermal delivery scientists, explaining the background mathematics and principles through to formulation design. Brian also worked with numerous scientists, as collaborators and students, who have themselves taken his rigorous approach to scientific investigation into their own research groups. This paper can only describe a small fraction of the many significant contributions that Brian made to the field during his 40-year academic career.

Glycosylation facilitates transdermal transport of macromolecules

PubMed Central

Pino, Christopher J.; Gutterman, Jordan U.; Vonwil, Daniel; Mitragotri, Samir; Shastri, V. Prasad

2012-01-01

Stratum corneum, the outermost layer of skin, allows transport of only low-molecular weight (<500) lipophilic solutes. Here, we report a surprising finding that avicins (Avs), a family of naturally occurring glycosylated triterpenes with a molecular weight > 2,000, exhibit skin permeabilities comparable to those of small hydrophobic molecules, such as estradiol. Systematic fragmentation of the Av molecule shows that deletion of the outer monoterpene results in a 62% reduction in permeability, suggesting an important role for this motif in skin permeation. Further removal of the tetrasaccharide residue results in a further reduction of permeability by 79%. These results, taken in sum, imply that synergistic effects involving both hydrophobic and hydrophilic residues may hold the key in facilitating translocation of Avs across skin lipids. In addition to exhibiting high permeability, Avs provided moderate enhancements of skin permeability of estradiol and polysaccharides, including dextran and inulin but not polyethylene glycol. PMID:23236155

Acral peeling skin syndrome in two East-African siblings: case report.

PubMed

Kiprono, Samson K; Chaula, Baraka M; Naafs, Bernard; Masenga, John E

2012-03-19

Acral peeling skin syndrome is a rare autosomal recessive genodermatosis due to a missense mutation in transglutaminase 5. The skin peeling occurs at the separation of the stratum corneum from the stratum granulosum. We present a case of two siblings who developed continuous peeling of the palms and soles from the first year of life. This peeling was more severe on the soles than palms and on younger sibling than elder sibling. Peeling is worsened by occlusion and sweating. Sporadic cases of Acral Peeling Skin Syndrome occur in African population. There is variability in time of presentation and clinical severity even within families.

Production and characterization of cosmetic nanoemulsions containing Opuntia ficus-indica (L.) mill extract as moisturizing agent.

PubMed

Ribeiro, Renato Cesar de Azevedo; Barreto, Stella Maria de Andrade Gomes; Ostrosky, Elissa Aarantes; da Rocha-Filho, Pedro Alves; Veríssimo, Lourena Mafra; Ferrari, Márcio

2015-02-02

This study aimed to produce and characterize an oil in water (O/W) nanoemulsion containing Opuntia ficus-indica (L.) Mill hydroglycolic extract, as well as evaluate its preliminary and accelerated thermal stability and moisturizing efficacy. The formulations containing 0.5% of xanthan gum (FX) and 0.5% of xanthan gum and 1% of Opuntia ficus-indica MILL extract (FXE) were white, homogeneus and fluid in aspect. Both formulations were stable during preliminary and accelerated stability tests. FX and FXE presented a pH compatible to skin pH (4.5-6.0); droplet size varying from 92.2 to 233.6 nm; a polydispersion index (PDI) around 0.200 and a zeta potential from -26.71 to -47.01 mV. FXE was able to increase the water content of the stratum corneum for 5 h after application on the forearm. The O/W nanoemulsions containing 1% of Opuntia ficus-indica (L.) Mill extract presented suitable stability for at least for 60 days. Besides, this formulation was able to increase the water content of stratum corneum, showing its moisturizing efficacy.

Biochemical changes in desmosomes of bovine muzzle epidermis during differentiation.

PubMed

Konohana, A; Konohana, I; Roberts, G P; Marks, R

1987-10-01

Biochemical changes taking place in desmosomes during differentiation have been studied. Bovine muzzle epidermis was sliced horizontally into 6 layers, 0.2 mm thick, and desmosomes were isolated from each layer. These were then analyzed by polyacrylamide gel electrophoresis. The electrophoretic patterns of desmosomal proteins from the 6 layers were found to be qualitatively similar to each other, but there was an increase in the ratio of the amount of 150 kD glycoprotein (desmoglein I) relative to 240 and 210 kD proteins (desmoplakins) in the upper layers of the epidermis. This finding was supported by the similar increase observed in electrophoretic patterns of proteins extracted directly from each layer of the epidermis in electrophoretic sample buffer. In order to study the fate of desmosomal components in the stratum corneum, serial skin surface biopsies were stained with antisera against desmosomal components using indirect immunofluorescence techniques. This experiment showed that desmosomal proteins and glycoproteins persist in the stratum corneum but quantitatively decrease in the outer layers. This decrease may play a significant role in desquamation.

A histomorphological study of sarcoptic acariasis in the dog: 19 cases.

PubMed

Morris, D O; Dunstan, R W

1996-01-01

Nineteen cases of canine sarcoptic acariasis (Sarcoptes scabiei var. canis) were diagnosed histologically by identifying sarcoptic mites present in the stratum corneum. The inflammatory responses to these mites could be staged as early, fully developed, or late lesions. No histomorphological features were identified that could serve as reliable markers of infestation in the absence of a sectioned mite.

Diversity and wiring variability of visual local neurons in the Drosophila medulla M6 stratum

PubMed Central

Chin, An-Lun; Lin, Chih-Yung; Fu, Tsai-Feng; Dickson, Barry J; Chiang, Ann-Shyn

2014-01-01

Local neurons in the vertebrate retina are instrumental in transforming visual inputs to extract contrast, motion, and color information and in shaping bipolar-to-ganglion cell transmission to the brain. In Drosophila, UV vision is represented by R7 inner photoreceptor neurons that project to the medulla M6 stratum, with relatively little known of this downstream substrate. Here, using R7 terminals as references, we generated a 3D volume model of the M6 stratum, which revealed a retinotopic map for UV representations. Using this volume model as a common 3D framework, we compiled and analyzed the spatial distributions of more than 200 single M6-specific local neurons (M6-LNs). Based on the segregation of putative dendrites and axons, these local neurons were classified into two families, directional and nondirectional. Neurotransmitter immunostaining suggested a signal routing model in which some visual information is relayed by directional M6-LNs from the anterior to the posterior M6 and all visual information is inhibited by a diverse population of nondirectional M6-LNs covering the entire M6 stratum. Our findings suggest that the Drosophila medulla M6 stratum contains diverse LNs that form repeating functional modules similar to those found in the vertebrate inner plexiform layer. J. Comp. Neurol. 522:3795–3816, 2014. © 2014 Wiley Periodicals, Inc. PMID:24782245

Diversity and wiring variability of visual local neurons in the Drosophila medulla M6 stratum.

PubMed

Chin, An-Lun; Lin, Chih-Yung; Fu, Tsai-Feng; Dickson, Barry J; Chiang, Ann-Shyn

2014-12-01

Local neurons in the vertebrate retina are instrumental in transforming visual inputs to extract contrast, motion, and color information and in shaping bipolar-to-ganglion cell transmission to the brain. In Drosophila, UV vision is represented by R7 inner photoreceptor neurons that project to the medulla M6 stratum, with relatively little known of this downstream substrate. Here, using R7 terminals as references, we generated a 3D volume model of the M6 stratum, which revealed a retinotopic map for UV representations. Using this volume model as a common 3D framework, we compiled and analyzed the spatial distributions of more than 200 single M6-specific local neurons (M6-LNs). Based on the segregation of putative dendrites and axons, these local neurons were classified into two families, directional and nondirectional. Neurotransmitter immunostaining suggested a signal routing model in which some visual information is relayed by directional M6-LNs from the anterior to the posterior M6 and all visual information is inhibited by a diverse population of nondirectional M6-LNs covering the entire M6 stratum. Our findings suggest that the Drosophila medulla M6 stratum contains diverse LNs that form repeating functional modules similar to those found in the vertebrate inner plexiform layer. © 2014 Wiley Periodicals, Inc.

The application of ATR-FTIR spectroscopy and multivariate data analysis to study drug crystallisation in the stratum corneum.

PubMed

Goh, Choon Fu; Craig, Duncan Q M; Hadgraft, Jonathan; Lane, Majella E

2017-02-01

Drug permeation through the intercellular lipids, which pack around and between corneocytes, may be enhanced by increasing the thermodynamic activity of the active in a formulation. However, this may also result in unwanted drug crystallisation on and in the skin. In this work, we explore the combination of ATR-FTIR spectroscopy and multivariate data analysis to study drug crystallisation in the skin. Ex vivo permeation studies of saturated solutions of diclofenac sodium (DF Na) in two vehicles, propylene glycol (PG) and dimethyl sulphoxide (DMSO), were carried out in porcine ear skin. Tape stripping and ATR-FTIR spectroscopy were conducted simultaneously to collect spectral data as a function of skin depth. Multivariate data analysis was applied to visualise and categorise the spectral data in the region of interest (1700-1500cm -1 ) containing the carboxylate (COO - ) asymmetric stretching vibrations of DF Na. Spectral data showed the redshifts of the COO - asymmetric stretching vibrations for DF Na in the solution compared with solid drug. Similar shifts were evident following application of saturated solutions of DF Na to porcine skin samples. Multivariate data analysis categorised the spectral data based on the spectral differences and drug crystallisation was found to be confined to the upper layers of the skin. This proof-of-concept study highlights the utility of ATR-FTIR spectroscopy in combination with multivariate data analysis as a simple and rapid approach in the investigation of drug deposition in the skin. The approach described here will be extended to the study of other actives for topical application to the skin. Copyright © 2016 Elsevier B.V. All rights reserved.

Relationship between soft stratum thickness and predominant frequency of ground based on microtremor observation data

NASA Astrophysics Data System (ADS)

Chia, Kenny; Lau, Tze Liang

2017-07-01

Despite categorized as low seismicity group, until being affected by distant earthquake ground motion from Sumatra and the recent 2015 Sabah Earthquake, Malaysia has come to realize that seismic hazard in the country is real and has the potential to threaten the public safety and welfare. The major concern in this paper is to study the effect of local site condition, where it could amplify the magnitude of ground vibration at sites. The aim for this study is to correlate the thickness of soft stratum with the predominant frequency of soil. Single point microtremor measurements were carried out at 24 selected points where the site investigation reports are available. Predominant period and frequency at each site are determined by Nakamura's method. The predominant period varies from 0.22 s to 0.98 s. Generally, the predominant period increases when getting closer to the shoreline which has thicker sediments. As far as the thickness of the soft stratum could influence the amplification of seismic wave, the advancement of micotremor observation to predict the thickness of soft stratum (h) from predominant frequency (fr) is of the concern. Thus an empirical relationship h =54.917 fr-1.314 is developed based on the microtremor observation data. The empirical relationship will be benefited in the prediction of thickness of soft stratum based on microtremor observation for seismic design with minimal cost compared to conventional boring method.

Orally administered hyaluronan affects skin dryness and epidermal thickening in photoaged hairless mice.

PubMed

Kawada, Chinatsu; Kimura, Mamoru; Masuda, Yasunobu; Nomura, Yoshihiro

2016-06-01

The oral administration of hyaluronans (HAs) (molecular weight, 300k and less than 10k) to photoaged hairless mice increased the moisture content of the stratum corneum and decreased the epidermal thickness, respectively. Furthermore, orally administered HAs suppressed the low-molecular weight of HA content of the skin. This study indicates oral administered HAs may ameliorate the skin condition resulting from photoaging.

A Case of Peeling Skin Syndrome.

PubMed

Singhal, Anil K; Yadav, Devendra K; Soni, Bajrang; Arya, Savita

2017-01-01

Peeling skin syndrome is a very rare autosomal recessive disease characterized by widespread painless peeling of the skin in superficial sheets. Etiology is still unknown with an autosomal recessive inheritance. Less than 100 cases have been reported in the medical literature. We present a 32-year-old man having asymptomatic peeling of skin since birth. Sheets of skin were peeling from his neck, trunk, and extremities, following friction or rubbing especially if pre-soaked in water but sparing palm and soles. Histologically, there was epidermal separation at the level of stratum corneum, just above the stratum granulosum. This case is being presented due to its rarity.

A Case of Peeling Skin Syndrome

PubMed Central

Singhal, Anil K.; Yadav, Devendra K.; Soni, Bajrang; Arya, Savita

2017-01-01

Peeling skin syndrome is a very rare autosomal recessive disease characterized by widespread painless peeling of the skin in superficial sheets. Etiology is still unknown with an autosomal recessive inheritance. Less than 100 cases have been reported in the medical literature. We present a 32-year-old man having asymptomatic peeling of skin since birth. Sheets of skin were peeling from his neck, trunk, and extremities, following friction or rubbing especially if pre-soaked in water but sparing palm and soles. Histologically, there was epidermal separation at the level of stratum corneum, just above the stratum granulosum. This case is being presented due to its rarity. PMID:28584761

Acral peeling skin syndrome in two East-African siblings: case report

PubMed Central

2012-01-01

Background Acral peeling skin syndrome is a rare autosomal recessive genodermatosis due to a missense mutation in transglutaminase 5. The skin peeling occurs at the separation of the stratum corneum from the stratum granulosum. Case presentation We present a case of two siblings who developed continuous peeling of the palms and soles from the first year of life. This peeling was more severe on the soles than palms and on younger sibling than elder sibling. Peeling is worsened by occlusion and sweating. Conclusions Sporadic cases of Acral Peeling Skin Syndrome occur in African population. There is variability in time of presentation and clinical severity even within families. PMID:22429841

Natural (Mineral, Vegetable, Coconut, Essential) Oils and Contact Dermatitis.

PubMed

Verallo-Rowell, Vermén M; Katalbas, Stephanie S; Pangasinan, Julia P

2016-07-01

Natural oils include mineral oil with emollient, occlusive, and humectant properties and the plant-derived essential, coconut, and other vegetable oils, composed of triglycerides that microbiota lipases hydrolyze into glycerin, a potent humectant, and fatty acids (FAs) with varying physico-chemical properties. Unsaturated FAs have high linoleic acid used for synthesis of ceramide-I linoleate, a barrier lipid, but more pro-inflammatory omega-6:-3 ratios above 10:1, and their double bonds form less occlusive palisades. VCO FAs have a low linoleic acid content but shorter and saturated FAs that form a more compact palisade, more anti-inflammatory omega-6:-3 ratio of 2:1, close to 7:1 of olive oil, which disrupts the skin barrier, otherwise useful as a penetration enhancer. Updates on the stratum corneum illustrate how this review on the contrasting actions of NOs provide information on which to avoid and which to select for barrier repair and to lower inflammation in contact dermatitis genesis.

Estimation of maximum transdermal flux of nonionized xenobiotics from basic physicochemical determinants

PubMed Central

Milewski, Mikolaj; Stinchcomb, Audra L.

2012-01-01

An ability to estimate the maximum flux of a xenobiotic across skin is desirable both from the perspective of drug delivery and toxicology. While there is an abundance of mathematical models describing the estimation of drug permeability coefficients, there are relatively few that focus on the maximum flux. This article reports and evaluates a simple and easy-to-use predictive model for the estimation of maximum transdermal flux of xenobiotics based on three common molecular descriptors: logarithm of octanol-water partition coefficient, molecular weight and melting point. The use of all three can be justified on the theoretical basis of their influence on the solute aqueous solubility and the partitioning into the stratum corneum lipid domain. The model explains 81% of the variability in the permeation dataset comprised of 208 entries and can be used to obtain a quick estimate of maximum transdermal flux when experimental data is not readily available. PMID:22702370

Salicylic acid peels for the treatment of acne vulgaris in Asian patients.

PubMed

Lee, Ho-Sup; Kim, Il-Hwan

2003-12-01

Salicylic acid peels have been introduced as a useful modality in acne treatment. Few studies have examined its efficacy and safety, especially in darker skin. To assess the efficacy and safety of salicylic acid peels as a treatment for acne vulgaris in Asian patients. Thirty-five Korean patients with facial acne were treated with 30% salicylic acid peels biweekly for 12 weeks. Lesion counts and Dr. Cunliffe's score were assessed by a blinded evaluator. Safety assessments and patient's evaluations were also recorded. Both inflammatory and noninflammatory acne lesion counts were decreased in proportion to the duration of treatment. Dr. Cunliffe's acne grade was statistically significantly decreased after treatment. The side effects were tolerable in most cases, and all patients were pleased with their peel results. Stratum corneum hydration, skin surface lipid, skin pH, and transepidermal water loss were unchanged from baseline levels. Salicylic acid peels are an effective and safe therapy for acne vulgaris in Asian patients.

Aspects relating to stability of modified passive stratum on TiO2 nanostructure

NASA Astrophysics Data System (ADS)

Ionita, Daniela; Mazare, Anca; Portan, Diana; Demetrescu, Ioana

2011-04-01

Two kinds of nanotube structures differing from the point of view of their dimensions were obtained using anodizing in two different fluoride electrolytes and these structures were investigated regarding stability. The nanotubes have diameters of around 100 and 65 nm, respectively, and the testing solutions were simulated body fluids (SBF) and NaCl 0.9%. As stability experiments, cyclic voltammetry was performed and ions release was measured. The quantity of released cations in time as a kinetic aspect of passive stratum behavior was followed with an inductively coupled plasma mass spectrometer (ICP-MS) and apatite forming in SBF was found with infrared spectra. This study led to a comparison between the modification and the behavior of passive stratum on nanotubes as a function of their diameters.

Determination of the thickness and structure of the skin barrier by in vivo laser scanning microscopy

NASA Astrophysics Data System (ADS)

Lademann, J.; Richter, H.; Astner, S.; Patzelt, A.; Knorr, F.; Sterry, W.; Antoniou, Ch

2008-04-01

Normal skin barrier function is an essential aspect of skin homeostasis and regeneration. Dynamic inflammatory, proliferative and neoplastic skin processes such as wound healing, psoriasis and contact dermatitis are associated with a significant disruption of the skin barrier. In recent years, there has been increasing interest in evaluating cosmetic and pharmacologic products for their ability to restore these protective properties. The gold standard for characterization of barrier function has been the measurement of the transepidermal water loss, however the disadvantage of this method is its interference with several endogenous and exogenous factors such as hydration, perspiration and topically applied substances. This study was aimed to test the clinical applicability of a fluorescence confocal laser scanning microscope (LSM) for a systematic morphologic analysis of the structure, integrity and thickness of the stratum corneum in 10 otherwise healthy volunteers. The influence of skin treatment with commercial moisturizing cream on skin barrier function was evaluated in serial non-invasive examinations. Our findings showed that in vivo LSM may represent a simple and efficient method for the characterization of skin barrier properties, such as the thickness and hydration of the stratum corneum.

Biophysical effects of repetitive removal of adhesive dressings on peri-ulcer skin.

PubMed

Zillmer, R; Agren, M S; Gottrup, F; Karlsmark, T

2006-05-01

To study the effect of repeated removal of four different adhesive dressings on peri-ulcer skin using quantitative non-invasive techniques. Forty-five patients with open (n = 29) or healed (n = 16) venous leg ulcers were included. Peri-ulcer skin was treated for 14 days with patches of two different hydrocolloid-based adhesive dressings, one polyurethane adhesive and one soft silicone adhesive dressing. Normal skin of the patients' ventral forearm was also treated identically. Adhesive patches of the dressings were replaced every second day. The skin barrier function was assessed by measuring transepidermal water loss and stratum corneum hydration by measuring electrical conductance. Thirty-nine patients completed the study. The hydrocolloid adhesives increased transepidermal water loss and conductance while the polyurethane and soft silicone adhesives did not influence these parameters significantly compared with adjacent non-treated peri-ulcer skin. For normal forearm skin, similar relative effects among the four adhesives were found. Repetitive treatment with hydrocolloid-based adhesive dressings induced major functional alterations of the stratum corneum. In contrast, a polyurethane adhesive and a soft silicone adhesive dressing did not alter transepidermal water loss or conductance of peri-ulcer skin.

Polymeric films loaded with vitamin E and aloe vera for topical application in the treatment of burn wounds.

PubMed

Pereira, Gabriela Garrastazu; Guterres, Sílvia Stanisçuaki; Balducci, Anna Giulia; Colombo, Paolo; Sonvico, Fabio

2014-01-01

Burns are serious traumas related to skin damage, causing extreme pain and possibly death. Natural drugs such as Aloe vera and vitamin E have been demonstrated to be beneficial in formulations for wound healing. The aim of this work is to develop and evaluate polymeric films containing Aloe vera and vitamin E to treat wounds caused by burns. Polymeric films containing different quantities of sodium alginate and polyvinyl alcohol (PVA) were characterized for their mechanical properties and drug release. The polymeric films, which were produced, were thin, flexible, resistant, and suitable for application on damaged skin, such as in burn wounds. Around 30% of vitamin E acetate was released from the polymeric films within 12 hours. The in vivo experiments with tape stripping indicated an effective accumulation in the stratum corneum when compared to a commercial cream containing the same quantity of vitamin E acetate. Vitamin E acetate was found in higher quantities in the deep layers of the stratum corneum when the film formulation was applied. The results obtained show that the bioadhesive films containing vitamin E acetate and Aloe vera could be an innovative therapeutic system for the treatment of burns.

Recent Advances in Skin Penetration Enhancers for Transdermal Gene and Drug Delivery.

PubMed

Amjadi, Morteza; Mostaghaci, Babak; Sitti, Metin

2017-01-01

There is a growing interest in transdermal delivery systems because of their noninvasive, targeted, and on-demand delivery of gene and drugs. However, efficient penetration of therapeutic compounds into the skin is still challenging largely due to the impermeability of the outermost layer of the skin, known as stratum corneum. Recently, there have been major research activities to enhance the skin penetration depth of pharmacological agents. This article reviews recent advances in the development of various strategies for skin penetration enhancement. We show that approaches such as ultrasound waves, laser, and microneedle patches have successfully been employed to physically disrupt the stratum corneum structure for enhanced transdermal delivery. Rather than physical approaches, several non-physical route have also been utilized for efficient transdermal delivery across the skin barrier. Finally, we discuss some clinical applications of transdermal delivery systems for gene and drug delivery. This paper shows that transdermal delivery devices can potentially function for diverse healthcare and medical applications while further investigations are still necessary for more efficient skin penetration of gene and drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Polymeric Films Loaded with Vitamin E and Aloe vera for Topical Application in the Treatment of Burn Wounds

PubMed Central

Pereira, Gabriela Garrastazu; Guterres, Sílvia Stanisçuaki; Balducci, Anna Giulia; Colombo, Paolo

2014-01-01

Burns are serious traumas related to skin damage, causing extreme pain and possibly death. Natural drugs such as Aloe vera and vitamin E have been demonstrated to be beneficial in formulations for wound healing. The aim of this work is to develop and evaluate polymeric films containing Aloe vera and vitamin E to treat wounds caused by burns. Polymeric films containing different quantities of sodium alginate and polyvinyl alcohol (PVA) were characterized for their mechanical properties and drug release. The polymeric films, which were produced, were thin, flexible, resistant, and suitable for application on damaged skin, such as in burn wounds. Around 30% of vitamin E acetate was released from the polymeric films within 12 hours. The in vivo experiments with tape stripping indicated an effective accumulation in the stratum corneum when compared to a commercial cream containing the same quantity of vitamin E acetate. Vitamin E acetate was found in higher quantities in the deep layers of the stratum corneum when the film formulation was applied. The results obtained show that the bioadhesive films containing vitamin E acetate and Aloe vera could be an innovative therapeutic system for the treatment of burns. PMID:24524083

Transdermal transport pathway creation: Electroporation pulse order.

PubMed

Becker, Sid; Zorec, Barbara; Miklavčič, Damijan; Pavšelj, Nataša

2014-11-01

In this study we consider the physics underlying electroporation which is administered to skin in order to radically increase transdermal drug delivery. The method involves the application of intense electric fields to alter the structure of the impermeable outer layer, the stratum corneum. A generally held view in the field of skin electroporation is that the skin's drop in resistance (to transport) is proportional to the total power of the pulses (which may be inferred by the number of pulses administered). Contrary to this belief, experiments conducted in this study show that the application of high voltage pulses prior to the application of low voltage pulses result in lower transport than when low voltage pulses alone are applied (when less total pulse power is administered). In order to reconcile these unexpected experimental results, a computational model is used to conduct an analysis which shows that the high density distribution of very small aqueous pathways through the stratum corneum associated with high voltage pulses is detrimental to the evolution of larger pathways that are associated with low voltage pulses. Copyright © 2014 Elsevier Inc. All rights reserved.

Novel drug delivery strategies for porphyrins and porphyrin precursors

NASA Astrophysics Data System (ADS)

Morrow, D. I. J.; Donnelly, R. F.

2009-06-01

superficial lesions, such as actinic keratosis. In addition, photodynamic antimicrobial chemotherapy (PACT) is attracting increasing interest for the treatment of infection. However, delivery strategies for topical PDT and PACT are still based on application of rather simplistic cream and solution formulations, with little consideration given to thermodynamics, targeting or the physicochemical properties of the active agent. Purpose-designed dosage forms for topical delivery of aminolevulinic acid or its esters include creams containing penetration enhancers and/or iron chelators, pressure sensitive patches and bioadhesive patches. Such systems aim to enhance drug delivery across the stratum corneum and keratinised debris overlying neoplastic lesions and improve subsequent protoporphyrin IX (PpIX) production. The alternative to using porphyrin precursors is the use of pre-formed photosensitisers. However, owing to their relatively high molecular weights, conventional topical application is not appropriate. Innovative strategies, such as the use of needle-free injections and microneedle arrays, bypass the stratum corneum, enabling rapid and targeted delivery not only porphyrin precursors but also pre-formed photosensitisers. This presentation will review drug delivery work published to date in the fields of PDT and PACT. In addition, the benefits of employing the latest advances in pharmaceutical technology will be highlighted.

Development of biodegradable hyperbranched core-multishell nanocarriers for efficient topical drug delivery.

PubMed

Du, Fang; Hönzke, Stefan; Neumann, Falko; Keilitz, Juliane; Chen, Wei; Ma, Nan; Hedtrich, Sarah; Haag, Rainer

2016-11-28

The topical application of drugs allows for a local application in skin disease and can reduce side effects. Here we present biodegradable core-multishell (CMS) nanocarriers which are composed of a hyperbranched polyglycerol core functionalized with diblock copolymers consisting of polycaprolactone (PCL) and poly(ethylene glycol) (mPEG) as the outer shell. The anti-inflammatory drug Dexamethasone (Dexa) was loaded into these CMS nanocarriers. DLS results suggested that Dexa loaded nanoparticles mostly act as a unimolecular carrier system. With longer PCL segments, a better transport capacity is observed. In vitro skin permeation studies showed that CMS nanocarriers could improve the Nile red penetration through the skin by up to 7 times, compared to a conventional cream formulation. Interestingly, covalently FITC-labeled CMS nanocarriers remain in the stratum corneum layer. This suggests the enhancement is due to the release of cargo after being transported into the stratum corneum by the CMS nanocarriers. In addition, the hPG-PCL-mPEG CMS nanocarriers exhibited good stability, low cytotoxicity, and their production can easily be scaled up, which makes them promising nanocarriers for topical drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

Rapid fabrication method of a microneedle mold with controllable needle height and width.

PubMed

Lin, Yen-Heng; Lee, I-Chi; Hsu, Wei-Chieh; Hsu, Ching-Hong; Chang, Kai-Ping; Gao, Shao-Syuan

2016-10-01

The main issue of transdermal drug delivery is that macromolecular drugs cannot diffuse through the stratum corneum of skin. Many studies have pursued micro-sized needles encapsulated with drugs to overcome this problem, as these needles can pierce the stratum corneum and allow drugs to enter the circulatory system of the human body. However, most microneedle fabrication processes are time-consuming and require expensive equipment. In this study, we demonstrate a rapid method for fabricating a microneedle mold using drawing lithography and a UV-cured resin. The mold was filled with a water-soluble material, polyvinylpyrrolidone (PVP), which was then demolded to produce a water-soluble microneedle array. The results of an in vitro skin insertion test using PVP microneedles and pig ear skin demonstrated the feasibility of the microneedle mold. In addition, by controlling the viscosity of the UV-cured resin through various heat treatments, microneedles with different heights and aspect ratios were produced. Compared with other methods, this technology significantly simplifies and accelerates the mold fabrication process. In addition, the required equipment is relatively simple and inexpensive. Through this technology, we can rapidly fabricate microneedle molds with controllable dimensions for various applications.

Absorption of ethanol, acetone, benzene and 1,2-dichloroethane through human skin in vitro: a test of diffusion model predictions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gajjar, Rachna M.; Kasting, Gerald B., E-mail: Gerald.Kasting@uc.edu

The overall goal of this research was to further develop and improve an existing skin diffusion model by experimentally confirming the predicted absorption rates of topically-applied volatile organic compounds (VOCs) based on their physicochemical properties, the skin surface temperature, and the wind velocity. In vitro human skin permeation of two hydrophilic solvents (acetone and ethanol) and two lipophilic solvents (benzene and 1,2-dichloroethane) was studied in Franz cells placed in a fume hood. Four doses of each {sup 14}C-radiolabed compound were tested — 5, 10, 20, and 40 μL cm{sup −2}, corresponding to specific doses ranging in mass from 5.0 tomore » 63 mg cm{sup −2}. The maximum percentage of radiolabel absorbed into the receptor solutions for all test conditions was 0.3%. Although the absolute absorption of each solvent increased with dose, percentage absorption decreased. This decrease was consistent with the concept of a stratum corneum deposition region, which traps small amounts of solvent in the upper skin layers, decreasing the evaporation rate. The diffusion model satisfactorily described the cumulative absorption of ethanol; however, values for the other VOCs were underpredicted in a manner related to their ability to disrupt or solubilize skin lipids. In order to more closely describe the permeation data, significant increases in the stratum corneum/water partition coefficients, K{sub sc}, and modest changes to the diffusion coefficients, D{sub sc}, were required. The analysis provided strong evidence for both skin swelling and barrier disruption by VOCs, even by the minute amounts absorbed under these in vitro test conditions. - Highlights: • Human skin absorption of small doses of VOCs was measured in vitro in a fume hood. • The VOCs tested were ethanol, acetone, benzene and 1,2-dichloroethane. • Fraction of dose absorbed for all compounds at all doses tested was less than 0.3%. • The more aggressive VOCs absorbed at higher

Development of a Rat Model to Investigate Contributions of Anatomic and Physiologic Determinants of in Vivo Skin Permeation

DTIC Science & Technology

1991-08-30

physiologic states. Physiologic perturbations were performed to test the sensitivity of the model system to detect effects of minoxidil -mediated... Minoxidil , leukotriene D̂ , tape stripping of stratum corneum, and topical ether-ethanol experiments produced statistically significant increases (52 to... Minoxidil 68 B. Phenylephrine 69 C. Leukotriene D̂ 69 D. Ether-Ethanol 70 E. Tape stripping 76 8. Data analysis 77 Vlll RESULTS 80 1

Lack of Effect of 94 GHz Radio Frequency Radiation Exposure in an Animal Model of Skin Carcinogenesis

DTIC Science & Technology

2001-10-01

villous or arborescent outgrowths of fibrovascular stroma covered by neoplastic cells; although benign, papillomas are premalignant lesions that will...thin stratum corneum; 1, minimal hyperplasia , epithelium ~4–6 cell layers thick; 2, minimal to mild hyperplasia , variable amounts of hyperplasia ...across the specimen, areas fitting each description present; 3, mild hyperplasia , epithelium ~7–9 cell layers thick or epithelial layer composed of ~4–6

Effect of soaps and detergents on epidermal barrier function.

PubMed

Wolf, Ronni; Parish, Lawrence Charles

2012-01-01

The past decade has witnessed an explosion of new impartial information about the complex interaction of the skin with topically applied substances, including soaps and detergents. Despite of all these new data, our knowledge on the exact pathomechanism and molecular events leading to detergent-induced barrier dysfunction remains incomplete and the answers continue to elude us. The longtime prevailing opinion which contends that the damaging effect of soaps and detergents is related to their property to extract and remove useful intercellular lipids has mostly been abandoned. Although this effect might be involved in the damaging effect, it is definitely not the sole mechanism, nor, indeed, is it even the main one. Skin proteins damage, the interaction with keratins and their denaturation, swelling of cell membranes and collagen fibers, cytotoxicity expressed with cellular lysis are other important mechanisms. One proposed mechanism is that an initial stratum corneum hyper-hydration results from a continuous disruption of the secondary and tertiary structures of keratin protein by surfactants, exposing new water-binding sites, thereby increasing the hydration of the membrane. Following evaporation of excess water, the denatured keratin possesses a decreased water-binding capacity and decreased ability to function as a barrier. Recent studies have also emphasized the effects of detergents on lipid synthesis, on lipid-metabolizing enzymes and on keratinocyte differentiation. Copyright © 2012 Elsevier Inc. All rights reserved.

Novel hydrogel-based preparation-free EEG electrode.

PubMed

Alba, Nicolas Alexander; Sclabassi, Robert J; Sun, Mingui; Cui, Xinyan Tracy

2010-08-01

The largest obstacles to signal transduction for electroencephalography (EEG) recording are the hair and the epidermal stratum corneum of the skin. In typical clinical situations, hair is parted or removed, and the stratum corneum is either abraded or punctured using invasive penetration devices. These steps increase preparation time, discomfort, and the risk of infection. Cross-linked sodium polyacrylate gel swelled with electrolyte was explored as a possible skin contact element for a prototype preparation-free EEG electrode. As a superabsorbent hydrogel, polyacrylate can swell with electrolyte solution to a degree far beyond typical contemporary electrode materials, delivering a strong hydrating effect to the skin surface. This hydrating power allows the material to increase the effective skin contact surface area through wetting, and noninvasively decrease or bypass the highly resistive barrier of the stratum corneum, allowing for reduced impedance and improved electrode performance. For the purposes of the tests performed in this study, the polyacrylate was prepared both as a solid elastic gel and as a flowable paste designed to penetrate dense scalp hair. The gel can hold 99.2% DI water or 91% electrolyte solution, and the water content remains high after 29 h of air exposure. The electrical impedance of the gel electrode on unprepared human forearm is significantly lower than a number of commercial ECG and EEG electrodes. This low impedance was maintained for at least 8 h (the longest time period measured). When a paste form of the electrode was applied directly onto scalp hair, the impedance was found to be lower than that measured with commercially available EEG paste applied in the same manner. Time-frequency transformation analysis of frontal lobe EEG recordings indicated comparable frequency response between the polyacrylate-based electrode on unprepared skin and the commercial EEG electrode on abraded skin. Evoked potential recordings demonstrated

Effects of adenosine 5'-monophosphate on epidermal turnover.

PubMed

Furukawa, Fukumi; Kanehara, Shoko; Harano, Fumiki; Shinohara, Shigeo; Kamimura, Junko; Kawabata, Shigekatsu; Igarashi, Sachiyo; Kawamura, Mitsuaki; Yamamoto, Yuki; Miyachi, Yoshiki

2008-10-01

The structure and function of the epidermis is maintained by cell renewal based on epidermal turnover. Epidermal turnover is delayed by aging, and it is thought that the delay of the epidermal turnover is a cause of aging alternation of skin. The epidermal turnover is related to the energy metabolism of epidermal basal cells. Adenosine 5'-triphosphate (ATP) is needed for cell renewal: cell division, and adenosine 5'-monophosphate (AMP) increases the amount of intracellular ATP. These findings suggest that AMP accelerates the epidermal turnover delayed by aging. This study investigated whether AMP and adenosine 5'-monophosphate disodium salt (AMP2Na) accelerates the epidermal turnover. An effect of AMP2Na on cell proliferation was examined by our counting of keratinocytes. An effect of AMP2Na on cell cycle was examined by our counting of basal cells in DNA synthetic period of hairless rats. The effects of AMP2Na (or AMP) on the epidermal turnover were examined by our measuring stratum corneum transit time by use of guinea pigs, and by our measuring stratum corneum surface area by use of hairless rats and in a clinical pharmacological study. The AMP2Na showed two different profiles on the proliferation of primary cultured keratinocytes. At a low concentration it induced cell growth, whereas at a high concentration it inhibited cell growth. The number of basal cells in the DNA synthetic period of AMP2Na was significantly higher than that of the vehicle in hairless rats. The stratum corneum transit time of AMP2Na was significantly shorter than that of the vehicle in guinea pigs. The corneocyte surface area of emulsion containing AMP2Na was significantly smaller than that of the vehicle in volunteers. We conclude that AMP promotes the cell proliferation and the cell cycle progression of epidermal basal cells and accelerates epidermal turnover safely. In addition, AMP is useful for skin rejuvenation in dermatology and aesthetic dermatology.

Effects of a Skin Barrier Cream on Management of Incontinence-Associated Dermatitis in Older Women: A Cluster Randomized Controlled Trial.

PubMed

Kon, Yuka; Ichikawa-Shigeta, Yoshie; Iuchi, Terumi; Nakajima, Yukari; Nakagami, Gojiro; Tabata, Keiko; Sanada, Hiromi; Sugama, Junko

The purpose of this study was to examine the effects of a skin barrier cream with moisturization and skin-protectant characteristics for improving the severity of incontinence-associated dermatitis (IAD) pertaining to the skin physiology and appearance. We measured the following outcomes: (1) skin physiological characteristics indicating skin protection and enhancement of the skin's moisture barrier (stratum corneum hydration, dermis hydration level, transepidermal water loss, and skin pH); and (2) changes in skin appearance (the degree of erythema and pigmentation, and the sulcus cutis condition). Single-blind, cluster randomized controlled trial. The study was conducted in a long-term care facility in Japan between November 7, 2011, and May 6, 2012. We used block randomization to obtain a random sample of 6 (4 experimental and 2 control) out of 10 available wards. All subjects were elderly women with IAD of the buttock or inner thigh. We assessed 295 patients, but only 33 met inclusion criteria; 18 were allocated to the experimental group and 15 were allocated to the control group. All participants were managed with cleansing with a skin cleanser and application of a moisturizer daily. In addition, a skin barrier cream designed to enhance the skin's moisture barrier and act as a protective barrier was applied to the skin of patients in the experimental group 3 times a day when absorptive briefs were changed. Skin physiological and appearance characteristics were scored only at the buttock or thigh area. All data were collected on days 1 and 14 of the study. Univariate analysis found that the erythema index was lower in the intervention group than in the control group at day 14 (P = .004). Multivariate analysis found significant associations between use of the skin barrier cream and increased stratum corneum hydration (β= .443, P = .031), decreased skin pH (β=-.439, P = .020), and magnitude of erythema (β=-.451, P = .018). Study findings suggest that a barrier

Stratum corneum integrity as a predictor for peristomal skin problems in ostomates.

PubMed

Nybaek, H; Lophagen, S; Karlsmark, T; Bang Knudsen, D; Jemec, G B E

2010-02-01

Peristomal skin problems are common, most often the result is disruption of the skin barrier and this may account for more than one in three visits to ostomy nurses. Therefore a specific assessment of individual risk factors relating to the skin barrier function would be of great interest. Skin barrier integrity in ostomy patients with peristomal skin problems (PSP) was compared with that of ostomy patients with normal skin (controls) using transepidermal water loss (TEWL). Mechanical barrier disruption was determined by a tape stripping test and chemical barrier disruption [sodium lauryl sulphate (SLS) 0.25%]. Patients and controls had a highly significant increase in TEWL value in the peristomal area compared with nonperistomal contralateral abdominal skin (P < 0.0001 for both groups). The skin barrier of normal-looking contralateral skin of ostomates was found to be borderline impaired in patients with PSP compared with those without. A linear association was seen between the number of tape strips removed and TEWL for both cases and controls. Tape stripping suggested that patients with PSP had less resilient skin (P = 0.002). A significant difference in TEWL value between cases and controls was also seen for the SLS patch test on the dorsal skin (P = 0.02). Successive tape stripping, a situation analogous to the normal use of a pouching system, caused a higher degree of barrier damage more rapidly in patients with PSP, indicating an impaired mechanical quality of the barrier. The SLS exposure test suggested a generally increased susceptibility to irritant dermatitis as assessed by TEWL. Our findings suggest tape stripping and SLS testing may have a role as predictive tests to identify patients at risk of PSP.

Emotional intelligence is a second-stratum factor of intelligence: evidence from hierarchical and bifactor models.

PubMed

MacCann, Carolyn; Joseph, Dana L; Newman, Daniel A; Roberts, Richard D

2014-04-01

This article examines the status of emotional intelligence (EI) within the structure of human cognitive abilities. To evaluate whether EI is a 2nd-stratum factor of intelligence, data were fit to a series of structural models involving 3 indicators each for fluid intelligence, crystallized intelligence, quantitative reasoning, visual processing, and broad retrieval ability, as well as 2 indicators each for emotion perception, emotion understanding, and emotion management. Unidimensional, multidimensional, hierarchical, and bifactor solutions were estimated in a sample of 688 college and community college students. Results suggest adequate fit for 2 models: (a) an oblique 8-factor model (with 5 traditional cognitive ability factors and 3 EI factors) and (b) a hierarchical solution (with cognitive g at the highest level and EI representing a 2nd-stratum factor that loads onto g at λ = .80). The acceptable relative fit of the hierarchical model confirms the notion that EI is a group factor of cognitive ability, marking the expression of intelligence in the emotion domain. The discussion proposes a possible expansion of Cattell-Horn-Carroll theory to include EI as a 2nd-stratum factor of similar standing to factors such as fluid intelligence and visual processing.

Which Stratum of Urban Elderly Is Most Vulnerable for Dementia?

PubMed Central

2016-01-01

Many factors associated with a patient's lifestyle may disrupt timely access to dementia diagnosis and management. The aim of this study was to compare characteristics of lifestyle factors at the time of initial evaluation for dementia across degrees of dementia, and to identify risk factors relating to late detection of dementia, in order to understand the various lifestyle barriers to timely recognition of the disease. We reviewed medical records of 1,409 subjects who were diagnosed as dementia among 35,723 inhabitants of Gwangjin-gu. Dementia severity was divided into three degrees. Age, sex, education, income, smoking, heavy drinking, physical activity, religion, and living conditions were evaluated. There was a significantly greater proportion of individuals who were old age, female, less educated, who had never smoked or drank heavily, without physical activity, with no religious activity and living with family other than spouse in the severe dementia group. The lifestyle risks of late detection were old age, lower education, less social interactions, less physical activity or living with family. We can define this group of patients as the vulnerable stratum to dementia evaluation. Health policy or community health services might find ways to better engage patients in this vulnerable stratum to dementia. PMID:27550494

Skin penetration of silicon dioxide microneedle arrays.

PubMed

Kim, Sangchae; Shetty, S; Price, D; Bhansali, S

2006-01-01

Out-of-plane hollow silicon dioxide microneedle arrays were fabricated and investigated to determine their efficacy for transdermal applications. The fabrication process of the SiO2 microneedles is described, and mechanical fracture forces were investigated on microneedles with different geometrical dimensions. Biomechanical characterization of the microneedles was performed to specifically test for reliable stratum corneum and skin insertion by changing the regulatory parameters such as needle width and cross-section.

White piedra, black piedra, tinea versicolor, and tinea nigra: contribution to the diagnosis of superficial mycosis.

PubMed

Veasey, John Verrinder; Avila, Ricardo Bertozzi de; Miguel, Barbara Arruda Fraletti; Muramatu, Laura Hitomi

2017-01-01

Superficial mycoses are fungal infections restricted to the stratum corneum and to the hair shafts, with no penetration in the epidermis; they are: white piedra, black piedra, tinea versicolor, and tinea nigra. This study presents images of mycological tests performed in the laboratory, as well as exams performed at the authors office, in order to improve the dermatologist's knowledge about the diagnosis of these dermatoses, which are common in many countries.

Progress in the use of microemulsions for transdermal and dermal drug delivery.

PubMed

Ita, Kevin

2017-06-01

Transdermal drug delivery continues to attract considerable interest in the scientific community. However, due to the hindrance provided by the stratum corneum, it is not possible to deliver most medications in therapeutically significant amounts. One of the ways of increasing the penetration of drugs across the skin is through the use of microemulsions (MEs). This review focuses on the role of MEs in enhancing topical and transdermal drug delivery.

Impacts of chemical enhancers on skin permeation and deposition of terbinafine.

PubMed

Erdal, Meryem Sedef; Peköz, Ayca Yıldız; Aksu, Buket; Araman, Ahmet

2014-08-01

The addition of chemical enhancers into formulations is the most commonly employed approach to overcome the skin barrier. The objective of this work was to evaluate the effect of vehicle and chemical enhancers on the skin permeation and accumulation of terbinafine, an allylamine antifungal drug. Terbinafine (1% w/w) was formulated as a Carbopol 934 P gel formulation in presence and absence of three chemical enhancers, nerolidol, dl-limonene and urea. Terbinafine distribution and deposition in stratum corneum (SC) and skin following 8-h ex vivo permeation study was determined using a sequential tape stripping procedure. The conformational order of SC lipids was investigated by ATR-FTIR spectroscopy. Nerolidol containing gel formulation produced significantly higher enhancement in terbinafine permeation through skin and its skin accumulation was increased. ATR-FTIR results showed enhancer induced lipid bilayer disruption in SC. Urea resulted in enhanced permeation of terbinafine across the skin and a balanced distribution to the SC was achieved. But, dl-limonene could not minimize the accumulation of terbinafine in the upper SC. Nerolidol dramatically improved the skin permeation and deposition of terbinafine in the skin that might help to optimize targeting of the drug to the epidermal sites as required for both of superficial and deep cutaneous fungal infections.

Hydration Effects on Skin Microstructure as Probed by High-Resolution Cryo-Scanning Electron Microscopy and Mechanistic Implications to Enhanced Transcutaneous Delivery of Biomacromolecules

PubMed Central

Tan, Grace; Xu, Peng; Lawson, Louise B.; He, Jibao; Freytag, Lucia C.; Clements, John D.; John, Vijay T.

2010-01-01

Although hydration is long known to improve the permeability of skin, penetration of macromolecules such as proteins is limited and the understanding of enhanced transport is based on empirical observations. This study uses high-resolution cryo-scanning electron microscopy to visualize microstructural changes in the stratum corneum (SC) and enable a mechanistic interpretation of biomacromolecule penetration through highly hydrated porcine skin. Swollen corneocytes, separation of lipid bilayers in the SC intercellular space to form cisternae, and networks of spherical particulates are observed in porcine skin tissue hydrated for a period of 4–10 h. This is explained through compaction of skin lipids when hydrated, a reversal in the conformational transition from unilamellar liposomes in lamellar granules to lamellae between keratinocytes when the SC skin barrier is initially established. Confocal microscopy studies show distinct enhancement in penetration of fluorescein isothiocyanate-bovine serum albumin (FITC-BSA) through skin hydrated for 4–10 h, and limited penetration of FITC-BSA once skin is restored to its natively hydrated structure when exposed to the environment for 2–3 h. These results demonstrate the effectiveness of a 4–10 h hydration period to enhance transcutaneous penetration of large biomacromolecules without permanently damaging the skin. PMID:19582754

Raman spectroscopic analysis of human skin tissue sections ex-vivo: evaluation of the effects of tissue processing and dewaxing

NASA Astrophysics Data System (ADS)

Ali, Syed M.; Bonnier, Franck; Tfayli, Ali; Lambkin, Helen; Flynn, Kathleen; McDonagh, Vincent; Healy, Claragh; Clive Lee, T.; Lyng, Fiona M.; Byrne, Hugh J.

2013-06-01

Raman spectroscopy coupled with K-means clustering analysis (KMCA) is employed to elucidate the biochemical structure of human skin tissue sections and the effects of tissue processing. Both hand and thigh sections of human cadavers were analyzed in their unprocessed and formalin-fixed, paraffin-processed (FFPP), and subsequently dewaxed forms. In unprocessed sections, KMCA reveals clear differentiation of the stratum corneum (SC), intermediate underlying epithelium, and dermal layers for sections from both anatomical sites. The SC is seen to be relatively rich in lipidic content; the spectrum of the subjacent layers is strongly influenced by the presence of melanin, while that of the dermis is dominated by the characteristics of collagen. For a given anatomical site, little difference in layer structure and biochemistry is observed between samples from different cadavers. However, the hand and thigh sections are consistently differentiated for all cadavers, largely based on lipidic profiles. In dewaxed FFPP samples, while the SC, intermediate, and dermal layers are clearly differentiated by KMCA of Raman maps of tissue sections, the lipidic contributions to the spectra are significantly reduced, with the result that respective skin layers from different anatomical sites become indistinguishable. While efficient at removing the fixing wax, the tissue processing also efficiently removes the structurally similar lipidic components of the skin layers. In studies of dermatological processes in which lipids play an important role, such as wound healing, dewaxed samples are therefore not appropriate. Removal of the lipids does however accentuate the spectral features of the cellular and protein components, which may be more appropriate for retrospective analysis of disease progression and biochemical analysis using tissue banks.

In Vivo Multiphoton Microscopy for Investigating Biomechanical Properties of Human Skin.

PubMed

Liang, Xing; Graf, Benedikt W; Boppart, Stephen A

2011-06-01

The biomechanical properties of living cells depend on their molecular building blocks, and are important for maintaining structure and function in cells, the extracellular matrix, and tissues. These biomechanical properties and forces also shape and modify the cellular and extracellular structures under stress. While many studies have investigated the biomechanics of single cells or small populations of cells in culture, or the properties of organs and tissues, few studies have investigated the biomechanics of complex cell populations in vivo. With the use of advanced multiphoton microscopy to visualize in vivo cell populations in human skin, the biomechanical properties are investigated in a depth-dependent manner in the stratum corneum and epidermis using quasi-static mechanical deformations. A 2D elastic registration algorithm was used to analyze the images before and after deformation to determine displacements in different skin layers. In this feasibility study, the images and results from one human subject demonstrate the potential of the technique for revealing differences in elastic properties between the stratum corneum and the rest of the epidermis. This interrogational imaging methodology has the potential to enable a wide range of investigations for understanding how the biomechanical properties of in vivo cell populations influence function in health and disease.

Investigation of the piezoelectric thimble tactile device operating modes.

PubMed

Bansevicius, Ramutis; Dragasius, Egidijus; Grigas, Vytautas; Jurenas, Vytautas; Mazeika, Darius; Zvironas, Arunas

2014-01-01

A multifunctional device to transfer graphical or text information for blind or visually impaired is presented. The prototype using tactile perception has been designed where information displayed on the screen of electronic device (mobile phone, PC) is transferred by oscillating needle, touching the fingertip. Having the aim to define optimal parameters of the fingertip excitation by needle, the computational analysis of different excitation modes has been carried out. A 3D solid computational finite element model of the skin segment, comprising four main fingertip skin layers (stratum corneum, epidermis, dermis and hypodermis) was built by using ANSYS Workbench FEA software. Harmonic analysis of its stress-strain state under excitation with different frequency (up to 10000 Hz) and harmonic force (0.01 N), acting outer stratum corneum layer in normal direction at one, two or three points has been performed. The influence of the mode of dynamic loading of skin was evaluated (in terms of the tactile signal level) on the basis of the normal and shear elastic strain in dermis, where mechanoreceptors are placed. It is shown that the tactile perception of information, delivered by three vibrating pins, may be influenced by configuration of excitation points (their number and phase of loading) and the frequency of excitation.

Usefulness and pharmacokinetic study of oral terbinafine for hyperkeratotic type tinea pedis.

PubMed

Kikuchi, Izumi; Tanuma, Hiroyuki; Morimoto, Kensuke; Kawana, Seiji

2008-01-01

To study and establish an optimal administration method of oral antifungal, terbinafine (TBF), for hyperkeratotic type tinea pedis, from the pharmacokinetic point of view, 20 patients with hyperkeratotic type tinea pedis were given TBF 125 mg once daily for 4 weeks and observed over time for improvement in dermatological symptoms and mycological efficacy. Targeting five of the patients, TBF concentration in the stratum corneum was measured using the liquid chromatography/tandem mass spectrometry (LC-MS/MS) method. TBF was detected in the stratum corneum of the sole 1 week after beginning the treatment in some cases and reached its peak 1 week after the completion of the treatment with a concentration of 247.8 ng g(-1), which was approximately more than 50 times higher than its minimal inhibitory concentration against dermatophytes. TBF was not detected at 8 weeks post-treatment, although its concentration was 50.73 ng g(-1) at 6 weeks post-treatment. Its effectiveness rate (effective + markedly effective) was 95% (19/20) with no adverse reactions, including abnormal changes in the laboratory test values, in any patient. These results suggest that TBF is a useful drug to treat hyperkeratotic tinea pedis from the pharmacokinetic point of view.

In vivo skin effects of a dimethylaminoethanol (DMAE) based formulation.

PubMed

Tadini, K A; Campos, P M B G Maia

2009-12-01

Dimethylaminoethanol (DMAE) has been used in anti-aging formulations but few scientifically based data address its efficacy. The aim of this study was to evaluate the effects of DMAE-based formulations on hairless mice and human skin. Formulations containing with or without DMAE were applied to the dorsum of hairless mice. Histopathological and histometric evaluations were carried out after seven days. Formulations were also applied to the ventral forearm and the lateral periocular area of human volunteers. Stratum corneum water content and skin mechanical properties were analyzed using Corneometer and Cutometer, before and after a single and repeated application. Histometric evaluations showed that formulations with or without DMAE increased the viable epidermis thickness, but only the DMAE-supplemented formulation led to increased dermal thickness. DMAE also induced increase in collagen fiber thickness, which was observed in the histopathological study. After the single and the 8-week period application on human skin, formulations with and without DMAE enhanced the stratum corneum water content in the forearm skin. Mechanical properties were not significantly modified. So, we can suggest that DMAE action is related to its effects on the dermis as observed in the histopathological and histometric studies and showed hydration effects on skin.

Evaluation of psychological stress in confined environments using salivary, skin, and facial image parameters.

PubMed

Egawa, Mariko; Haze, Shinichiro; Gozu, Yoko; Hosoi, Junichi; Onodera, Tomoko; Tojo, Yosuke; Katsuyama, Masako; Hara, Yusuke; Katagiri, Chika; Inoue, Natsuhiko; Furukawa, Satoshi; Suzuki, Go

2018-05-29

Detecting the influence of psychological stress is particularly important in prolonged space missions. In this study, we determined potential markers of psychological stress in a confined environment. We examined 23 Japanese subjects staying for 2 weeks in a confined facility at Tsukuba Space Center, measuring salivary, skin, and facial image parameters. Saliva was collected at four points in a single day to detect diurnal variation. Increases in salivary cortisol were detected after waking up on the 4th and 11th days, and at 15:30 on the 1st and in the second half of the stay. Transepidermal water loss (TEWL) and sebum content of the skin were higher compared with outside the facility on the 4th and 1st days respectively. Increased IL-1β in the stripped stratum corneum was observed on the 14th day, and 7 days after leaving. Differences in facial expression symmetry at the time of facial expression changes were observed on 11th and 14th days. Thus, we detected a transition of psychological stress using salivary cortisol profiles and skin physiological parameters. The results also suggested that IL-1β in the stripped stratum corneum and facial expression symmetry are possible novel markers for conveniently detecting psychological stress.

High resolution in-vivo imaging of skin with full field optical coherence tomography

NASA Astrophysics Data System (ADS)

Dalimier, E.; Bruhat, Alexis; Grieve, K.; Harms, F.; Martins, F.; Boccara, C.

2014-03-01

Full-field OCT (FFOCT) has the ability to provide en-face images with a very good axial sectioning as well as a very high transverse resolution (about 1 microns in all directions). Therefore it offers the possibility to visualize biological tissues with very high resolution both on the axial native view, and on vertical reconstructed sections. Here we investigated the potential dermatological applications of in-vivo skin imaging with FFOCT. A commercial FFOCT device was adapted for the in-vivo acquisition of stacks of images on the arm, hand and finger. Several subjects of different benign and pathological skin conditions were tested. The images allowed measurement of the stratum corneum and epidermis thicknesses, measurement of the stratum corneum refractive index, size measurement and count of the keratinocytes, visualization of the dermal-epidermal junction, and visualization of the melanin granules and of the melanocytes. Skins with different pigmentations could be discriminated and skin pathologies such as eczema could be identified. The very high resolution offered by FFOCT both on axial native images and vertical reconstructed sections allows for the visualization and measurement of a set of parameters useful for cosmetology and dermatology. In particular, FFOCT is a potential tool for the understanding and monitoring of skin hydration and pigmentation, as well as skin inflammation.

Cellular responses to disruption of the permeability barrier in a three-dimensional organotypic epidermal model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ajani, Gati; Sato, Nobuyuki; Mack, Judith A.

2007-08-15

Repeated injury to the stratum corneum of mammalian skin (caused by friction, soaps, or organic solvents) elicits hyperkeratosis and epidermal thickening. Functionally, these changes serve to restore the cutaneous barrier and protect the organism. To better understand the molecular and cellular basis of this response, we have engineered an in vitro model of acetone-induced injury using organotypic epidermal cultures. Rat epidermal keratinocytes (REKs), grown on a collagen raft in the absence of any feeder fibroblasts, developed all the hallmarks of a true epidermis including a well-formed cornified layer. To induce barrier injury, REK cultures were treated with intermittent 30-s exposuresmore » to acetone then were fixed and paraffin-sectioned. After two exposures, increased proliferation (Ki67 and BrdU staining) was observed in basal and suprabasal layers. After three exposures, proliferation became confined to localized buds in the basal layer and increased terminal differentiation was observed (compact hyperkeratosis of the stratum corneum, elevated levels of K10 and filaggrin, and heightened transglutaminase activity). Thus, barrier disruption causes epidermal hyperplasia and/or enhances differentiation, depending upon the extent and duration of injury. Given that no fibroblasts are present in the model, the ability to mount a hyperplastic response to barrier injury is an inherent property of keratinocytes.« less

Swept-source optical coherence tomography of lower limb wound healing with histopathological correlation

NASA Astrophysics Data System (ADS)

Barui, Ananya; Banerjee, Provas; Patra, Rusha; Das, Raunak Kumar; Dhara, Santanu; Dutta, Pranab K.; Chatterjee, Jyotirmoy

2011-02-01

Direct noninvasive visualization of wound bed with depth information is important to understand the tissue repair. We correlate skin swept-source-optical coherence tomography (OCT) with histopathological and immunohistochemical evaluation on traumatic lower limb wounds under honey dressing to compare and assess the tissue repair features acquired noninvasively and invasively. Analysis of optical biopsy identifies an uppermost brighter band for stratum corneum with region specific thickness (p < 0.0001) and gray-level intensity (p < 0.0001) variation. Below the stratum corneum, variation in optical intensities is remarkable in different regions of the wound bed. Correlation between OCT and microscopic observations are explored especially in respect to progressive growth and maturation of the epithelial and subepithelial components. Characteristic transition of uniform hypolucid band in OCT image for depigmented zone to wavy highly lucid band in the pigmented zone could be directly correlated with the microscopic findings. The transformation of prematured epithelium of depigmented area, with low expression of E-cadherin, to matured epithelium with higher E-cadherin expression in pigmented zone, implicated plausible change in their optical properties as depicted in OCT. This correlated evaluation of multimodal images demonstrates applicability of swept-source-OCT in wound research and importance of integrated approach in validation of new technology.

Skin surface hydration decreases rapidly during long distance flights.

PubMed

Guéhenneux, Sabine; Gardinier, Sophie; Morizot, Frederique; Le Fur, Isabelle; Tschachler, Erwin

2012-05-01

Dehydration of the stratum corneum leads to sensations and symptoms of 'dry skin' such as skin tightness and itchiness. As these complaints are frequently experienced by airline travellers, the aim of this study was to investigate the changes in skin surface hydration during long distance flights. The study was performed on four healthy Caucasian, and on four Japanese women aged 29-39 years, travelling on long distance flights. They had stopped using skin care products at least 12 h before, and did not apply them during the flights. The air temperature and relative humidity inside the cabin, as well as skin capacitance of the face and forearm of participants, were registered at several time points before and during the flights. Relative humidity of the aircraft cabin dropped to levels below 10% within 2 h after take-off and stayed at this value throughout the flight. Skin capacitance decreased rapidly on both the face and forearms with most pronounced changes on the cheeks where it decreased by up to 37%. Our results demonstrate that during long distance flights, the aircraft cabin environment leads to a rapid decrease in stratum corneum hydration, an alteration, which probably accounts for the discomfort experienced by long distance aircraft travellers. © 2011 John Wiley & Sons A/S.

Why pens have rubbery grips

NASA Astrophysics Data System (ADS)

Dzidek, Brygida; Bochereau, Séréna; Johnson, Simon A.; Hayward, Vincent; Adams, Michael J.

2017-10-01

The process by which human fingers gives rise to stable contacts with smooth, hard objects is surprisingly slow. Using high-resolution imaging, we found that, when pressed against glass, the actual contact made by finger pad ridges evolved over time following a first-order kinetics relationship. This evolution was the result of a two-stage coalescence process of microscopic junctions made between the keratin of the stratum corneum of the skin and the glass surface. This process was driven by the secretion of moisture from the sweat glands, since increased hydration in stratum corneum causes it to become softer. Saturation was typically reached within 20 s of loading the contact, regardless of the initial moisture state of the finger and of the normal force applied. Hence, the gross contact area, frequently used as a benchmark quantity in grip and perceptual studies, is a poor reflection of the actual contact mechanics that take place between human fingers and smooth, impermeable surfaces. In contrast, the formation of a steady-state contact area is almost instantaneous if the counter surface is soft relative to keratin in a dry state. It is for this reason that elastomers are commonly used to coat grip surfaces.

A covalently cross-linked gel derived from the epidermis of the pilot whale Globicephala melas.

PubMed

Baum, C; Fleischer, L-G; Roessner, D; Meyer, W; Siebers, D

2002-01-01

The rheological properties of the stratum corneum of the pilot whale (Globicephala melas) were investigated with emphasis on their significance to the self-cleaning abilities of the skin surface smoothed by a jelly material enriched with various hydrolytic enzymes. The gel formation of the collected fluid was monitored by applying periodic-harmonic oscillating loads using a stress-controlled rheometer. In the mechanical spectrum of the gel, the plateau region of the storage modulus G' (<1200 Pa) and the loss modulus G" (>120 Pa) were independent of frequency (omega = 43.98 to 0.13 rad x s(-1), tau = 15 Pa, T = 20 degrees C), indicating high elastic performance of a covalently cross-linked viscoelastic solid. In addition, multi-angle laser light scattering experiments (MALLS) were performed to analyse the potential time-dependent changes in the weight-average molar mass of the samples. The observed increase showed that the gel formation is based on the assembly of covalently cross-linked aggregates. The viscoelastic properties and the shear resistance of the gel assure that the enzyme-containing jelly material smoothing the skin surface is not removed from the stratum corneum by shear regimes during dolphin jumping. The even skin surface is considered to be most important for the self-cleaning abilities of the dolphin skin against biofouling.

Establishment of an evaluation method to detect drug distribution in hair follicles.

PubMed

Abe, Akinari; Saito, Miyuki; Kadhum, Wesam R; Todo, Hiroaki; Sugibayashi, Kenji

2018-05-05

Development of an appropriate method to evaluate drug disposition or targeting ability in hair follicles (HFs) is urgently needed in order to develop useful pharmaceutical products with pharmacological effects in HFs. In the present study, a cyanoacrylate biopsy (CB) method was used to measure drug disposition in HFs using a model hydrophilic drug, caffeine (CAF), and a lipophilic drug, 4-butylresorcinol (BR), in excised porcine skin. As a result, the height of HF replicas and the recovery ratio decreased with an increase in the application times of the CB method. HF replicas with a length of approximately 175 µm were obtained using a single application of the CB method. Drug distribution in the HF was detected even 5 min after topical application regardless of the lipophilicity of the drugs, although no drug disposition was observed in the deeper layers of the stratum corneum at the same time (5 min). Furthermore, significantly higher amounts of BR were observed in the stratum corneum and HF, compared with those of CAF. These results suggested that the CB method could be useful to evaluate the safety and efficacy as well as the disposition of topically applied chemicals, especially for HF-targeting drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

Percutaneous absorption

PubMed Central

Brisson, Paul

1974-01-01

Clinical effectiveness of topically applied medications depends on the ability of the active ingredient to leave its vehicle and penetrate into the epidermis. The stratum corneum is that layer of the epidermis which functionally is the most important in limiting percutaneous absorption, showing the characteristics of a composite semipermeable membrane. A mathematical expression of transepidermal diffusion may be derived from Fick's Law of mass transport; factors altering the rate of diffusion are discussed. PMID:4597976

White piedra, black piedra, tinea versicolor, and tinea nigra: contribution to the diagnosis of superficial mycosis*

PubMed Central

Veasey, John Verrinder; de Avila, Ricardo Bertozzi; Miguel, Barbara Arruda Fraletti; Muramatu, Laura Hitomi

2017-01-01

Superficial mycoses are fungal infections restricted to the stratum corneum and to the hair shafts, with no penetration in the epidermis; they are: white piedra, black piedra, tinea versicolor, and tinea nigra. This study presents images of mycological tests performed in the laboratory, as well as exams performed at the authors office, in order to improve the dermatologist's knowledge about the diagnosis of these dermatoses, which are common in many countries. PMID:29186263

Surfactant sodium lauryl sulfate enhances skin vaccination: molecular characterization via a novel technique using ultrafiltration capillaries and mass spectrometric proteomics.

PubMed

Huang, Chun-Ming; Wang, Chao-Cheng; Kawai, Mikako; Barnes, Stephen; Elmets, Craig A

2006-03-01

The skin is a highly accessible organ and thus provides an attractive immune environment for cost-effective, simple, and needle-free delivery of vaccines and immunomodulators. In this study, we pretreated mouse skin with an anionic surfactant, sodium lauryl sulfate (SLS), for a short period of time (10 min) followed by epicutaneous vaccination with hen egg lysozyme antigen. We demonstrated for the first time that pretreatment of skin with surfactant SLS significantly enhances the production of antibody to hen egg lysozyme. Short term pretreatment with SLS disorganized the stratum corneum, extracted partial lamellar lipids, induced the maturation of Langerhans cells, and did not result in epidermis thickening. To reveal the mechanism underlying these changes, particularly at the molecular level, we used a novel proteomic technique using ultrafiltration capillaries and mass spectrometry to identify in vivo proteins/peptides secreted in the SLS-pretreated skin. Two secretory proteins, named as calcium-binding protein S100A9 and thymosin beta4, were identified by this novel technique. These two proteins thus may provide new insight into the enhancing effect of surfactants on skin vaccination.

Dynamic Visualization of Dendritic Cell-Antigen Interactions in the Skin Following Transcutaneous Immunization

PubMed Central

Rattanapak, Teerawan; Birchall, James C.; Young, Katherine; Kubo, Atsuko; Fujimori, Sayumi; Ishii, Masaru; Hook, Sarah

2014-01-01

Delivery of vaccines into the skin provides many advantages over traditional parenteral vaccination and is a promising approach due to the abundance of antigen presenting cells (APC) residing in the skin including Langerhans cells (LC) and dermal dendritic cells (DDC). However, the main obstacle for transcutaneous immunization (TCI) is the effective delivery of the vaccine through the stratum corneum (SC) barrier to the APC in the deeper skin layers. This study therefore utilized microneedles (MN) and a lipid-based colloidal delivery system (cubosomes) as a synergistic approach for the delivery of vaccines to APC in the skin. The process of vaccine uptake and recruitment by specific types of skin APC was investigated in real-time over 4 hours in B6.Cg-Tg (Itgax-EYFP) 1 Mnz/J mice by two-photon microscopy. Incorporation of the vaccine into a particulate delivery system and the use of MN preferentially increased vaccine antigen uptake by a highly motile subpopulation of skin APC known as CD207+ DC. No uptake of antigen or any response to immunisation by LC could be detected. PMID:24586830

A homozygous nonsense mutation in the gene for Tmem79, a component for the lamellar granule secretory system, produces spontaneous eczema in an experimental model of atopic dermatitis.

PubMed

Sasaki, Takashi; Shiohama, Aiko; Kubo, Akiharu; Kawasaki, Hiroshi; Ishida-Yamamoto, Akemi; Yamada, Taketo; Hachiya, Takayuki; Shimizu, Atsushi; Okano, Hideyuki; Kudoh, Jun; Amagai, Masayuki

2013-11-01

Flaky tail (ma/ma Flg(ft/ft)) mice have a frameshift mutation in the filaggrin (Flg(ft)) gene and are widely used as a model of human atopic dermatitis associated with FLG mutations. These mice possess another recessive hair mutation, matted (ma), and develop spontaneous dermatitis under specific pathogen-free conditions, whereas genetically engineered Flg(-/-) mice do not. We identified and characterized the gene responsible for the matted hair and dermatitis phenotype in flaky tail mice. We narrowed down the responsible region by backcrossing ma/ma mice with wild-type mice and identified the mutation using next-generation DNA sequencing. We attempted to rescue the matted phenotype by introducing the wild-type matted transgene. We characterized the responsible gene product by using whole-mount immunostaining of epidermal sheets. We demonstrated that ma, but not Flg(ft), was responsible for the dermatitis phenotype and corresponded to a Tmem79 gene nonsense mutation (c.840C>G, p.Y280*), which encoded a 5-transmembrane protein. Exogenous Tmem79 expression rescued the matted hair and dermatitis phenotype of Tmem79(ma/ma) mice. Tmem79 was mainly expressed in the trans-Golgi network in stratum granulosum cells in the epidermis in both mice and humans. The Tmem79(ma/ma) mutation impaired the lamellar granule secretory system, which resulted in altered stratum corneum formation and a subsequent spontaneous dermatitis phenotype. The Tmem79(ma/ma) mutation is responsible for the spontaneous dermatitis phenotype in matted mice, probably as a result of impaired lamellar granule secretory system and altered stratum corneum barrier function. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Bovine rumen epithelium undergoes rapid structural adaptations during grain-induced subacute ruminal acidosis.

PubMed

Steele, Michael A; Croom, Jim; Kahler, Melissa; AlZahal, Ousama; Hook, Sarah E; Plaizier, Kees; McBride, Brian W

2011-06-01

Alterations in rumen epithelial structure and function during grain-induced subacute ruminal acidosis (SARA) are largely undescribed. In this study, four mature nonlactating dairy cattle were transitioned from a high-forage diet (HF; 0% grain) to a high-grain diet (HG; 65% grain). After feeding the HG diet for 3 wk, the cattle were transitioned back to the original HF diet, which was fed for an additional 3 wk. Continuous ruminal pH was measured on a weekly basis, and rumen papillae were biopsied during the baseline and at the first and final week of each diet. The mean, minimum, and maximum daily ruminal pH were depressed (P < 0.01) in the HG period compared with the HF period. During the HG period, SARA was diagnosed only during week 1, indicating ruminal adaptation to the HG diet. Microscopic examination of the papillae revealed a reduction (P < 0.01) in the stratum basale, spinosum, and granulosum layers, as well as total depth of the epithelium during the HG period. The highest (P < 0.05) papillae lesion scores were noted during week 1 when SARA occurred. Biopsied papillae exhibited a decline in cellular junctions, extensive sloughing of the stratum corneum, and the appearance of undifferentiated cells near the stratum corneum. Differential mRNA expression of candidate genes, including desmoglein 1 and IGF binding proteins 3, 5, and 6, was detected between diets using qRT-PCR. These results suggest that the structural integrity of the rumen epithelium is compromised during grain feeding and is associated with the differential expression of genes involved in epithelial growth and structure.

Investigations of percutaneous uptake of ultrafine TiO 2 particles at the high energy ion nanoprobe LIPSION

NASA Astrophysics Data System (ADS)

Menzel, F.; Reinert, T.; Vogt, J.; Butz, T.

2004-06-01

Micronised TiO 2 particles with a diameter of about 15 nm are used in sunscreens as physical UV filter. Due to the small particle size it may be supposed that TiO 2 particles can pass through the uppermost horny skin layer ( stratum corneum) via intercellular channels and penetrate into deeper vital skin layers. Accumulations of TiO 2 particles in the skin can decrease the threshold for allergies of the immune system or cause allergic reactions directly. Spatially resolved ion beam analysis (PIXE, RBS, STIM and secondary electron imaging) was carried out on freeze-dried cross-sections of biopsies of pig skin, on which four different formulations containing TiO 2 particles were applied. The investigations were carried out at the high energy ion nanoprobe LIPSION in Leipzig with a 2.25 MeV proton beam, which was focused to a diameter of 1 μm. The analysis concentrated on the penetration depth and on pathways of the TiO 2 particles into the skin. In these measurements a penetration of TiO 2 particles through the s. corneum into the underlying stratum granulosum via intercellular space was found. Hair follicles do not seem to be important penetration pathways because no TiO 2 was detected inside. The TiO 2 particle concentration in the stratum spinosum was below the minimum detection limit of about 1 particle/μm 2. These findings show the importance of coating the TiO 2 particles in order to prevent damage of RNA and DNA of skin cells by photocatalytic reactions of the penetrated particles caused by absorption of UV light.

Investigating the "g"-Saturation of Various Stratum-Two Factors Using Automatic Item Generation

ERIC Educational Resources Information Center

Arendasy, Martin E.; Hergovich, Andreas; Sommer, Markus

2008-01-01

Even though researchers agree on the hierarchical structure of intelligence there is considerable disagreement on the g-saturation of the lower stratum-two factors. In this article it is argued that the mixed evidence in the research literature can be at least partially attributed to the construct representation of the individual tests used to…

Ambient humidity and the skin: the impact of air humidity in healthy and diseased states.

PubMed

Goad, N; Gawkrodger, D J

2016-08-01

Humidity, along with other climatic factors such as temperature and ultraviolet radiation, can have an important impact on the skin. Limited data suggest that external humidity influences the water content of the stratum corneum. An online literature search was conducted through Pub-Med using combinations of the following keywords: skin, skin disease, humidity, dermatoses, dermatitis, eczema, and mist. Publications included in this review were limited to (i) studies in humans or animals, (ii) publications showing relevance to the field of dermatology, (iii) studies published in English and (iv) publications discussing humidity as an independent influence on skin function. Studies examining environmental factors as composite influences on skin health are only included where the impact of humidity on the skin is also explored in isolation of other environmental factors. A formal systematic review was not feasible for this topic due to the heterogeneity of the available research. Epidemiological studies indicated an increase in eczema with low internal (indoors) humidity and an increase in eczema with external high humidity. Other studies suggest that symptoms of dry skin appear with low humidity internal air-conditioned environments. Murine studies determined that low humidity caused a number of changes in the skin, including the impairment of the desquamation process. Studies in humans demonstrated a reduction in transepidermal water loss (TEWL) (a measure of the integrity of the skin's barrier function) with low humidity, alterations in the water content in the stratum corneum, decreased skin elasticity and increased roughness. Intervention with a humidifying mist increased the water content of the stratum corneum. Conversely, there is some evidence that low humidity conditions can actually improve the barrier function of the skin. Ambient relative humidity has an impact on a range of parameters involved in skin health but the literature is inconclusive. Further

Inhomogeneous Monte Carlo simulations of dermoscopic spectroscopy

NASA Astrophysics Data System (ADS)

Gareau, Daniel S.; Li, Ting; Jacques, Steven; Krueger, James

2012-03-01

Clinical skin-lesion diagnosis uses dermoscopy: 10X epiluminescence microscopy. Skin appearance ranges from black to white with shades of blue, red, gray and orange. Color is an important diagnostic criteria for diseases including melanoma. Melanin and blood content and distribution impact the diffuse spectral remittance (300-1000nm). Skin layers: immersion medium, stratum corneum, spinous epidermis, basal epidermis and dermis as well as laterally asymmetric features (eg. melanocytic invasion) were modeled in an inhomogeneous Monte Carlo model.

Transcutaneous drug delivery by liposomes using fractional laser technology.

PubMed

Fujimoto, Takahiro; Wang, Jian; Baba, Kazuki; Oki, Yuka; Hiruta, Yuki; Ito, Masayuki; Ito, Shinobu; Kanazawa, Hideko

2017-07-01

Transdermal delivery of hydrophilic peptides remains a challenge due to their poor cellular uptake and transdermal penetration. We hypothesize that combination of a CO 2 fractional laser to enhance percutaneous absorption and liposomes as transdermal carriers would improve skin penetration of hydrophilic drugs. NA. Liposomes were prepared using membrane fusion lipid dioleoylphosphatidylethanolamine, and used to deliver 5-carboxyfluorescein (CF) and fluorescein isothiocyanate-conjugated ovalbumin (OVA-FITC) as model hydrophilic peptide drugs. Liposome size was estimated by dynamic light scattering. Liposome uptake into murine macrophage cells and penetration or permeation into Yucatan micropig skin after irradiation by CO 2 fractional laser at varying energy levels (laser power and exposure duration) were investigated using Franz cell and fluorescence microscopy. Oxidative damage to the irradiated mouse skin was assessed by electron spin resonance. Size of CF and OVA-FITC encapsulated liposomes was 324 ± 75 nm. Cellular uptake of OVA-FITC delivered by liposomes was 10-fold higher (1,370 relative fluorescence units, RFU) than delivered in solution form (130 RFU). Fractional laser irradiation increased skin permeation rate of CF liposomes (0-10%) and OVA-FITC liposomes (4-40%) in a dose-dependent manner. Although peeling off the stratum corneum facilitated CF liposome penetration at low energy levels (2.69-3.29 J/cm 2 ; 10-20 W for 500 μs), drug permeation was similar (7-8%) in peeled or untreated skin at higher laser energy levels (6.06 J/cm 2 ; 20 W for 1,500 μs). FITC penetrated deeper in the skin after laser irradiation. However, OH, O2-, and VC reactive oxygen species were generated upon irradiation of the skin with a fractional CO 2 laser. Increasing laser power and irradiation, time increased liposome uptake by cells and penetration of peptide drugs across the skin in a dose-dependent manner. High-energy CO 2 fractional laser overcomes the

Skin penetration behaviour of sesquiterpene lactones from different Arnica preparations using a validated GC-MSD method.

PubMed

Wagner, Steffen; Merfort, Irmgard

2007-01-04

Preparations of Arnica montana L. are widely used for the topical treatment of inflammatory diseases. The anti-inflammatory activity is mainly attributed to their sesquiterpene lactones (SLs) from the helenalin and 11alpha,13-dihydrohelenalin type. To study the penetration kinetics of SLs in Arnica preparations, a stripping method with adhesive tape and pig skin as a model was used. For the determination of SLs in the stripped layers of the stratum corneum (SC), a gas chromatography/mass spectrometry method was developed and validated. Thereby the amount of helenalin derivatives was calculated as helenalin isobutyrate, and 11alpha,13-dihydrohelenalin derivatives as 11alpha,13-dihydrohelenalin methacrylate. This GC-MSD method is suitable also to determine low amounts of SLs in Arnica preparations. The penetration behaviour of one gel preparation and two ointment preparations was investigated. The SLs of all preparations show a comparable penetration in and a permeation through the stratum corneum, the uppermost part of the skin. Interestingly, the gel preparation showed a decrease of the penetration rate over 4h, whereas the penetration rate of ointments kept constant over time. Moreover, we could demonstrate that the totally penetrated amount of SLs only depends on the kind of the formulation and of the SLs-content in the formulation but not on the SLs composition or on the used extraction agent.

Localization of dexamethasone within dendritic core-multishell (CMS) nanoparticles and skin penetration properties studied by multi-frequency electron paramagnetic resonance (EPR) spectroscopy.

PubMed

Saeidpour, S; Lohan, S B; Anske, M; Unbehauen, M; Fleige, E; Haag, R; Meinke, M C; Bittl, R; Teutloff, C

2017-07-01

The skin and especially the stratum corneum (SC) act as a barrier and protect epidermal cells and thus the whole body against xenobiotica of the external environment. Topical skin treatment requires an efficient drug delivery system (DDS). Polymer-based nanocarriers represent novel transport vehicles for dermal application of drugs. In this study dendritic core-multishell (CMS) nanoparticles were investigated as promising candidates. CMS nanoparticles were loaded with a drug (analogue) and were applied to penetration studies of skin. We determined by dual-frequency electron paramagnetic resonance (EPR) how dexamethasone (Dx) labelled with 3-carboxy-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (PCA) is associated with the CMS. The micro-environment of the drug loaded to CMS nanoparticles was investigated by pulsed high-field EPR at cryogenic temperature, making use of the fact that magnetic parameters (g-, A-matrices, and spin-lattice relaxation time) represent specific probes for the micro-environment. Additionally, the rotational correlation time of spin-labelled Dx was probed by continuous wave EPR at ambient temperature, which provides independent information on the drug environment. Furthermore, the penetration depth of Dx into the stratum corneum of porcine skin after different topical applications was investigated. The location of Dx in the CMS nanoparticles is revealed and the function of CMS as penetration enhancers for topical application is shown. Copyright © 2016 Elsevier B.V. All rights reserved.

A thermal microjet system with tapered micronozzles fabricated by inclined UV lithography for transdermal drug delivery

NASA Astrophysics Data System (ADS)

Yoon, Yong-Kyu; Park, Jung-Hwan; Lee, Jeong-Woo; Prausnitz, Mark R.; Allen, Mark G.

2011-02-01

Transdermal drug delivery can be enabled by various methods that increase the permeability of the skin's outer barrier of stratum corneum, including skin exposure to heat and chemical enhancers, such as ethanol. Combining these approaches for the first time, in this study we designed a microdevice consisting of an array of microchambers filled with ethanol that is vaporized using an integrated microheater and ejected through a micronozzle contacting the skin surface. In this way, we hypothesize that the hot ethanol vapor can increase skin permeability upon contacting the skin surface. The tapered micronozzle and the microchamber designed for this application were realized using proximity-mode inclined rotational ultraviolet lithography, which facilitates easy fabrication of complex three-dimensional structures, convenient integration with other functional layers, low fabrication cost, and mass production. The resulting device had a micronozzle with an orifice inner and outer diameter of 220 and 320 µm, respectively, and an extruded height of 250 µm. When the microchamber was filled with an ethanol gel and activated, the resulting ethanol vapor jet increased the permeability of human cadaver epidermis to a model compound, calcein, by approximately 17 times, which is attributed to thermal and chemical disruption of stratum corneum structure. This thermal microjet system can serve as a tool not only for transdermal drug delivery, but also for a variety of biomedical applications.

Microemulsion and Microemulsion-Based Gels for Topical Antifungal Therapy with Phytochemicals.

PubMed

Boonme, Prapaporn; Kaewbanjong, Jarika; Amnuaikit, Thanaporn; Andreani, Tatiana; Silva, Amélia M; Souto, Eliana B

2016-01-01

Skin fungal infections are regular injuries suffered by people living in tropical areas. Most common pathogens are Trichophyton, Microsporum and Epidermophyton which can cause skin lesions in many parts of body. Topical antifungal phytochemicals are commonly used to avoid systemic adverse events and are more convenient for patient application than those administered by other routes. However, the effectiveness of topical treatments in eradicating fungal infection is more limited since the stratum corneum acts as the skin barrier, resulting in long treatment duration and low patient's compliance. The goal of this work is to identify optimized drug delivery systems to improve topic clinical efficacy. Microemulsions i.e. liquid dispersions of oil and water stabilized with an interfacial film of surfactant are well known drug delivery systems. A thickening agent may be included to form microemulsion-based gels to increase skin adhesion. Microemulsions and microemulsion-based gels can be loaded with several hydrophilic and lipophilic drugs because they are composed of both water and oil phases. Microemulsions and microemulsion-based gels can also be used for the delivery of many drugs including antifungal drugs through stratum corneum due to their capacity to act as skin penetration enhancement. In addition to a comprehensive review of microemulsion and microemulsion-based gels as suitable carriers for skin delivery of various antifungal drugs, this review also aims to discuss the delivery of antifungal phytochemicals.

Moisturizing and Antiinflammatory Properties of Cosmetic Formulations Containing Centella asiatica Extract

PubMed Central

Ratz-Łyko, A.; Arct, J.; Pytkowska, K.

2016-01-01

Centella asiatica extract is a rich source of natural bioactive substances, triterpenoid saponins, flavonoids, phenolic acids, triterpenic steroids, amino acids and sugars. Thus, many scavenging free radicals, exhibit antiinflammatory activity and affect on the stratum corneum hydration and epidermal barrier function. The aim of the present study was to evaluate the in vivo moisturizing and antiinflammatory properties of cosmetic formulations (oil-in-water emulsion cream and hydrogel) containing different concentrations of Centella asiatica extract. The study was conducted over four weeks on a group of 25 volunteers after twice a day application of cosmetic formulations with Centella asiatica extract (2.5 and 5%, w/w) on their forearms. The measurement of basic skin parameters (stratum corneum hydration and epidermal barrier function) was performed once a week. The in vivo antiinflammatory activity based on the methyl nicotinate model of microinflammation in human skin was evaluated after four weeks application of tested formulations. In vivo tests formulations containing 5% of Centella asiatica extract showed the best efficacy in improving skin moisture by increase of skin surface hydration state and decrease in transepidermal water loss as well as exhibited antiinflammatory properties based on the methyl nicotinate model of microinflammation in human skin. Comparative tests conducted by corneometer, tewameter and chromameter showed that cosmetic formulations containing Centella asiatica extract have the moisturizing and antiinflammatory properties. PMID:27168678

In vitro percutaneous absorption studies and in vivo evaluation of anti-inflammatory activity of essential fatty acids (EFA) from fish oil extracts.

PubMed

Puglia, Carmelo; Tropea, Salvatore; Rizza, Luisa; Santagati, Natale Alfredo; Bonina, Francesco

2005-08-11

The aim of the present study was to evaluate the in vitro percutaneous absorption and the in vivo anti-inflammatory activity of EPA and DHA fatty acids from three oily extracts, obtained by acetonic extractions from the entrails of different varieties of Mediterranean fishes such as mackerel (Scomber scombrus), sardine (Sardina pilchardus) and horse mackerel (Trachurus mediterraneus). In the first part of our research, we focused our attention on the characterization of the oily extracts to determine their omega-3 polyunsaturated fatty acid content, then, we evaluated the in vitro percutaneous absorption through excised human skin (stratum corneum/epidermis membranes; SCE) of EPA and DHA contained in the extracts. In the second part, the fish oil which guaranteed the best in vitro permeation profile of these omega-3 fatty acids was studied in order to evaluate its inhibiting ability towards the in vivo UVB-induced skin erythema. From the results obtained, all the fish oils tested in this study presented significant amounts of omega-3 fatty acids EPA and DHA, and particularly sardine oil extract showed higher concentrations of these substances compared to the other two fish oils. The in vitro experiments revealed interesting fluxes of these compounds from sardine extract through the stratum corneum/epidermis membranes and an appreciable anti-inflammatory activity against UVB-induced erythema in human volunteers was also observed.

Effect of forage inclusion and particle size in diets of neonatal lambs on performance and rumen development.

PubMed

Norouzian, M A; Valizadeh, R

2014-12-01

A slaughter experiment was conducted to determine the effects of alfalfa particle size on rumen morphology and performance of lambs. Twenty-four Balouchi lambs aged 21 days (9.1 ± 1.1 kg) were randomly fed control (diet without alfalfa hay; CON) and mixed rations containing 15% finely ground (FINE; 2 mm) and 15% coarsely chopped alfalfa hay (LONG; 3 to 4 cm). After a 63 days feeding period, nine animals (three per treatment) were slaughtered to obtain ruminal tissue samples for morphological analyses. Alfalfa particle size did not affect (p > 0.05) papillae density, height, width, epithelium depth and surface area. Coarse alfalfa decreased the stratum corneum and increased (p < 0.05) muscle depth compared with fine and control diets. Neither DNA content and nor RNA concentration of rumen tissue was affected by feeding different diets. Forage particle size did not affect the blood concentration of glucose, urea nitrogen (BUN), beta-hydroxybutyric acid (BHBA) and non-esterified fatty acids (NEFA). Dry matter intake and feed conversion ratio were higher for control diet; however, there were no significant differences between treatments for average daily gain. These data suggest that coarse alfalfa significantly reduces the stratum corneum and increases muscularity of rumen wall and tended to better feed conversion ratio. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

Enhanced topical delivery of finasteride using glyceryl monooleate-based liquid crystalline nanoparticles stabilized by cremophor surfactants.

PubMed

Madheswaran, Thiagarajan; Baskaran, Rengarajan; Yong, Chul Soon; Yoo, Bong Kyu

2014-02-01

The aim of this study was to investigate the capability of two surfactants, Cremophor RH 40 (RH) and Cremophor EL (EL), to prepare liquid crystalline nanoparticles (LCN) and to study its influence on the topical delivery of finasteride (FNS). FNS-loaded LCN was formulated with the two surfactants and characterized for size distribution, morphology, entrapment efficiency, in vitro drug release, and skin permeation/retention. Influence of FNS-loaded LCN on the conformational changes on porcine skin was also studied using attenuated total reflectance Fourier-transform infrared spectroscopy. Transmission electron microscopical image confirmed the formation of LCN. The average particle size of formulations was in the range of 165.1-208.6 and 153.7-243.0 nm, respectively. The formulations prepared with higher surfactant concentrations showed faster release and significantly increased skin permeation. Specifically, LCN prepared with RH 2.5% presented higher permeation flux (0.100 ± 0.005 μgcm(-2)h(-1)) compared with lower concentration (0.029 ± 0.007 μgcm(-2)h(-1)). Typical spectral bands of lipid matrix of porcine skin were shifted to higher wavenumber, indicating increased degree of disorder of the lipid acyl chains which might cause fluidity increase of stratum corneum. Taken together, Cremophor surfactants exhibited a promising potential to stabilize the LCN and significantly augmented the skin permeation of FNS.

Acral peeling skin syndrome: a case of two brothers.

PubMed

Wakade, Oojwala; Adams, Beth; Shwayder, Tor

2009-01-01

We report two brothers of Middle Eastern descent with consanguineous parents who present with numerous fragile, flaccid blisters on the hands and feet. In addition to spontaneous peeling, they can manually peel skin from acral areas without pain. The symptoms worsen with warm temperatures, excessive water exposure, and perspiration. Two biopsies from flaccid blisters on the feet were taken from the older brother, which revealed cleavage at the level of the stratum corneum. A diagnosis of acral peeling skin syndrome was made.

Clinical experience with Leptospermum honey use for treatment of hard to heal neonatal wounds: case series.

PubMed

Boyar, V; Handa, D; Clemens, K; Shimborske, D

2014-02-01

Preterm, critically ill neonates represent a challenge in wound healing. Many factors predispose infants to skin injuries, including decreased epidermal-dermal cohesion, deficient stratum corneum, relatively alkaline pH of skin surface, impaired nutrition and presence of multiple devices on the skin. We present a case series describing the use of medical-grade honey-Leptospermum honey (Medihoney), for successful treatment of slowly healing neonatal wounds, specifically stage 3 pressure ulcer, dehiscent and infected sternal wound, and full-thickness wound from an extravasation injury.

Intravital multiphoton tomography as an appropriate tool for non-invasive in vivo analysis of human skin affected with atopic dermatitis

NASA Astrophysics Data System (ADS)

Huck, Volker; Gorzelanny, Christian; Thomas, Kai; Mess, Christian; Dimitrova, Valentina; Schwarz, Martin; Riemann, Iris; Niemeyer, Verena; Luger, Thomas A.; König, Karsten; Schneider, Stefan W.

2011-03-01

Increasing incidence of inflammatory skin diseases such as Atopic Dermatitis (AD) has been noted in the past years. According to recent estimations around 15% of newborn subjects are affected with a disease severity that requires medical treatment. Although its pathogenesis is multifactorial, recent reports indicate that an impaired physical skin barrier predispose for the development of AD. The major part of this barrier is formed by the stratum corneum (SC) wherein corneocytes are embedded in a complex matrix of proteins and lipids. Its components were synthesized in the stratum granulosum (SG) and secreted via lamellar bodies at the SC/SG interface. Within a clinical in vivo study we focused on the skin metabolism at the SC/SG interface in AD affected patients in comparison to healthy subjects. Measurement of fluorescence life-time of NADH provides access to the metabolic state of skin. Due to the application of a 5D intravital tomographic skin analysis we facilitate the non-invasive investigation of human epidermis in the longitudinal course of AD therapy. We could ascertain by blinded analysis of 40 skin areas of 20 patients in a three month follow-up that the metabolic status at the SC/SG interface was altered in AD compromised skin even in non-lesional, apparent healthy skin regions. This illustrates an impaired skin barrier formation even at non-affected skin of AD subjects appearing promotive for the development of acute skin inflammation. Therefore, our findings allow a deeper understanding of the individual disease development and the improved management of the therapeutic intervention in clinical application.

Skin Membrane Electrical Impedance Properties under the Influence of a Varying Water Gradient

PubMed Central

Björklund, Sebastian; Ruzgas, Tautgirdas; Nowacka, Agnieszka; Dahi, Ihab; Topgaard, Daniel; Sparr, Emma; Engblom, Johan

2013-01-01

The stratum corneum (SC) is an effective permeability barrier. One strategy to increase drug delivery across skin is to increase the hydration. A detailed description of how hydration affects skin permeability requires characterization of both macroscopic and molecular properties and how they respond to hydration. We explore this issue by performing impedance experiments on excised skin membranes in the frequency range 1 Hz to 0.2 MHz under the influence of a varying gradient in water activity (aw). Hydration/dehydration induces reversible changes of membrane resistance and effective capacitance. On average, the membrane resistance is 14 times lower and the effective capacitance is 1.5 times higher when the outermost SC membrane is exposed to hydrating conditions (aw = 0.992), as compared to the case of more dehydrating conditions (aw = 0.826). Molecular insight into the hydration effects on the SC components is provided by natural-abundance 13C polarization transfer solid-state NMR and x-ray diffraction under similar hydration conditions. Hydration has a significant effect on the dynamics of the keratin filament terminals and increases the interchain spacing of the filaments. The SC lipids are organized into lamellar structures with ∼ 12.6 nm spacing and hexagonal hydrocarbon chain packing with mainly all-trans configuration of the acyl chains, irrespective of hydration state. Subtle changes in the dynamics of the lipids due to mobilization and incorporation of cholesterol and long-chain lipid species into the fluid lipid fraction is suggested to occur upon hydration, which can explain the changes of the impedance response. The results presented here provide information that is useful in explaining the effect of hydration on skin permeability. PMID:23790372

Functional analyses of the skin surface of the areola mammae: comparison between healthy adult male and female subjects and between healthy individuals and patients with atopic dermatitis.

PubMed

Kikuchi, K; Tagami, H; Akaraphanth, R; Aiba, S

2011-01-01

Although the nipple and areola of the breast constitute a unique and prominent area on the chest, so far no study has been done on the functional properties of their skin surfaces. To study the stratum corneum (SC) covering the areola using noninvasive methods. Eighteen adult healthy subjects comprising nine men and nine women and 18 age- and sex-matched patients with atopic dermatitis (AD), none of whom had visible skin lesions, participated in the study. Transepidermal water loss (TEWL), skin surface hydration and skin surface lipid levels were measured on the areola and adjacent breast skin. The size of the skin surface corneocytes of these skin regions was assessed. All the healthy subjects showed significantly higher TEWL accompanied by smaller sized corneocytes on the areola than on the adjacent breast skin. Only female subjects revealed a significantly higher skin surface hydration state together with significantly increased skin surface lipid levels on the areola than on the adjacent breast skin. These sex differences were observed even in patients with AD. Comparison between healthy individuals and the patients with AD demonstrated higher TEWL, decreased skin surface hydration state and lower skin surface lipid levels associated with smaller sized corneocytes in the areola in the patients with AD, especially in male patients. In adults, the SC barrier function and SC water-binding capacity of the areola were functionally poorer than in the adjacent skin, being covered by smaller sized corneocytes and lower amounts of skin surface lipids, especially in men and in patients with AD. © 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.

Impact of the gap between socioeconomic stratum and subjective social class on depressive symptoms: unique insights from a longitudinal analysis.

PubMed

Kim, Jae-Hyun; Lee, Sang Gyu; Shin, Jaeyong; Park, Eun-Cheol

2014-11-01

Our objective was to investigate whether gaps between socioeconomic stratum and subjective social class affect the prevalence of depressive symptoms. We collected data from the Korean Health Panel Survey, years 2009 and 2011, and performed a longitudinal analysis of 12,357 individuals at baseline (2009), estimating the prevalence of depressive symptoms among individuals with disparate socioeconomic stratum (High, Middle, or Low household income and education level, respectively) and subjective social class (High, Middle, or Low). The odds ratio for depressive symptoms among individuals with High household income and High social class, or Low household income and Low social class, was 0.537 and 1.877, respectively (p<0.0001), and that among individuals with High education level and High social class, or Low education and Low social class, was 0.700 and 1.597, respectively (p: 0.001, p<0.0001, respectively). The likelihood of having depressive symptoms increased within each level of income and education, as the subjective social class decreased from High to Low. The adjusted effect of the gap between socioeconomic stratum and subjective social class on depressive symptoms deteriorated, as a whole, across the socioeconomic spectrum. The gap between socioeconomic stratum and perceived position in the social hierarchy explains a substantial part of inequalities in the prevalence of depressive symptoms. It is important to consider the impact of discrepancies between different measures of socioeconomic well-being on depressive symptoms rather than looking at the subjective social class alone. Copyright © 2014 The Authors. Published by Elsevier Ltd. All rights reserved.

Skin permeation mechanism and bioavailability enhancement of celecoxib from transdermally applied nanoemulsion

PubMed Central

Shakeel, Faiyaz; Baboota, Sanjula; Ahuja, Alka; Ali, Javed; Shafiq, Sheikh

2008-01-01

Background Celecoxib, a selective cyclo-oxygenase-2 inhibitor has been recommended orally for the treatment of arthritis and osteoarthritis. Long term oral administration of celecoxib produces serious gastrointestinal side effects. It is a highly lipophilic, poorly soluble drug with oral bioavailability of around 40% (Capsule). Therefore the aim of the present investigation was to assess the skin permeation mechanism and bioavailability of celecoxib by transdermally applied nanoemulsion formulation. Optimized oil-in-water nanoemulsion of celecoxib was prepared by the aqueous phase titration method. Skin permeation mechanism of celecoxib from nanoemulsion was evaluated by FTIR spectral analysis, DSC thermogram, activation energy measurement and histopathological examination. The optimized nanoemulsion was subjected to pharmacokinetic (bioavailability) studies on Wistar male rats. Results FTIR spectra and DSC thermogram of skin treated with nanoemulsion indicated that permeation occurred due to the disruption of lipid bilayers by nanoemulsion. The significant decrease in activation energy (2.373 kcal/mol) for celecoxib permeation across rat skin indicated that the stratum corneum lipid bilayers were significantly disrupted (p < 0.05). Photomicrograph of skin sample showed the disruption of lipid bilayers as distinct voids and empty spaces were visible in the epidermal region. The absorption of celecoxib through transdermally applied nanoemulsion and nanoemulsion gel resulted in 3.30 and 2.97 fold increase in bioavailability as compared to oral capsule formulation. Conclusion Results of skin permeation mechanism and pharmacokinetic studies indicated that the nanoemulsions can be successfully used as potential vehicles for enhancement of skin permeation and bioavailability of poorly soluble drugs. PMID:18613981

Measurement of the Biomechanical Function and Structure of Ex Vivo Drying Skin Using Raman Spectral Analysis and its Modulation with Emollient Mixtures.

PubMed

Biniek, Krysta; Tfayli, Ali; Vyumvuhore, Raoul; Quatela, Alessia; Galliano, Marie-Florence; Delalleau, Alexandre; Baillet-Guffroy, Arlette; Dauskardt, Reinhold H; Duplan, Helene

2018-06-22

An important aspect of the biomechanical behavior of the stratum corneum (SC) is the drying stresses that develop with water loss. These stresses act as a driving force for damage in the form of chapping and cracking. Betasitosterol is a plant sterol with a structure similar to cholesterol, a key component in the intercellular lipids of the outermost layer of human skin, the SC. Cholesterol plays an important role in stabilizing the SC lipid structure, and altered levels of cholesterol have been linked with SC barrier abnormalities. Betasitosterol is currently applied topically to skin for treatment of wounds and burns. However, it is unknown what effect betasitosterol has on the biomechanical barrier function of skin. Here, by analyzing the drying stress profile of SC generated during a kinetics of dehydration, we show that betasitosterol, in combination with two emollient molecules, isocetyl stearoyl stearate (ISS) and glyceryl tri-2-ethylhexanoate (GTEH), causes a significant modulation of the drying stress behavior of the SC by reducing both the maximal peak stress height and average plateau of the drying stress profile. Raman spectra analyses demonstrate that the combination of betasitosterol with the two emollients, ISS and GTEH, allows a high water retention capacity within the SC, while the lipid conformational order by increasing the amount of trans conformers. Our study highlights the advantage of combining a biomechanical approach together with Raman spectroscopy in engineering a suitable combination of molecules for alleviating dryness and dry skin damage. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Acral peeling skin syndrome resembling epidermolysis bullosa simplex in a 10-month-old boy.

PubMed

Kavaklieva, S; Yordanova, I; Bruckner-Tuderman, L; Has, C

2013-01-01

The acral peeling skin syndrome (APSS) is a rare autosomal recessive disorder clinically characterized by asymptomatic desquamation of the skin limited to the hands and feet and histologically by cleavage at the stratum granulosum and stratum corneum level [Kiritsi et al.: J Invest Dermatol 2010;130:1741-1746]. We report on a 10-month-old boy with a history of skin peeling limited to the hands and feet since 2 months of age. Clinical examination revealed erythematous erosions with peripheral desquamation and flaccid blisters. DNA mutation analysis detected two heterozygous TGM5 mutations: c.2T>C, p.M1T in exon 1 and c.337G>T, p.G113C in exon 3 in keeping with the diagnosis of APSS. The clinical presentation of APSS alone might be confusing and strongly resemble epidermolysis bullosa simplex making the differential diagnosis difficult.

Biokinetics and Biodynamics of Nanomaterial Interactions

DTIC Science & Technology

2009-09-30

HEK viability. The medium from each treatment set of the dosed cells was removed, pooled into a microfuge tube , and quickly frozen to -80ºC until...Trump’s fixative at 4ºC. The cells were rinsed in 0.1M phosphate buffer (pH 7.2), pelleted in a microfuge tube , resuspended, and quickly pelleted in 3...formulation on in vitro human skin localized NP in the upper stratum corneum with minimal penetration (Cross et al., 2007) and microfine zinc oxide with a

Performance evaluation of multi-stratum resources optimization with network functions virtualization for cloud-based radio over optical fiber networks.

PubMed

Yang, Hui; He, Yongqi; Zhang, Jie; Ji, Yuefeng; Bai, Wei; Lee, Young

2016-04-18

Cloud radio access network (C-RAN) has become a promising scenario to accommodate high-performance services with ubiquitous user coverage and real-time cloud computing using cloud BBUs. In our previous work, we implemented cross stratum optimization of optical network and application stratums resources that allows to accommodate the services in optical networks. In view of this, this study extends to consider the multiple dimensional resources optimization of radio, optical and BBU processing in 5G age. We propose a novel multi-stratum resources optimization (MSRO) architecture with network functions virtualization for cloud-based radio over optical fiber networks (C-RoFN) using software defined control. A global evaluation scheme (GES) for MSRO in C-RoFN is introduced based on the proposed architecture. The MSRO can enhance the responsiveness to dynamic end-to-end user demands and globally optimize radio frequency, optical and BBU resources effectively to maximize radio coverage. The efficiency and feasibility of the proposed architecture are experimentally demonstrated on OpenFlow-based enhanced SDN testbed. The performance of GES under heavy traffic load scenario is also quantitatively evaluated based on MSRO architecture in terms of resource occupation rate and path provisioning latency, compared with other provisioning scheme.

Soybean-fragmented proteoglycans against skin aging.

PubMed

Barba, Clara; Alonso, Cristina; Sánchez, Isabel; Suñer, Elisa; Sáez-Martín, L C; Coderch, Luisa

2017-08-01

The majority of age-dependent skin changes happen in the dermis layer inducing changes in skin collagen and in the proteoglycans. The main aim of this work is to study the efficacy of a Proteum serum, containing soybean-fragmented proteoglycans, against skin aging. In vitro tests were performed to evaluate the Proteum serum ability on activating the production of collagen and proteoglycans. An in vivo long-term study was performed to determine the efficacy of the Proteum serum when applied on skin. Protection of healthy skin against detergent-induced dermatitis and the antioxidant properties of the applied Proteum serum were also studied. The in vitro tests demonstrated that the Proteum serum was able to elevate the production of molecules which are essential for supporting the dermal extracellular matrix organization. These results were correlated by the in vivo measurements where a clear trend on improving the measured skin parameters due to the Proteum serum application was found. A beneficial effect of the Proteum serum was demonstrated with an improvement in the skin roughness and a reinforcement of the skin barrier function. Moreover, a significant protector effect on human stratum corneum against lipids peroxides (LPO) was demonstrated.

Confocal spectroscopic imaging measurements of depth dependent hydration dynamics in human skin in-vivo

NASA Astrophysics Data System (ADS)

Behm, P.; Hashemi, M.; Hoppe, S.; Wessel, S.; Hagens, R.; Jaspers, S.; Wenck, H.; Rübhausen, M.

2017-11-01

We present confocal spectroscopic imaging measurements applied to in-vivo studies to determine the depth dependent hydration profiles of human skin. The observed spectroscopic signal covers the spectral range from 810 nm to 2100 nm allowing to probe relevant absorption signals that can be associated with e.g. lipid and water-absorption bands. We employ a spectrally sensitive autofocus mechanism that allows an ultrafast focusing of the measurement spot on the skin and subsequently probes the evolution of the absorption bands as a function of depth. We determine the change of the water concentration in m%. The water concentration follows a sigmoidal behavior with an increase of the water content of about 70% within 5 μm in a depth of about 14 μm. We have applied our technique to study the hydration dynamics of skin before and after treatment with different concentrations of glycerol indicating that an increase of the glycerol concentration leads to an enhanced water concentration in the stratum corneum. Moreover, in contrast to traditional corneometry we have found that the application of Aluminium Chlorohydrate has no impact to the hydration of skin.

In Silico Modelling of Transdermal and Systemic Kinetics of Topically Applied Solutes: Model Development and Initial Validation for Transdermal Nicotine.

PubMed

Chen, Tao; Lian, Guoping; Kattou, Panayiotis

2016-07-01

The purpose was to develop a mechanistic mathematical model for predicting the pharmacokinetics of topically applied solutes penetrating through the skin and into the blood circulation. The model could be used to support the design of transdermal drug delivery systems and skin care products, and risk assessment of occupational or consumer exposure. A recently reported skin penetration model [Pharm Res 32 (2015) 1779] was integrated with the kinetic equations for dermis-to-capillary transport and systemic circulation. All model parameters were determined separately from the molecular, microscopic and physiological bases, without fitting to the in vivo data to be predicted. Published clinical studies of nicotine were used for model demonstration. The predicted plasma kinetics is in good agreement with observed clinical data. The simulated two-dimensional concentration profile in the stratum corneum vividly illustrates the local sub-cellular disposition kinetics, including tortuous lipid pathway for diffusion and the "reservoir" effect of the corneocytes. A mechanistic model for predicting transdermal and systemic kinetics was developed and demonstrated with published clinical data. The integrated mechanistic approach has significantly extended the applicability of a recently reported microscopic skin penetration model by providing prediction of solute concentration in the blood.

Evaluation of the effect of hydroxypropyl-β-cyclodextrin on topical administration of milk thistle extract.

PubMed

Spada, Gianpiera; Gavini, Elisabetta; Cossu, Massimo; Rassu, Giovanna; Carta, Antonio; Giunchedi, Paolo

2013-01-30

Two water in oil emulsions composed by eudermic ingredients as glycerin, cocoa butter, almond oil and a variety of lipids, were enriched respectively with milk thistle dry extract (MT) or with a binary complex composed by MT and hydroxypropyl-β-cyclodextrin (HP) (1:4 w/w) correspondent to 1% (w/w) in sylimarine in order to obtain two different emulsions designed for the skin delivery and determine influence of hydroxypropyl-β-cyclodextrin on the extract delivery and permeation. Uv-vis spectrophotometric analyses demonstrated that phytocomplex formation influences the finding of MT after the complexation process and the in vitro antioxidant activity. Further in vitro and ex vivo experiments demonstrated that the penetration capability of MT from formulations is strictly influenced by the phytocomplex able to control MT permeation; moreover phytocomplex increases flavonoids stability during the in vitro tests. Additionally, in vivo studies showed that the penetration into the stratum corneum of the active ingredients is effectively achieved by the phytocomplex formation, in fact about 80% of MT is absorbed by the skin along 1h despite the 30% of MT not complexed absorbed during the same period. Copyright © 2012 Elsevier Ltd. All rights reserved.

Comparative behavior between sunscreens based on free or encapsulated UV filters in term of skin penetration, retention and photo-stability.

PubMed

Cozzi, Arianna C; Perugini, Paola; Gourion-Arsiquaud, Samuel

2018-06-03

The growing incidence of photodamaging effects caused by UV radiation (e.g. sunburn, skin cancer) has increased the attention from health authorities which recommend the topical application of sunscreens to prevent these skin damages. The economic stakes for those companies involved in this international market are to develop new UV filters and innovative technologies to provide the most efficient, flexible and robust sunscreen products. Today the development of innovative and competitive sunscreen products is a complex formulation challenge. Indeed, the current sunscreens must protect against skin damages, while also being safe for the skin and being sensory and visually pleasant for the customers when applied on the skin. Organic UV filters, while proposing great advantages, also present the risk to penetrate the stratum corneum and diffuse into underlying structures with unknown consequences; moreover, their photo-stability are noted thorny outcomes in sunscreen development and subsequent performance. In recent years, the evaluation of the interaction between skin and sunscreen in terms of penetration after topical application has been considered from European authority but still its testing as their photo-stability assessment are not mandatory in most countries. This study, based on in-vitro approaches, was performed to evaluate and compare the retention and the penetration of organic UV filters in free or encapsulated form inside the skin as well as their respective photo-stability. Sunscreen formulation with a combination of Avobenzone and Octocrylene in "free form" and a formulation using the same UV filters but encapsulated in a sol-gel silica capsule, were analyzed and compared by FTIR Imaging Spectroscopy. Tape stripping method was used to investigate the penetration of these UV filters inside the stratum corneum. Their photo-stabilities were evaluated by spectroscopic measurements (FTIR, UV/Vis) and standard measurements were calculated: AUC (Area Under

OCT analysis of microneedle and Er:YAG surface ablation for enhanced transdermal delivery of hyperosmotic agents for optical skin clearing

NASA Astrophysics Data System (ADS)

Stumpp, Oliver F.; Welch, A. J.; Gill, Harvinder S.; Prausnitz, Mark R.

2004-07-01

The purpose of this study is to investigate the feasibility of using microneedles in comparison to Er:YAG skin surface laser ablation as a means to modify the epidermis of in-vitro hamster skin to facilitate delivery of topically applied hyper-osmotics such as glycerol into the skin to achieve optical skin clearing. This allows to temporarily reduce scattering of light in otherwise turbid tissues with potential applications pertaining to non-invasive optical imaging techniques such as optical coherence tomography (OCT) or therapeutic applications like laser blood vessel coagulation to treat port wine stains in skin. A portable, battery powered Er:YAG laser (Lasette) manufactured by Cell Robotics Inc. was used to produce holes in the stratum corneum and epidermis using individual 400 μs pulses causing localized ablation. Following each laser pulse the tissue was mechanically translated by 1 mm before another pulse was delivered. As an alternative method to the use of an expensive laser source requiring some kind of light scanning mechanism to treat larger skin areas efficiently, microneedles were investigated. They do not require an energy supply, are also pain-free and can be manufactured into arrays allowing treatment of larger skin areas. A single application forms micron scale holes in the stratum corneum through which topically applied skin clearing agents such as glycerol can penetrate into the tissue. In this feasibility study individual microneedles were used to manually induce holes in the skin each spaced approximately 1 mm apart from the other. Upon such epidermal modification by either technique, glycerol was then applied to the tissue surface and amplitude OCT measurements monitored changes of the optical properties of the tissue over time. Due to the geometry of the microneedle used in this study the cross sectional area of each hole in the epidermis was about 68% smaller than the comparable ablation site caused by an individual laser pulse. Results

Effect of skin barrier disruption on immune responses to topically applied cross-reacting material, CRM(197), of diphtheria toxin.

PubMed

Godefroy, S; Peyre, M; Garcia, N; Muller, S; Sesardic, D; Partidos, C D

2005-08-01

The high accessibility of the skin and the presence of immunocompetent cells in the epidermis makes this surface an attractive route for needle-free administration of vaccines. However, the lining of the skin by the stratum corneum is a major obstacle to vaccine delivery. In this study we examined the effect of skin barrier disruption on the immune responses to the cross-reacting material CRM(197), a nontoxic mutant of diphtheria toxin (DTx) that is considered as a vaccine candidate. Application of CRM(197), together with cholera toxin (CT), onto the tape-stripped skin of mice elicited antibody responses that had anti-DTx neutralizing activity. Vaccine delivery onto mildly ablated skin or intact skin did not elicit any detectable anti-CRM(197) antibodies. Mice immunized with CRM(197) alone onto the tape-stripped skin mounted a vigorous antigen-specific proliferative response. In contrast, the induction of cellular immunity after CRM(197) deposition onto mildly ablated or intact skin was adjuvant dependent. Furthermore, epidermal cells were activated and underwent apoptosis that was more pronounced when the stratum corneum was removed by tape stripping. Overall, these findings highlight the potential for transcutaneous delivery of CRM(197) and establish a correlation between the degree of barrier disruption and levels of antigen-specific immune responses. Moreover, these results provide the first evidence that the development of a transcutaneous immunization strategy for diphtheria, based on simple and practical methods to disrupt the skin barrier, is feasible.

Usefulness and pharmacokinetic study of oral terbinafine for hyperkeratotic-type tinea pedis.

PubMed

Kikuchi, Izumi; Tanuma, Hiroyuki; Morimoto, Kensuke; Kawana, Seiji

2008-11-01

To study and establish an optimal administration method of oral antifungal, terbinafine (TBF), for hyperkeratotic-type tinea pedis from the pharmacokinetic point of view, 20 patients with hyperkeratotic-type tinea pedis were given TBF 125 mg once daily for 4 weeks and observed over time for improvement of dermatological symptoms and mycological efficacy. Targeting five of the patients, TBF concentration in the stratum corneum was measured using the LC-MS/MS method. TBF was detected in the stratum corneum of the sole 1 week after beginning the treatment in some cases and reached its peak 1 week after the completion of the treatment with a concentration of 247.8 ng g(-1), which was approximately more than 50 times higher than its minimal inhibitory concentration against dermatophytes. TBF was not detected at 8 weeks post-treatment, although its concentration was 50.73 ng g(-1) at 6 weeks post-treatment. All cases were subjected to analysis for final total efficacy, general safety and usefulness. Its effectiveness rate (effective + markedly effective) was 95% (19/20) with no adverse reactions, including abnormal changes in the laboratory test values, in any patients. From the above, it is noted that TBF showed excellent efficacy and safety for refractory hyperkeratotic-type tinea pedis, and also it was considered as a useful drug to treat cutaneous mycosis, including hyperkeratotic-type tinea pedis, from the pharmacokinetic point of view.

Morphological study of human sweat ducts for the investigation of THz-wave interaction (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kawase, Kodo; Tripathi, Saroj R.

2016-03-01

Recently, some studies reported that the sweat ducts act as a low-Q-factor helical antenna due to their helical structure, and resonate in the terahertz frequency range according to their structural parameters. According to the antenna theory, when the duct works as a helical antenna, the dimension of the helix plays a key role to determine the frequency of resonance. Therefore, the accurate determination of structural parameters of sweat duct is crucially important to obtain the reliable frequency of resonance and modes of operations. Therefore, here we performed the optical coherence tomography (OCT) of human subjects on their palm and foot to investigate the density, distribution and morphological features of sweat ducts. Moreover, we measured the dielectric properties of stratum corneum using terahertz time domain spectroscopy and based upon this information, we determined the frequency of resonance. We recruited 32 subjects for the measurement and the average duct diameter was 95±11μm. Based upon this information on diameter of duct and THz dielectric properties of stratum corneum (ɛ=5.1±1.3), we have calculated the frequency of resonance of sweat duct. Finally, we determined that the center frequency of resonance was 442±76 GHz. We believe that these findings will facilitate further investigation of the THz-skin interaction and provide guidelines for safety levels with respect to human exposure. We will also report on the EEG measurement while being shined by micro watt order THz waves.

Determination of the effect of lipophilicity on the in vitro permeability and tissue reservoir characteristics of topically applied solutes in human skin layers.

PubMed

Cross, Sheree E; Magnusson, Beatrice M; Winckle, Gareth; Anissimov, Yuri; Roberts, Michael S

2003-05-01

In order to establish the relationship between solute lipophilicity and skin penetration (including flux and concentration behavior), we examined the in vitro penetration and membrane concentration of a series of homologous alcohols (C2-C10) applied topically in aqueous solutions to human epidermal, full-thickness, and dermal membranes. The partitioning/distribution of each alcohol between the donor solution, stratum corneum, viable epidermis, dermis, and receptor phase compartments was determined during the penetration process and separately to isolated samples of each tissue type. Maximum flux and permeability coefficients are compared for each membrane and estimates of alcohol diffusivity are made based on flux/concentration data and also the related tissue resistance (the reciprocal of permeability coefficient) for each membrane type. The permeability coefficient increased with increasing lipophilicity to alcohol C8 (octanol) with no further increase for C10 (decanol). Log vehicle:stratum corneum partition coefficients were related to logP, and the concentration of alcohols in each of the tissue layers appeared to increase with lipophilicity. No difference was measured in the diffusivity of smaller more polar alcohols in the three membranes; however, the larger more lipophilic solutes showed slower diffusivity values. The study showed that the dermis may be a much more lipophilic environment than originally believed and that distribution of smaller nonionized solutes into local tissues below a site of topical application may be estimated based on knowledge of their lipophilicity alone.

Dendritic Core-Multishell Nanocarriers in Murine Models of Healthy and Atopic Skin.

PubMed

Radbruch, Moritz; Pischon, Hannah; Ostrowski, Anja; Volz, Pierre; Brodwolf, Robert; Neumann, Falko; Unbehauen, Michael; Kleuser, Burkhard; Haag, Rainer; Ma, Nan; Alexiev, Ulrike; Mundhenk, Lars; Gruber, Achim D

2017-12-01

Dendritic hPG-amid-C18-mPEG core-multishell nanocarriers (CMS) represent a novel class of unimolecular micelles that hold great potential as drug transporters, e.g., to facilitate topical therapy in skin diseases. Atopic dermatitis is among the most common inflammatory skin disorders with complex barrier alterations which may affect the efficacy of topical treatment.Here, we tested the penetration behavior and identified target structures of unloaded CMS after topical administration in healthy mice and in mice with oxazolone-induced atopic dermatitis. We further examined whole body distribution and possible systemic side effects after simulating high dosage dermal penetration by subcutaneous injection.Following topical administration, CMS accumulated in the stratum corneum without penetration into deeper viable epidermal layers. The same was observed in atopic dermatitis mice, indicating that barrier alterations in atopic dermatitis had no influence on the penetration of CMS. Following subcutaneous injection, CMS were deposited in the regional lymph nodes as well as in liver, spleen, lung, and kidney. However, in vitro toxicity tests, clinical data, and morphometry-assisted histopathological analyses yielded no evidence of any toxic or otherwise adverse local or systemic effects of CMS, nor did they affect the severity or course of atopic dermatitis.Taken together, CMS accumulate in the stratum corneum in both healthy and inflammatory skin and appear to be highly biocompatible in the mouse even under conditions of atopic dermatitis and thus could potentially serve to create a depot for anti-inflammatory drugs in the skin.

Integrated approach in the assessment of skin compatibility of cosmetic formulations with green coffee oil.

PubMed

Wagemaker, T A L; Rijo, P; Rodrigues, L M; Maia Campos, P M B G; Fernandes, A S; Rosado, C

2015-10-01

Green coffee oil (GCO) has been used in cosmetic formulations due to its emollient and anti-ageing properties. However, there are insufficient studies about its safety when applied in cosmetic formulations. Cytotoxicity of GCO and of formulations containing 2.5-15% of GCO was evaluated by the MTT reduction assay, in human keratinocytes. Formulations containing 15% of GCO and the vehicle were applied under in use conditions in the volar forearm of human volunteers during 3 days. Transepidermal water loss, stratum corneum water content and erythema index were evaluated each 24 h using biophysical techniques. The same formulations were probed for skin tolerance through a patch test. Neither pure GCO nor its formulations showed cytotoxic effects in concentrations up to 100 μg mL(-1) . Transepidermal water loss values showed a slight reduction when the formulation containing GCO was applied. Stratum corneum water content and erythema index did not show significant differences, as the results observed in the first day of the study were maintained throughout 3 days. None of the volunteers display any reaction after using an occlusive patch. The results obtained in the study indicate that GCO seems to be safe for topical applications and showed good skin compatibility under the experimental conditions of the study. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Application of a non-invasive method to study the moisturizing effect of formulations containing vitamins A or E or ceramide on human skin.

PubMed

Leonardi, Gislaine Ricci; Gaspar, Lorena Rigo; Maia Campos, Patrícia M B G

2002-01-01

Moisturizers containing vitamins A and E as well as ceramides are believed to improve the skin condition by increasing the water content of the stratum corneum. The aim of this research was to evaluate, through the capacitance method (a non-invasive method), the moisturizing effect of an O/W emulsion (non-ionic self-emulsifying base) containing vitamin A palmitate, vitamin E acetate, and ceramide III on human skin. The studies were carried out on a group of 40 healthy Caucasian female test subjects between 30 and 45 years of age, using the Corneometer CM 825 PC. Skin measurements were taken from the volunteers at 7 and 30 days after daily use (twice a day) of the tested products. The presence of vitamins A and E or ceramide III did not cause an improvement in the hydration of the stratum corneum, which means that none of those compounds strengthens the hydration effectiveness of the base formulations used, at least at the doses tested. The interpretation of electrical measurement regarding skin moisture should be made with caution; thus the results observed in this study show the importance of using different approaches (or methodologies) to verify the performance of the formulas tested. We conclude that, at the low doses typically used in cosmetic formulations, vitamins A and E and ceramide III are not likely to contribute to the hydrating effects of the base moisturizing formulation when assessed by capacitance.

Experimental study of airflow characteristics of stratum ventilation in a multi-occupant room with comparison to mixing ventilation and displacement ventilation.

PubMed

Cheng, Y; Lin, Z

2015-12-01

The motivation of this study is stimulated by a lack of knowledge about the difference of airflow characteristics between a novel air distribution method [i.e., stratum ventilation (SV)] and conventional air distribution methods [i.e., mixing ventilation (MV) and displacement ventilation (DV)]. Detailed air velocity and temperature measurements were conducted in the occupied zone of a classroom with dimensions of 8.8 m (L) × 6.1 m (W) × 2.4 m (H). Turbulence intensity and power spectrum of velocity fluctuation were calculated using the measured data. Thermal comfort and cooling efficiency were also compared. The results show that in the occupied zone, the airflow characteristics among MV, DV, and SV are different. The turbulent airflow fluctuation is enhanced in this classroom with multiple thermal manikins due to thermal buoyancy and airflow mixing effect. Thermal comfort evaluations indicate that in comparison with MV and DV, a higher supply air temperature should be adopted for SV to achieve general thermal comfort with low draft risk. Comparison of the mean air temperatures in the occupied zone reveals that SV is of highest cooling efficiency, followed by DV and then MV. This study reports the unique profiles of flow, temperature, turbulence intensity, and power spectrum of stratum ventilation, which can have a number of implications for both knowledge and understanding of the flow characteristics in a stratum-ventilated room. With respect to the former, it expounds the fundamental characteristics of this air distribution method; and with respect to the latter, it reveals the mechanism of thermal comfort and energy saving under stratum ventilation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Tricky Tear Trough

PubMed Central

Belden, Sarah; Miller, Richard A.

2015-01-01

There is a growing demand for noninvasive anti-aging products for which the periorbital region serves as a critical aspect of facial rejuvenation. This article reviews a multitude of cosmeceutical ingredients that have good scientific data, specifically for the periorbital region. Topical treatment options have exponentially grown from extensively studied retinoids, to recently developed technology, such as growth factors and peptides. With a focus on the periorbital anatomy, the authors review the mechanisms of action of topical cosmeceutical ingredients, effectiveness of ingredient penetration through the stratum corneum, and validity of clinical trials. PMID:26430490

Pitted keratolysis*

PubMed Central

de Almeida Jr, Hiram Larangeira; Siqueira, Rodrigo Nunes; Meireles, Renan da Silva; Rampon, Greice; de Castro, Luis Antonio Suita; Silva, Ricardo Marques e

2016-01-01

Pitted keratolysis is a skin disorder that affects the stratum corneum of the plantar surface and is caused by Gram-positive bacteria. A 30-year-old male presented with small punched-out lesions on the plantar surface. A superficial shaving was carried out for scanning electron microscopy. Hypokeratosis was noted on the plantar skin and in the acrosyringium, where the normal elimination of corneocytes was not seen. At higher magnification (x 3,500) bacteria were easily found on the surface and the described transversal bacterial septation was observed. PMID:26982791

Skin fluorescence model based on the Monte Carlo technique

NASA Astrophysics Data System (ADS)

Churmakov, Dmitry Y.; Meglinski, Igor V.; Piletsky, Sergey A.; Greenhalgh, Douglas A.

2003-10-01

The novel Monte Carlo technique of simulation of spatial fluorescence distribution within the human skin is presented. The computational model of skin takes into account spatial distribution of fluorophores following the collagen fibers packing, whereas in epidermis and stratum corneum the distribution of fluorophores assumed to be homogeneous. The results of simulation suggest that distribution of auto-fluorescence is significantly suppressed in the NIR spectral region, while fluorescence of sensor layer embedded in epidermis is localized at the adjusted depth. The model is also able to simulate the skin fluorescence spectra.

Acral Peeling Skin Syndrome Resembling Epidermolysis Bullosa Simplex in a 10-Month-Old Boy

PubMed Central

Kavaklieva, S.; Yordanova, I.; Bruckner-Tuderman, L.; Has, C.

2013-01-01

The acral peeling skin syndrome (APSS) is a rare autosomal recessive disorder clinically characterized by asymptomatic desquamation of the skin limited to the hands and feet and histologically by cleavage at the stratum granulosum and stratum corneum level [Kiritsi et al.: J Invest Dermatol 2010;130:1741–1746]. We report on a 10-month-old boy with a history of skin peeling limited to the hands and feet since 2 months of age. Clinical examination revealed erythematous erosions with peripheral desquamation and flaccid blisters. DNA mutation analysis detected two heterozygous TGM5 mutations: c.2T>C, p.M1T in exon 1 and c.337G>T, p.G113C in exon 3 in keeping with the diagnosis of APSS. The clinical presentation of APSS alone might be confusing and strongly resemble epidermolysis bullosa simplex making the differential diagnosis difficult. PMID:24019772

Formulation and characterization of liquid crystal systems containing azelaic acid for topical delivery.

PubMed

Aytekin, Merve; Gursoy, R Neslihan; Ide, Semra; Soylu, Elif H; Hekimoglu, Sueda

2013-02-01

The aim of this study is to prepare and characterize azelaic acid (AzA) containing liquid crystal (LC) drug delivery systems for topical use. Two ternary phase diagrams, containing liquid paraffin as the oil component and a mixture of two nonionic surfactants (Brij 721P and Brij 72), were constructed. Formulations chosen from the phase diagrams were characterized by polarized light microscopy, rheological analyses, differential scanning calorimetry (DSC), and small angle x-ray scattering spectroscopy. Polarized light microscopy proved that except the oil/water emulsion (O/W E), other formulations showed lamellar LC structure. In vitro release studies indicated that the fastest release was achieved by the Lamellar LC (LLC) and O/W E systems, whereas slower release was obtained from the emulsion containing lamellar LC (E-LLC) and distorted lamellar LC (D-LLC) systems. Results of rheological measurements both supported the results of in vitro release studies and showed that the emulsion containing the LC (E-LLC) system had the most stable structure. The formulations and their effect on stratum corneum (SC) were evaluated by DSC studies. The lamellar LC (LLC), emulsion containing lamellar liquid crystal (E-LLC), and O/W E formulations had an effect on both lipid and protein components of SC, whereas distorted lamellar liquid crystal (D-LLC) system had an effect on only the lipid components of SC. LLC systems could be considered promising for the topical delivery of AzA.

Transdermal Protein Delivery Using Choline and Geranate (CAGE) Deep Eutectic Solvent.

PubMed

Banerjee, Amrita; Ibsen, Kelly; Iwao, Yasunori; Zakrewsky, Michael; Mitragotri, Samir

2017-08-01

Transdermal delivery of peptides and other biological macromolecules is limited due to skin's inherent low permeability. Here, the authors report the use of a deep eutectic solvent, choline and geranate (CAGE), to enhance topical delivery of proteins such as bovine serum albumin (BSA, molecular weight: ≈66 kDa), ovalbumin (OVA, molecular weight: ≈45 kDa) and insulin (INS, molecular weight: 5.8 kDa). CAGE enhances permeation of BSA, OVA, and insulin into porcine skin ex vivo, penetrating deep into the epidermis and dermis. Studies using tritium-labeled BSA and fluorescein isothiocyanate labeled insulin show significantly enhanced delivery of proteins into and across porcine skin, penetrating the skin in a time-dependent manner. Fourier transform IR spectra of porcine stratum corneum (SC) samples before and after incubation in CAGE show a reduction in peak area attributed to SC lipid content, suggesting lipid extraction from the SC. Circular dichroism confirms that CAGE does not affect insulin's secondary conformation. In vivo studies in rats show that topical application of 10 U insulin dispersed in CAGE (25 U kg -1 insulin dose) leads to a highly significant 40% drop in blood glucose levels in 4 h that is relatively sustained for 12 h. Taken together, these studies demonstrate that CAGE is a promising vehicle for transdermal delivery of therapeutic proteins; specifically, as a noninvasive delivery alternative to injectable insulin for the treatment of diabetes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Estimators used in the New Mexico inventory: practical implications of "truly" random nonresponse within each stratum

Treesearch

Paul L. Patterson; Sara A. Goeking

2012-01-01

The annual forest inventory of New Mexico began as an accelerated inventory, and 8 of the 10 Phase 2 panels were sampled between 2008 and 2011. The inventory includes a large proportion of nonresponse. FIA's estimation process uses post-stratification and assumes that nonresponse occurs at random within each stratum. We construct an estimator for the New Mexico...

Increased transepidermal water loss and decreased ceramide content in lesional and non-lesional skin of dogs with atopic dermatitis.

PubMed

Shimada, Kenichiro; Yoon, Ji-Seon; Yoshihara, Toru; Iwasaki, Toshiroh; Nishifuji, Koji

2009-10-01

This study evaluated changes in transepidermal water loss (TEWL), skin hydration and intercorneal lipid content in dogs with atopic dermatitis (AD). TEWL and skin hydration were measured in the inguinal skin of 10 dogs with AD and 30 normal dogs. TEWL was significantly higher in both lesional skin (94.3 +/- 38.8 g/m(2)/h) and non-lesional skin (28.8 +/- 9.5) of dogs with AD than healthy controls (12.3 +/- 2.3) (P < 0.05). Water content in the lesional skin of dogs with AD (15.8 +/- 7.0 AU) was significantly lower than that of controls (24.2 +/- 8.8) (P < 0.05), whereas no significant differences were recognized in water content between non-lesional skin of dogs with AD and controls. To compare the lipid content between lesional and non-lesional skin of dogs with AD and controls, intercorneal lipids, extracted from the stratum corneum, were quantified by thin-layer chromatography. The relative amounts of ceramides in the lesional skin (24.4 +/- 5.6%) and non-lesional skin (25.6 +/- 3.8%) of dogs with AD were significantly lower than those in controls (31.4 +/- 6.9%) (P < 0.05). Conversely, no significant differences were recognized in the relative amounts of cholesterols and free fatty acids (FFA) between dogs with AD and controls. Moreover, there are statistical correlations between TEWL and the relative amounts of ceramides, but not those of cholesterols and FFA, in both lesional and non-lesional skin of dogs with AD. These results strongly suggest that decreased ceramide content accelerates TEWL in dogs with AD, similar to the situation seen in the corresponding human disease.

Dry skin (xerosis) in patients undergoing maintenance haemodialysis: the role of decreased sweating of the eccrine sweat gland.

PubMed

Park, T H; Park, C H; Ha, S K; Lee, S H; Song, K S; Lee, H Y; Han, D S

1995-12-01

The aetiology and the pathophysiological mechanisms underlying the development of dry skin in uraemia are still unclear, but the hydration status of stratum corneum clearly influences the appearance of skin. The xerotic skin texture is often referred to as 'dry skin' and has been suggested as a cause of uraemic pruritus. To understand the aetiology of dry skin in uraemia we measured the status of skin surface hydration of uraemic patients with the corneometer and skin surface hydrometer, the functional capacity and the urea concentration of stratum corneum and the response of eccrine sweat gland to sudorific agent (0.05% pilocarpine HCL) in 18 age-matched haemodialysis patients and 10 healthy volunteers. We also performed the water sorption-desorption test to uraemic and control subjects after application of urea in various concentrations. Uraemic patient's skin showed decreased water content compared to control subjects. However, we found no correlation between dry skin and pruritus. Although the urea concentration of the horny layer in uraemic patients was elevated compared to control subjects (28.2 microgram/cm2 vs 5.04 micrograms/cm2, P < 0.05), its moisturizing effect to relieve pruritus is questionable because its artificial application revealed no improvement of the functional capacity of horny layer in concentration 5 times higher than the physiological concentration. Uraemic patients showed decreased sweating response to sudorific agent. In conclusion, the functional abnormalities of eccrine sweat glands may be account for dry skin in uraemic patients at least in part, but there is no correlation between xerosis and pruritus.

Topical application of nanoparticles: prospects and safety aspects (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lademann, Jürgen M.; Richter, Heike; Jung, Sora; Meinke, Martina C.; Rühl, Eckart; Alexiev, Ulrike; Calderon, Marcelo; Patzelt, Alexa

2016-03-01

The requirements on nanoparticles for cosmetic and medical applications are very different. While nanoparticles applied in sunscreens shall remain on the skin surface or in the upper cell layers of the stratum corneum, nanoparticles for medical drug delivery shall penetrate through the skin barrier to the target structures in the living cells. Under the Collaborative Research Project 1112 various methods are used at the CCP to investigate the cutaneous penetration and storage of nanoparticles, hair follicles being in the focus of attention. Human hair follicles are ideal target structures for drug delivery. Hosting both the stem and dendritic cells, they are surrounded by a dense network of blood vessels. Investigating nanoparticles of different size and materials, particles of approximately 600 nm in diameter were found to penetrate best into the hair follicles, where they can be stored for maximally 10 days. Their retention time in the hair follicles exceeds that in the stratum corneum by almost one order of magnitude. Particles penetrate more efficiently into the hair follicles than non-particulate substances. For particles from 40 nm-1 µm in diameter, however, no follicular penetration has been detectable if the skin barrier was intact. This is plausible as the hair follicle has its own barrier. It will be demonstrated that the best way for drug delivery is the application of drug-loaded particulate carrier systems. In the hair follicles the particles may either dissolve and release the drug, or an external signal must trigger the drug release from the particle.

Assessment of an extended dataset of in vitro human dermal absorption studies on pesticides to determine default values, opportunities for read-across and influence of dilution on absorption.

PubMed

Aggarwal, M; Fisher, P; Hüser, A; Kluxen, F M; Parr-Dobrzanski, R; Soufi, M; Strupp, C; Wiemann, C; Billington, R

2015-06-01

Dermal absorption is a key parameter in non-dietary human safety assessments for agrochemicals. Conservative default values and other criteria in the EFSA guidance have substantially increased generation of product-specific in vitro data and in some cases, in vivo data. Therefore, data from 190 GLP- and OECD guideline-compliant human in vitro dermal absorption studies were published, suggesting EFSA defaults and criteria should be revised (Aggarwal et al., 2014). This follow-up article presents data from an additional 171 studies and also the combined dataset. Collectively, the data provide consistent and compelling evidence for revision of EFSA's guidance. This assessment covers 152 agrochemicals, 19 formulation types and representative ranges of spray concentrations. The analysis used EFSA's worst-case dermal absorption definition (i.e., an entire skin residue, except for surface layers of stratum corneum, is absorbed). It confirmed previously proposed default values of 6% for liquid and 2% for solid concentrates, irrespective of active substance loading, and 30% for all spray dilutions, irrespective of formulation type. For concentrates, absorption from solvent-based formulations provided reliable read-across for other formulation types, as did water-based products for solid concentrates. The combined dataset confirmed that absorption does not increase linearly beyond a 5-fold increase in dilution. Finally, despite using EFSA's worst-case definition for absorption, a rationale for routinely excluding the entire stratum corneum residue, and ideally the entire epidermal residue in in vitro studies, is presented. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Characterization of oily mature skin by biophysical and skin imaging techniques.

PubMed

de Melo, M O; Maia Campos, P M B G

2018-02-13

The skin is a complex biological system and may suffer change according to the environmental factors, as higher temperatures can increase sebum excretion, presenting oiliness and acne. These alterations can persist during the aging and provoke more changes in aged skin. In this study we evaluated the mature oily skin characteristics using biophysical and skin imaging techniques. Sixty healthy female subjects, aged between 39 and 55 years old were recruited and separated into 2 groups according to their skin type: normal/dry and oily skin. The skin was evaluated in terms of stratum corneum water content, transepidermal water loss (TEWL) sebum content, dermis thickness and echogenicity, skin microrelief, and pores content. The mature oily skin presented no significant differences when compared to the normal/dry skin on the stratum corneum water content and TEWL parameters. The sebum content was significantly higher on the oily skin group. The microrelief analysis showed an increase of skin roughness values in the oily skin and increase of scaliness in the normal/dry skin. The oily skin showed lower dermis echogenicity mainly in the frontal region and higher dermis thickness when compared to normal/dry skin. The mature oily skin showed different characteristics from normal/dry skin in terms of sebum content, microrelief parameters, and dermis thickness. This way, the characterization of mature oily skin in an objective way is very important to development of dermocosmetic products for more effective treatments focused specially on this type of skin. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The irritation potential and reservoir effect of mild soaps.

PubMed

Lodén, Marie; Buraczewska, Izabela; Edlund, Fredrik

2003-08-01

Identification and reduction of external noxious factors is one key point in the strategy for the treatment and reduction of contact dermatitis. A wide variety of soaps on the market are claimed to be suitable for the use on sensitive skin due to their mildness. The aim of the present study was to illustrate possible differences in the irritation potential of 8 products and to investigate whether surfactant residues may form an irritant reservoir on the skin. The study was double-blind, randomized using healthy human volunteers. The inherent capacity of the products to induce irritation was determined using conventional patch test technique, whereas detection of potential surfactant residues on the skin was done using a methodology developed in the 1960s for detection of the corticosteroid reservoir in the stratum corneum. The method comprised the release of active substance from the stratum corneum reservoir by occlusion of the skin with an aluminium chamber, followed by evaluation of the biological response. In the present study, the soap-treated area was rinsed with water and then occluded. Instrumental measurements of the transepidermal water loss and superficial skin blood flow served as indicators of the injurious effects of the products. The results showed large differences in irritation potential between the products, and some of them demonstrated considerable damaging effect. Moreover, the study proved the presence of barrier-impairing residues on the skin after rinsing with water. Subclinical skin damage can make the skin vulnerable to further irritation and delay recovery of chronic irritant contact dermatitis.

Lowering relative humidity level increases epidermal protein deimination and drives human filaggrin breakdown.

PubMed

Cau, Laura; Pendaries, Valérie; Lhuillier, Emeline; Thompson, Paul R; Serre, Guy; Takahara, Hidenari; Méchin, Marie-Claire; Simon, Michel

2017-05-01

Deimination (also known as citrullination), the conversion of arginine in a protein to citrulline, is catalyzed by a family of enzymes called peptidylarginine deiminases (PADs). Three PADs are expressed in the epidermis, one of their targets being filaggrin. Filaggrin plays a central role in atopic dermatitis and is a key protein for the epidermal barrier. It aggregates keratins and is cross-linked to cornified envelopes. Following its deimination, it is totally degraded to release free amino acids, contributing to the natural moisturizing factor (NMF). The mechanisms controlling this multistep catabolism in human are unknown. To test whether external humidity plays a role, and investigate the molecular mechanisms involved. Specimens of reconstructed human epidermis (RHEs) produced in humid or dry conditions (>95% or 30-50% relative humidity) were compared. RHEs produced in the dry condition presented structural changes, including a thicker stratum corneum and a larger amount of keratohyalin granules. The transepidermal water loss and the stratum corneum pH were decreased whereas the quantity of NMF was greater. This highly suggested that filaggrin proteolysis was up-regulated. The expression/activity of the proteases involved in filaggrin breakdown did not increase while PAD1 expression and the deimination rate of proteins, including filaggrin, were drastically enhanced. Partial inhibition of PADs with Cl-amidine reversed the effect of dryness on filaggrin breakdown. These results demonstrate the importance of external humidity in the control of human filaggrin metabolism, and suggest that deimination plays a major role in this regulation. Copyright © 2017 Japanese Society for Investigative Dermatology. All rights reserved.

Does dietary fluid intake affect skin hydration in healthy humans? A systematic literature review.

PubMed

Akdeniz, M; Tomova-Simitchieva, T; Dobos, G; Blume-Peytavi, U; Kottner, J

2018-02-02

Associations between daily amounts of drinking water and skin hydration and skin physiology receive increasingly attention in the daily life and in clinical practice. However, there is a lack of evidence of dermatological benefits from drinking increased amounts of water. Pubmed and Web of Science were searched without any restrictions of publication dates. References of included papers and related reviews were checked. Eligibility criteria were primary intervention and observational studies investigating the effects of fluid intake on skin properties in English, German, Spanish or Portuguese language, including subjects being healthy and 18+ years. Searches resulted in 216 records, 23 articles were read in full text, and six were included. The mean age of the samples ranged from 24 to 56 years. Overall the evidence is weak in terms of quantity and methodological quality. Disregarding the methodological limitations a slight increase in stratum corneum and "deep" skin hydration was observed after additional water intake, particularly in individuals with lower prior water consumption. Reductions of clinical signs of dryness and roughness were observed. The extensibility and elasticity of the skin increased slightly. Unclear associations were shown between water intake and transepidermal water loss, sebum content, and skin surface pH. Additional dietary water intake may increase stratum corneum hydration. The underlying biological mechanism for this possible relationship is unknown. Whether this association also exists in aged subjects is unclear. Research is needed to answer the question whether increased fluid intake decreases signs of dry skin. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Improvement of skin conditions by ingestion of Aspergillus kawachii (Koji) extract containing 14-dehydroergosterol in a randomized, double-blind, controlled trial.

PubMed

Sugihara, Yoshihiko; Ikushima, Shigehito; Miyake, Mika; Kirisako, Takayoshi; Yada, Yukihiro; Fujiwara, Daisuke

2018-01-01

The present study examined the effect of ingestion of Koji extract containing 14-dehydroergosterol (14-DHE), prepared from Aspergillus kawachii NBRC4308, on improvement of skin conditions among healthy volunteers. In a randomized, double-blind, placebo-controlled, parallel-group study, 70 healthy adult women who felt that their skin was dry ingested either a placebo dietary supplement or Koji extract (200 mg/day) supplement containing 0.1% 14-DHE for 12 weeks. Throughout the treatment period and for 4 weeks afterward, objective indicators - including moisture content of the stratum corneum, trans-epidermal water loss (TEWL), and skin wrinkles - were evaluated; in addition, the subjects answered a questionnaire on their skin conditions with ratings on a visual analog scale. Statistical analysis was conducted on the basis of differences from baseline scores. Compared with the placebo group, the Koji extract group showed significantly increased forearm moisture at 4, 8, and 16 weeks ( p < 0.05 on unpaired t -test). The questionnaire survey showed a marked improvement in skin conditions, particularly crow's feet, in the Koji extract group versus the placebo group at 8 weeks ( p < 0.05 by unpaired t -test). Furthermore, the Koji extract group showed a trend ( p < 0.10) toward improvement in skin moisture (at 4 weeks), dryness around the eyes/mouth (at 4 weeks), and overall skin condition (at 8 weeks) versus the placebo group. Ingestion of Koji extract containing 14-DHE was demonstrated to have positive effects toward improving skin conditions - in particular, on increasing skin moisture in the stratum corneum.

The revised EEMCO guidance for the in vivo measurement of water in the skin.

PubMed

Berardesca, Enzo; Loden, Marie; Serup, Jorgen; Masson, Philippe; Rodrigues, Luis Monteiro

2018-06-20

Noninvasive quantification of stratum corneum water content is widely used in skin research and topical product development. The original EEMCO guidelines on measurements of skin hydration by electrical methods and transepidermal water loss (TEWL) by evaporimeter published in 1997 and 2001 have been revisited and updated with the incorporation of recently available technologies. Electrical methods and open-chamber evaporimeters for measurement of TEWL are still the preferred techniques to measure the water balance in the stratum corneum. The background technology and biophysics of these instruments remain relevant and valid. However, new methods that can image surface hydration and measure depth profiles of dermal water content now available. Open-chamber measurement of TEWL has been supplemented with semiopen and closed chamber probes, which are more robust to environmental influence and therefore convenient to use and more applicable to field studies. However, closed chamber methods interfere with the evaporation of water, and the methods cannot be used for continuous monitoring. Validation of methods with respect to intra- and inter-instrument variation remains challenging. No validation standard or test phantom is available. The established methods for measurement of epidermal water content and TEWL have been supplemented with important new technologies including methods that allow imaging of epidermal water distribution and water depth profiles. A much more complete and sophisticated characterization of the various aspects of the dermal water barrier has been accomplished by means of today's noninvasive techniques; however, instrument standardization and validation remain a challenge. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hydrogel-forming Microneedle Arrays Exhibit Antimicrobial Properties: Potential for Enhanced Patient Safety

PubMed Central

Donnelly, Ryan F.; Singh, Thakur Raghu Raj; Alkilani, Ahlam Zaid; McCrudden, Maelíosa T.C.; O’Mahony, Conor; Armstrong, Keith; McLoone, Nabla; Kole, Prashant; Woolfson, A. David

2014-01-01

We describe, for the first time, the microbial characterisation of hydrogel-forming polymeric microneedle arrays and the potential for passage of microorganisms into skin following microneedle penetration. Uniquely, we also present insights into the storage stability of these hydroscopic formulations, from physical and microbiological viewpoints, and examine clinical performance and safety in human volunteers. Experiments employing excised porcine skin and radiolabelled microorganisms showed that microorganisms can penetrate skin beyond the stratum corneum following microneedle puncture. Indeed, the numbers of microorganisms crossing the stratum corneum following microneedle puncture was greater than 105 cfu in each case. However, no microorganisms crossed the epidermal skin. When using a 21G hypodermic needle, more than 104 microorganisms penetrated into the viable tissue and 106 cfu of C. albicans and S. epidermidis completely crossed the epidermal skin in 24 h. The hydrogel-forming materials contained no microorganisms following de-moulding and exhibited no microbial growth during storage, while also maintaining their mechanical strength, apart from when stored at relative humidities of 86%. No microbial penetration through the swelling microneedles was detectable, while human volunteer studies confirmed that skin or systemic infection is highly unlikely when polymeric microneedles are used for transdermal drug delivery. Since no pharmacopoeial standards currently exist for microneedle-based products, the exact requirements for a proprietary product based on hydrogel-forming microneedles are at present unclear. However, we are currently working towards a comprehensive specification set for this microneedle system that may inform future developments in this regard. PMID:23644043

Softness sensor system for simultaneously measuring the mechanical properties of superficial skin layer and whole skin.

PubMed

Nakatani, Masashi; Fukuda, Toru; Arakawa, Naomi; Kawasoe, Tomoyuki; Omata, Sadao

2013-02-01

Few attempts have been made to distinguish the softness of different skin layers, though specific measurement of the superficial layer would be useful for evaluating the emollient effect of cosmetics and for diagnosis of skin diseases. We developed a sensor probe consisting of a piezoelectric tactile sensor and a load cell. To evaluate it, we firstly measured silicone rubber samples with different softness. Then, it was applied to human forearm skin before and after tape-stripping. A VapoMeter and skin-surface hygrometer were used to confirm removal of the stratum corneum. A Cutometer was used to obtain conventional softness data for comparison. Both the piezoelectric tactile sensor and the load cell could measure the softness of silicone rubber samples, but the piezoelectric tactile sensor was more sensitive than the load cell when the reaction force of the measured sample was under 100 mN in response to a 2-mm indentation. For human skin in vivo, transepidermal water loss and skin conductance were significantly changed after tape-stripping, confirming removal of the stratum corneum. The piezoelectric tactile sensor detected a significant change after tape-stripping, whereas the load cell did not. Thus, the piezoelectric tactile sensor can detect changes of mechanical properties at the skin surface. The load cell data were in agreement with Cutometer measurements, which showed no change in representative skin elasticity parameters after tape-stripping. These results indicate that our sensor can simultaneously measure the mechanical properties of the superficial skin layer and whole skin. © 2012 John Wiley & Sons A/S.

Topical delivery of a preformed photosensitizer for photodynamic therapy of cutaneous lesions

NASA Astrophysics Data System (ADS)

Oleinick, Nancy L.; Kenney, Malcolm E.; Lam, Minh; McCormick, Thomas; Cooper, Kevin D.; Baron, Elma D.

2012-02-01

Photosensitizers for photodynamic therapy (PDT) are most commonly delivered to patients or experimental animals via intravenous injection. After initial distribution throughout the body, there can be some preferential accumulation within tumors or other abnormal tissue in comparison to the surrounding normal tissue. In contrast, the photosensitizer precursor, 5-aminolevulinic acid (ALA) or one of its esters, is routinely administered topically, and more specifically, to target skin lesions. Following metabolic conversion to protoporphyrin IX, the target area is photoilluminated, limiting peripheral damage and targeting the effective agent to the desired region. However, not all skin lesions are responsive to ALA-PDT. Topical administration of fully formed photosensitizers is less common but is receiving increased attention, and some notable advances with selected approved and experimental photosensitizers have been published. Our team has examined topical administration of the phthalocyanine photosensitizer Pc 4 to mammalian (human, mouse, pig) skin. Pc 4 in a desired formulation and concentration was applied to the skin surface at a rate of 5-10 μL/cm2 and kept under occlusion. After various times, skin biopsies were examined by confocal microscopy, and fluorescence within regions of interest was quantified. Early after application, images show the majority of the Pc 4 fluorescence within the stratum corneum and upper epidermis. As a function of time and concentration, penetration of Pc 4 across the stratum corneum and into the epidermis and dermis was observed. The data indicate that Pc 4 can be delivered to skin for photodynamic activation and treatment of skin pathologies.

Experimental investigation into the interaction between the human body and room airflow and its effect on thermal comfort under stratum ventilation.

PubMed

Cheng, Y; Lin, Z

2016-04-01

Room occupants' comfort and health are affected by the airflow. Nevertheless, they themselves also play an important role in indoor air distribution. This study investigated the interaction between the human body and room airflow under stratum ventilation. Simplified thermal manikin was employed to effectively resemble the human body as a flow obstacle and/or free convective heat source. Unheated and heated manikins were designed to fully evaluate the impact of the manikin at various airflow rates. Additionally, subjective human tests were conducted to evaluate thermal comfort for the occupants in two rows. The findings show that the manikin formed a local blockage effect, but the supply airflow could flow over it. With the body heat from the manikin, the air jet penetrated farther compared with that for the unheated manikin. The temperature downstream of the manikin was also higher because of the convective effect. Elevating the supply airflow rate from 7 to 15 air changes per hour varied the downstream airflow pattern dramatically, from an uprising flow induced by body heat to a jet-dominated flow. Subjective assessments indicated that stratum ventilation provided thermal comfort for the occupants in both rows. Therefore, stratum ventilation could be applied in rooms with occupants in multiple rows. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Tinea versicolor, tinea nigra, white piedra, and black piedra.

PubMed

Bonifaz, Alexandro; Gómez-Daza, Fernando; Paredes, Vanessa; Ponce, Rosa María

2010-03-04

Superficial mycoses are fungal infections limited to the stratum corneum and its adnexal structures. The most frequent types are dermatophytoses or tineas. Tinea versicolor involves the skin in the form of hypochromic or hyperchromic plaques, and tinea nigra affects the skin of the palms with dark plaques. White piedra and black piedra are parasitic infections of scalp hairs in the form of concretions caused by fungal growth. Diagnosis of these mycoses is made from mycologic studies, direct examination, stains, and isolation, and identification of the fungi. Treatment includes systemic antifungals, topical antifungals, and keratolytics. Copyright 2010 Elsevier Inc. All rights reserved.

Analysis of skin tissues spatial fluorescence distribution by the Monte Carlo simulation

NASA Astrophysics Data System (ADS)

Y Churmakov, D.; Meglinski, I. V.; Piletsky, S. A.; Greenhalgh, D. A.

2003-07-01

A novel Monte Carlo technique of simulation of spatial fluorescence distribution within the human skin is presented. The computational model of skin takes into account the spatial distribution of fluorophores, which would arise due to the structure of collagen fibres, compared to the epidermis and stratum corneum where the distribution of fluorophores is assumed to be homogeneous. The results of simulation suggest that distribution of auto-fluorescence is significantly suppressed in the near-infrared spectral region, whereas the spatial distribution of fluorescence sources within a sensor layer embedded in the epidermis is localized at an `effective' depth.

[Scabies in childhood and adolescence].

PubMed

Fölster-Holst, R; Sunderkötter, C

2016-12-01

Scabies is a common parasitosis, occurring worldwide and at any age that impairs the quality of life of patients and their families by the itching and the stigmatization. The main aims of therapy are destroying the mites Sarcoptes scabiei var. hominis that infect the stratum corneum and reduction of the itching. This requires detailed clarification for the patients and the parents of affected children as the instructions for the use of the drugs and also the necessary additional steps are often not correctly followed. Many special features regarding the clinical symptoms and therapy in early childhood should be taken into consideration.

Anatomy of the Skin and the Pathogenesis of Nonmelanoma Skin Cancer.

PubMed

Losquadro, William D

2017-08-01

Skin is composed of the epidermis, dermis, and adnexal structures. The epidermis is composed of 4 layers-the stratums basale, spinosum, granulosum, and corneum. The dermis is divided into a superficial papillary dermis and deeper reticular dermis. Collagen and elastin within the reticular dermis are responsible for skin tensile strength and elasticity, respectively. The 2 most common kinds of nonmelanoma skin cancers are basal cell and squamous cell carcinoma. Both are caused by a host of environmental and genetic factors, although UV light exposure is the single greatest predisposing factor. Copyright © 2017 Elsevier Inc. All rights reserved.

The barrier function of organotypic non-melanoma skin cancer models.

PubMed

Zoschke, Christian; Ulrich, Martina; Sochorová, Michaela; Wolff, Christopher; Vávrová, Kateřina; Ma, Nan; Ulrich, Claas; Brandner, Johanna M; Schäfer-Korting, Monika

2016-07-10

Non-melanoma skin cancer (NMSC) is the most frequent human cancer with continuously rising incidences worldwide. Herein, we investigated the molecular basis for the impaired skin barrier function of organotypic NMSC models. We unraveled disturbed epidermal differentiation by reflectance confocal microscopy and histopathological evaluation. While the presence of claudin-4 and occludin were distinctly reduced, zonula occludens protein-1 was more wide-spread, and claudin-1 was heterogeneously distributed within the NMSC models compared with normal reconstructed human skin. Moreover, the cancer altered stratum corneum lipid packing and profile with decreased cholesterol content, increased phospholipid amount, and altered ceramide subclasses. These alterations contributed to increased surface pH and to 1.5 to 2.6-fold enhanced caffeine permeability of the NMSC models. Three topical applications of ingenol mebutate gel (0.015%) caused abundant epidermal cell necrosis, decreased Ki-67 indices, and increased lactate dehydrogenase activity. Taken together, our study provides new biological insights into the microenvironment of organotypic NMSC models, improves the understanding of the disease model by revealing causes for impaired skin barrier function in NMSC models at the molecular level, and fosters human cell-based approaches in preclinical drug evaluation. Copyright © 2016 Elsevier B.V. All rights reserved.

Rat epidermal keratinocyte organotypic culture (ROC) compared to human cadaver skin: the effect of skin permeation enhancers.

PubMed

Pappinen, Sari; Tikkinen, Sanna; Pasonen-Seppänen, Sanna; Murtomäki, Lasse; Suhonen, Marjukka; Urtti, Arto

2007-03-01

The objective of this study was to evaluate the response of the rat epidermal keratinocyte organotypic culture (ROC) to permeation enhancers, and to compare these responses to those in human cadaver skin. Different concentrations of two mixtures for enhancing permeation were investigated, sodium dodecyl sulfate:phenyl piperazine and methyl pyrrolidone:dodecyl pyridinium chloride, using skin impedance spectroscopy and two experimental compounds, the lipophilic corticosterone and the hydrophilic sucrose. The chemical irritation effects of the formulations were evaluated based on leakage of lactate dehydrogenase enzyme (LDH) and cellular morphological perturbation. This study provides evidence for direct correlations of permeation/permeation, impedance/impedance and permation/impedance between the culture model and human skin. The only exception was the enhancer induced permeation of sucrose which was 1-40-fold higher in ROC compared to human skin, reflecting the more disordered lipid organization in stratum corneum and consequently the greater number of polar pathways. LDH leakage and cellular morphology indicated that it was possible to differentiate between safe permeation enhancers from irritating agents. This is not only the first study to have compared the enhancer effects on a cultured skin model with human skin, but also it has demonstrated enhancer induced irritation using an artificial skin model.

Urea uptake enhances barrier function and antimicrobial defense in humans by regulating epidermal gene expression

PubMed Central

Grether-Beck, Susanne; Felsner, Ingo; Brenden, Heidi; Kohne, Zippora; Majora, Marc; Marini, Alessandra; Jaenicke, Thomas; Rodriguez-Martin, Marina; Trullas, Carles; Hupe, Melanie; Elias, Peter M.; Krutmann, Jean

2012-01-01

Urea is an endogenous metabolite, known to enhance stratum corneum hydration. Yet, topical urea anecdotally also improves permeability barrier function, and it appears to exhibit antimicrobial activity. Hence, we hypothesized that urea is not merely a passive metabolite, but a small-molecule regulator of epidermal structure and function. In 21 human volunteers, topical urea improved barrier function in parallel with enhanced antimicrobial peptide (LL-37 and β-defensin-2) expression. Urea both stimulates expression of, and is transported into keratinocytes by two urea transporters, UT-A1 and UT-A2, and by aquaporin 3, 7 and 9. Inhibitors of these urea transporters block the downstream biological effects of urea, which include increased mRNA and protein levels for: (i) transglutaminase-1, involucrin, loricrin and filaggrin; (ii) epidermal lipid synthetic enzymes, and (iii) cathelicidin/LL-37 and β-defensin-2. Finally, we explored the potential clinical utility of urea, showing that topical urea applications normalized both barrier function and antimicrobial peptide expression in a murine model of atopic dermatitis (AD). Together, these results show that urea is a small-molecule regulator of epidermal permeability barrier function and antimicrobial peptide expression after transporter uptake, followed by gene regulatory activity in normal epidermis, with potential therapeutic applications in diseased skin. PMID:22418868

Newborn infant skin: physiology, development, and care.

PubMed

Visscher, Marty O; Adam, Ralf; Brink, Susanna; Odio, Mauricio

2015-01-01

Infant skin is critical to the newborn child's transition from the womb environment to the journey to self-sufficiency. This review provides an integrative perspective on the skin development in full term and premature infants. There is a particular focus on the role of vernix caseosa and on the implications of skin development for epidermal penetration of exogenous compounds. Healthy full-term newborn skin is well-developed and functional at birth, with a thick epidermis and well-formed stratum corneum (SC) layers. Transepidermal water loss is very low at birth, equal to, or lower than adults, indicating a highly effective skin barrier. Vernix facilitates SC development in full-term infants through a variety of mechanisms including physical protection from amniotic fluid and enzymes, antimicrobial effects, skin surface pH lowering, provision of lipids, and hydration. Premature infants, particularly those of very low birth weight, have a poor skin barrier with few cornified layers and deficient dermal proteins. They are at increased risk for skin damage, increased permeability to exogenous agents and infection. The SC barrier develops rapidly after birth but complete maturation requires weeks to months. The best methods for caring for infant skin, particularly in the diaper region, are described and related to these developmental changes. Copyright © 2015 Elsevier Inc. All rights reserved.

Fluvastatin as a micropore lifetime enhancer for sustained delivery across microneedle-treated skin.

PubMed

Ghosh, Priyanka; Brogden, Nicole K; Stinchcomb, Audra L

2014-02-01

Microneedles (MNs), a physical skin permeation enhancement technique, facilitate drug delivery across the skin, thus enhancing the number of drugs that can be delivered transdermally in therapeutically relevant concentrations. The micropores created in the skin by MNs reseal because of normal healing processes of the skin, thus limiting the duration of the drug delivery window. Pore lifetime enhancement strategies can increase the effectiveness of MNs as a drug delivery mechanism by prolonging the delivery window. Fluvastatin (FLU), a HMGCoA reductase inhibitor, was used in this study to enhance the pore lifetime by inhibiting the synthesis of cholesterol, a major component of the stratum corneum lipids. The study showed that using FLU as a pretreatment it is possible to enhance the pore lifetime of MN-treated skin and thus allow for sustained drug delivery. The skin recovered within a 30-45-min time period following the removal of occlusion, and there was no significant irritation observed due to the treatment compared to the control sites. Thus, it can be concluded that localized skin treatment with FLU can be used to extend micropore lifetime and deliver drugs for up to 7 days across MN-treated skin. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

SAMPA: A free software tool for skin and membrane permeation data analysis.

PubMed

Bezrouk, Aleš; Fiala, Zdeněk; Kotingová, Lenka; Krulichová, Iva Selke; Kopečná, Monika; Vávrová, Kateřina

2017-10-01

Skin and membrane permeation experiments comprise an important step in the development of a transdermal or topical formulation or toxicological risk assessment. The standard method for analyzing these data relies on the linear part of a permeation profile. However, it is difficult to objectively determine when the profile becomes linear, or the experiment duration may be insufficient to reach a maximum or steady state. Here, we present a software tool for Skin And Membrane Permeation data Analysis, SAMPA, that is easy to use and overcomes several of these difficulties. The SAMPA method and software have been validated on in vitro and in vivo permeation data on human, pig and rat skin and model stratum corneum lipid membranes using compounds that range from highly lipophilic polycyclic aromatic hydrocarbons to highly hydrophilic antiviral drug, with and without two permeation enhancers. The SAMPA performance was compared with the standard method using a linear part of the permeation profile and a complex mathematical model. SAMPA is a user-friendly, open-source software tool for analyzing the data obtained from skin and membrane permeation experiments. It runs on a Microsoft Windows platform and is freely available as a Supporting file to this article. Copyright © 2017 Elsevier Ltd. All rights reserved.

Novel serine-based gemini surfactants as chemical permeation enhancers of local anesthetics: A comprehensive study on structure-activity relationships, molecular dynamics and dermal delivery.

PubMed

Teixeira, Raquel S; Cova, Tânia F G G; Silva, Sérgio M C; Oliveira, Rita; do Vale, M Luísa C; Marques, Eduardo F; Pais, Alberto A C C; Veiga, Francisco J B

2015-06-01

This work aims at studying the efficacy of a series of novel biocompatible, serine-based surfactants as chemical permeation enhancers for two different local anesthetics, tetracaine and ropivacaine, combining an experimental and computational approach. The surfactants consist of gemini molecules structurally related, but with variations in headgroup charge (nonionic vs. cationic) and in the hydrocarbon chain lengths (main and spacer chains). In vitro permeation and molecular dynamics studies combined with cytotoxicity profiles were performed to investigate the permeation of both drugs, probe skin integrity, and rationalize the interactions at molecular level. Results show that these enhancers do not have significant deleterious effects on the skin structure and do not cause relevant changes on cell viability. Permeation across the skin is clearly improved using some of the selected serine-based gemini surfactants, namely the cationic ones with long alkyl chains and shorter spacer. This is noteworthy in the case of ropivacaine hydrochloride, which is not easily administered through the stratum corneum. Molecular dynamics results provide a mechanistic view of the surfactant action on lipid membranes that essentially corroborate the experimental observations. Overall, this study suggests the viability of these serine-based surfactants as suitable and promising delivery agents in pharmaceutical formulations. Copyright © 2015. Published by Elsevier B.V.

Development of skin structure and cutaneous water loss in nestling desert house sparrows from Saudi Arabia.

PubMed

Groff, Brandon; Muñoz-Garcia, Agustí; Yamaguchi, Mamoru; Williams, Joseph B

2007-06-01

The outer layer of the epidermis, the stratum corneum (SC), contains lipids and corneocytes, which together form layers that limit cutaneous water loss (CWL). We examined the development of structure of the SC and CWL in nestling House Sparrows (Passer domesticus) from Saudi Arabia. We measured CWL of nestlings, and characterized development of their epidermis using electron microscopy. We tested two antagonistic hypotheses, that CWL decreases as nestlings age, a response to increased thickness of SC, and an opposite idea that CWL increases as nestlings age even though the number of layers of the SC remains constant. CWL of nestling House Sparrows varied with developmental stages, in a non-linear fashion, but not significantly so. CWL of nestlings averaged 7.31+/-1.5 g H(2)O/(m(2) h), whereas for adults it was 4.95 g/(m(2) h); adult CWL was 67.7% that of nestlings. We found that morphology of the SC did not change linearly with age, but seemed to vary with developmental stage. CWL decreased as the SC thickness increased and as the total thickness of the corneocytes increased. Further, we found that CWL decreased as the thickness of the extracellular space increased, number of corneocytes increased, and proportion of the SC that is extracellular space increased.

Determination of Abutment Pressure in Coal Mines with Extremely Thick Alluvium Stratum: A Typical Kind of Rockburst Mines in China

NASA Astrophysics Data System (ADS)

Zhu, Sitao; Feng, Yu; Jiang, Fuxing

2016-05-01

This paper investigates the abutment pressure distribution in coal mines with extremely thick alluvium stratum (ETAS), which is a typical kind of mines encountering frequent intense rockbursts in China. This occurs due to poor understanding to abutment pressure distribution pattern and the consequent inappropriate mine design. In this study, a theoretical computational model of abutment pressure for ETAS longwall panels is proposed based on the analysis of load transfer mechanisms of key stratum (KS) and ETAS. The model was applied to determine the abutment pressure distribution of LW2302S in Xinjulong Coal Mine; the results of stress and microseismic monitoring verified the rationality of this model. The calculated abutment pressure of LW2302S was also used in the terminal mining line design of LW2301N for rockburst prevention, successfully protecting the main roadway from the adverse influence of the abutment pressure.

A 3D-psoriatic skin model for dermatological testing: The impact of culture conditions.

PubMed

Duque-Fernandez, Alexandra; Gauthier, Lydia; Simard, Mélissa; Jean, Jessica; Gendreau, Isabelle; Morin, Alexandre; Soucy, Jacques; Auger, Michèle; Pouliot, Roxane

2016-12-01

Inadequate representation of the human tissue environment during a preclinical screen can result in inaccurate predictions of compound effects. Consequently, pharmaceutical investigators are searching for preclinical models that closely resemble original tissue for predicting clinical outcomes. The current research aims to compare the impact of using serum-free medium instead of complete culture medium during the last step of psoriatic skin substitute reconstruction. Skin substitutes were produced according to the self-assembly approach. Serum-free conditions have no negative impact on the reconstruction of healthy or psoriatic skin substitutes presented in this study regarding their macroscopic or histological appearances. ATR-FTIR results showed no significant differences in the CH 2 bands between psoriatic substitutes cultured with or without serum, thus suggesting that serum deprivation did not have a negative impact on the lipid organization of their stratum corneum . Serum deprivation could even lead to a better organization of healthy skin substitute lipids. Percutaneous analyses demonstrated that psoriatic substitutes cultured in serum-free conditions showed a higher permeability to hydrocortisone compared to controls, while no significant differences in benzoic acid and caffeine penetration profiles were observed. Results obtained with this 3D-psoriatic skin substitute demonstrate the potential and versatility of the model. It could offer good prediction of drug related toxicities at preclinical stages performed in order to avoid unexpected and costly findings in the clinic. Together, these findings offer a new approach for one of the most important challenges of the 21st century, namely, prediction of drug toxicity.

LipidPedia: a comprehensive lipid knowledgebase.

PubMed

Kuo, Tien-Chueh; Tseng, Yufeng Jane

2018-04-10

Lipids are divided into fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, sterols, prenol lipids and polyketides. Fatty acyls and glycerolipids are commonly used as energy storage, whereas glycerophospholipids, sphingolipids, sterols and saccharolipids are common used as components of cell membranes. Lipids in fatty acyls, glycerophospholipids, sphingolipids and sterols classes play important roles in signaling. Although more than 36 million lipids can be identified or computationally generated, no single lipid database provides comprehensive information on lipids. Furthermore, the complex systematic or common names of lipids make the discovery of related information challenging. Here, we present LipidPedia, a comprehensive lipid knowledgebase. The content of this database is derived from integrating annotation data with full-text mining of 3,923 lipids and more than 400,000 annotations of associated diseases, pathways, functions, and locations that are essential for interpreting lipid functions and mechanisms from over 1,400,000 scientific publications. Each lipid in LipidPedia also has its own entry containing a text summary curated from the most frequently cited diseases, pathways, genes, locations, functions, lipids and experimental models in the biomedical literature. LipidPedia aims to provide an overall synopsis of lipids to summarize lipid annotations and provide a detailed listing of references for understanding complex lipid functions and mechanisms. LipidPedia is available at http://lipidpedia.cmdm.tw. yjtseng@csie.ntu.edu.tw. Supplementary data are available at Bioinformatics online.

Fractionated aliphatic alcohols as synthetic precursors of ultra long-chain monoacylglycerols for cosmetic applications.

PubMed

Pérez, B; Hansen, B S; Bulsara, P A; Rawlings, A V; Clarke, M J; Guo, Z

2017-10-01

Xerosis is an abnormally dry and flaky skin condition that is associated with a change in the packing behaviour of the lipid matrix in the stratum corneum (SC), the outermost layer of the skin. This skin condition can lead to an increase in transepidermal water loss (TEWL). As ultralong-chain fatty acids have a positive effect on maintaining the packing behaviour of the SC lipid matrix, a moisturizer which contains glycerides of ultralong-chain fatty acids could act as a semi-occlusive layer on the surface of the skin. This will lower the rate of water evaporation through the epidermis and consequently help prevent or improve skin xerosis. To identify a novel source of ultralong-chain lipids and develop monoacylglycerols with mixed fatty acyl chain lengths that have occlusive properties superior to petrolatum. Initially, Performacol 425, a mixture of very long-chain fatty alcohols, was fractionated using short path distillation to yield a fraction enriched with C22:0-C26:0 fatty alcohols. The fatty alcohol fraction was then oxidized using Jones reagent, and the resulting fatty acids were esterified with glycerol to yield the corresponding monoglycerides using Novozym 435. These were then evaluated using Fourier transform infrared spectroscopy, differential scanning calorimetry and water vapour transmission rate measurements. The monoacylglycerols enriched with C22:0-C26:0 displayed a melting point of 80°C and orthorhombic packing; packing behaviour mainly present in healthy SC. In addition, a phospholipid-structured emulsion containing 3% of the monoglycerides displayed occlusive properties superior to the vehicle containing 3% petrolatum jelly. Performacol 425 can be a potential source of fatty alcohols to synthesize monoacylglycerols that can improve the occlusive behaviour of phospholipid-structured emulsions. © 2017 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Rationalization of reduced penetration of drugs through ceramide gel phase membrane.

PubMed

Paloncýová, Markéta; DeVane, Russell H; Murch, Bruce P; Berka, Karel; Otyepka, Michal

2014-11-25

Since computing resources have advanced enough to allow routine molecular simulation studies of drug molecules interacting with biologically relevant membranes, a considerable amount of work has been carried out with fluid phospholipid systems. However, there is very little work in the literature on drug interactions with gel phase lipids. This poses a significant limitation for understanding permeation through the stratum corneum where the primary pathway is expected to be through a highly ordered lipid matrix. To address this point, we analyzed the interactions of p-aminobenzoic acid (PABA) and its ethyl (benzocaine) and butyl (butamben) esters with two membrane bilayers, which differ in their fluidity at ambient conditions. We considered a dioleoylphosphatidylcholine (DOPC) bilayer in a fluid state and a ceramide 2 (CER2, ceramide NS) bilayer in a gel phase. We carried out unbiased (100 ns long) and biased z-constraint molecular dynamics simulations and calculated the free energy profiles of all molecules along the bilayer normal. The free energy profiles converged significantly slower for the gel phase. While the compounds have comparable affinities for both membranes, they exhibit penetration barriers almost 3 times higher in the gel phase CER2 bilayer. This elevated barrier and slower diffusion in the CER2 bilayer, which are caused by the high ordering of CER2 lipid chains, explain the low permeability of the gel phase membranes. We also compared the free energy profiles from MD simulations with those obtained from COSMOmic. This method provided the same trends in behavior for the guest molecules in both bilayers; however, the penetration barriers calculated by COSMOmic did not differ between membranes. In conclusion, we show how membrane fluid properties affect the interaction of drug-like molecules with membranes.

Topically applied vitamin C and cysteine derivatives protect against UVA-induced photodegradation of suprofen in ex vivo pigskin.

PubMed

Moison, Ralf M W; Rijnkels, Jolanda M; Podda, Elena; Righele, Francesca; Tomasello, Federica; Caffieri, Sergio; Beijersbergen van Henegouwen, Gerard M J

2003-04-01

Exposure of the nonsteroidal anti-inflammatory drug suprofen (SUP) to UV-radiation results in the formation of radicals, reactive oxygen species (ROS), photodecarboxylated products and photoadducts with biomacromolecules. Using an ex vivo pigskin explant model, we investigated whether topical coapplication of the water-soluble antioxidants vitamin C (Lascorbic acid, ASC), N-acetyl-L-cysteine (NAC) or L-cysteine ethylester (CYSET) with SUP reduced ultraviolet A (UVA)-induced decomposition of SUP. UVA-induced changes in antioxidant bioavailability in the stratum corneum and epidermis were also studied. Epidermal bioavailability of SUP in sham-irradiated pigskin increased 2.2- to 4.1-fold after the lowest antioxidant doses (P < 0.05). As compared with no applied antioxidant, increasing doses of all tested antioxidants resulted in increased levels of SUP and decreased levels of photoproducts (P < 0.05). A maximal protection against SUP photodegradation of 70% was found after an ASC dose of 1 micromol/cm2; these values were 60% for a NAC dose of 10 micromol/cm2 and 50% for a CYSET dose of 5 micromol/cm2. Skin antioxidant levels increased with increasing applied dose (P < 0.05); the bioavailability of CYSET was approximately three-fold lower than that of ASC and NAC. UVA exposure resulted in 30-50% consumption of the topically applied ASC or NAC in the stratum corneum, whereas CYSET was not consumed. In conclusion, the topically applied water-soluble antioxidants ASC, NAC and CYSET protect against UVA-induced decomposition of SUP by scavenging radicals and ROS. Coapplication of these antioxidants may therefore be an effective way to reduce or prevent the phototoxic effects of SUP in vivo.

Moisture vapor transport channels for the improved attachment of a medical device to the human body.

PubMed

Cunningham, David D; Lowery, Michael G

2004-06-01

Attachment of a small, medical device to the human body for an extended period of time in an ambulatory setting requires the careful consideration of the physical form of the device and the physiological constraints limiting the time a device will stay on the skin. Factors such as the size of the device, the area of the device available for attachment to the skin, and the occlusive nature of the materials in the device are likely to affect adhesion. Here, plastic acrylic disks, 25 mm in diameter, containing a crisscross pattern of air-filled channels were tested on the forearm and abdomen using a moderately aggressive, unsupported, pressure-sensitive transfer adhesive in a pilot human clinical study. After vigorous exercise, droplets of moisture were observed in the channels followed by evaporation of the droplets over time. Disks without channels remained attached to the skin for about a day and a half, while disks containing 450 microm deep channels remained on the skin about three times longer. Little difference was found when the channel-to-channel spacing was increased from 1.3 to 1.6 mm, however 230 microm deep channels were less effective than 450 microm deep channels. Overall, the moisture vapor transport channels appear capable of reducing the moisture content of the outermost stratum corneum layer of the skin, increasing the strength of the stratum corneum, and increasing the time a device remains attached to the skin. The median trial-to-trial relative standard deviation of 45% observed in the pilot study can be used to design appropriately powered studies for the comparison of different device designs.

PBTK Modeling Demonstrates Contribution of Dermal and Inhalation Exposure Components to End-Exhaled Breath Concentrations of Naphthalene

PubMed Central

Kim, David; Andersen, Melvin E.; Chao, Yi-Chun E.; Egeghy, Peter P.; Rappaport, Stephen M.; Nylander-French, Leena A.

2007-01-01

Background Dermal and inhalation exposure to jet propulsion fuel 8 (JP-8) have been measured in a few occupational exposure studies. However, a quantitative understanding of the relationship between external exposures and end-exhaled air concentrations has not been described for occupational and environmental exposure scenarios. Objective Our goal was to construct a physiologically based toxicokinetic (PBTK) model that quantitatively describes the relative contribution of dermal and inhalation exposures to the end-exhaled air concentrations of naphthalene among U.S. Air Force personnel. Methods The PBTK model comprised five compartments representing the stratum corneum, viable epidermis, blood, fat, and other tissues. The parameters were optimized using exclusively human exposure and biological monitoring data. Results The optimized values of parameters for naphthalene were a) permeability coefficient for the stratum corneum 6.8 × 10−5 cm/hr, b) permeability coefficient for the viable epidermis 3.0 × 10−3 cm/hr, c) fat:blood partition coefficient 25.6, and d) other tissue:blood partition coefficient 5.2. The skin permeability coefficient was comparable to the values estimated from in vitro studies. Based on simulations of workers’ exposures to JP-8 during aircraft fuel-cell maintenance operations, the median relative contribution of dermal exposure to the end-exhaled breath concentration of naphthalene was 4% (10th percentile 1% and 90th percentile 11%). Conclusions PBTK modeling allowed contributions of the end-exhaled air concentration of naphthalene to be partitioned between dermal and inhalation routes of exposure. Further study of inter- and intraindividual variations in exposure assessment is required to better characterize the toxicokinetic behavior of JP-8 components after occupational and/or environmental exposures. PMID:17589597

PBTK modeling demonstrates contribution of dermal and inhalation exposure components to end-exhaled breath concentrations of naphthalene.

PubMed

Kim, David; Andersen, Melvin E; Chao, Yi-Chun E; Egeghy, Peter P; Rappaport, Stephen M; Nylander-French, Leena A

2007-06-01

Dermal and inhalation exposure to jet propulsion fuel 8 (JP-8) have been measured in a few occupational exposure studies. However, a quantitative understanding of the relationship between external exposures and end-exhaled air concentrations has not been described for occupational and environmental exposure scenarios. Our goal was to construct a physiologically based toxicokinetic (PBTK) model that quantitatively describes the relative contribution of dermal and inhalation exposures to the end-exhaled air concentrations of naphthalene among U.S. Air Force personnel. The PBTK model comprised five compartments representing the stratum corneum, viable epidermis, blood, fat, and other tissues. The parameters were optimized using exclusively human exposure and biological monitoring data. The optimized values of parameters for naphthalene were a) permeability coefficient for the stratum corneum 6.8 x 10(-5) cm/hr, b) permeability coefficient for the viable epidermis 3.0 x 10(-3) cm/hr, c) fat:blood partition coefficient 25.6, and d) other tissue:blood partition coefficient 5.2. The skin permeability coefficient was comparable to the values estimated from in vitro studies. Based on simulations of workers' exposures to JP-8 during aircraft fuel-cell maintenance operations, the median relative contribution of dermal exposure to the end-exhaled breath concentration of naphthalene was 4% (10th percentile 1% and 90th percentile 11%). PBTK modeling allowed contributions of the end-exhaled air concentration of naphthalene to be partitioned between dermal and inhalation routes of exposure. Further study of inter- and intraindividual variations in exposure assessment is required to better characterize the toxicokinetic behavior of JP-8 components after occupational and/or environmental exposures.

Preparation and evaluation of microemulsion-based transdermal delivery of total flavone of rhizoma arisaematis

PubMed Central

Shen, Li-Na; Zhang, Yong-Tai; Wang, Qin; Xu, Ling; Feng, Nian-Ping

2014-01-01

The aims of the present study were to investigate the skin permeation and cellular uptake of a microemulsion (ME) containing total flavone of rhizoma arisaematis (TFRA), and to evaluate its effects on skin structure. Pseudo-ternary phase diagrams were constructed to evaluate ME regions with various surfactants and cosurfactants. Eight formulations of oil-in-water MEs were selected as vehicles, and in vitro skin-permeation experiments were performed to optimize the ME formulation and to evaluate its permeability, in comparison to that of an aqueous suspension. Laser scanning confocal microscopy and fluorescent-activated cell sorting were used to explore the cellular uptake of rhodamine 110-labeled ME in human epidermal keratinocytes (HaCaT) and human embryonic skin fibroblasts (CCC-ESF-1). The structure of stratum corneum treated with ME was observed using a scanning electron microscope. Furthermore, skin irritation was tested to evaluate the safety of ME. ME formulated with 4% ethyl oleate (weight/weight), 18% Cremophor EL® (weight/weight), and 18% Transcutol® P, with 1% Azone to enhance permeation, showed good skin permeability. ME-associated transdermal fluxes of schaftoside and isoschaftoside, two major effective constituents of TFRA, were 3.72-fold and 5.92-fold higher, respectively, than those achieved using aqueous suspensions. In contrast, in vitro studies revealed that uptake by HaCaT and CCC-ESF-1 cells was lower with ME than with an aqueous suspension. Stratum corneum loosening and shedding was observed in nude mouse skin treated with ME, although ME produced no observable skin irritation in rabbits. These findings indicated that ME enhanced transdermal TFRA delivery effectively and showed good biocompatibility with skin tissue. PMID:25092976

New effective azelaic acid liposomal gel formulation of enhanced pharmaceutical bioavailability.

PubMed

Burchacka, E; Potaczek, P; Paduszyński, P; Karłowicz-Bodalska, K; Han, T; Han, S

2016-10-01

Azelaic acid is a naturally occurring saturated C9-dicarboxylic acid which has been shown to be effective in the treatment of comedonal acne and inflammatory acne, as well as hiperpigmentary skin disorders. The aim of the present study is to compare new developed liposomal hydrogel (lipogel) and commercially available product in terms of the active substance-azelaic acid bioavailability. Topical formulations were evaluated for physical parameters, such as pH measurement, organoleptic evaluation and liposome size analysis in lipogel formulation. In addition, studies were performed on in vitro antimicrobial preservation, stability and accumulation in the stratum corneum according to guidelines established by European Pharmacopoeia and International Conferences on Harmonisation. The new formula for liposomal gel with azelaic acid has the stability required for pharmaceutical preparations. Moreover, presented formulation F2 reveals a very high accumulation (187.5μg/cm 2 ) of an active substance in the stratum corneum, which results in opportunity to decrease of the API content to 10% in comparison to a reference formula: commercially available cream with 20% of azelaic acid. The study reveals that the final formula of lipogel F2 with azelaic acid had acceptable physical parameters that showed that they were compatible with the skin and in addition this formulation passed stability studies. In vitro antimicrobial preservation studies showed that the formulated lipogel F2 showed strong antibacterial activity; thus, no preservatives were added to the final composition of the preparation. The present study concludes that the formulated lipogel F2 with azelaic acid is stable, efficient in antimicrobial preservation and reveals improved active substance bioavailability. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Moisturizing effect of cosmetic formulations containing Aloe vera extract in different concentrations assessed by skin bioengineering techniques.

PubMed

Dal'Belo, Susi Elaine; Gaspar, Lorena Rigo; Maia Campos, Patrícia Maria Berardo Gonçalves

2006-11-01

The polysaccharide-rich composition of Aloe vera extracts (Aloe barbadensis Miller), often used in cosmetic formulations, may impart moisturizing properties to the product. The aim of this study was to evaluate the effect of cosmetic formulations containing different concentrations of freeze-dried Aloe vera extract on skin hydration, after a single and a 1- and 2-week period of application, by using skin bioengineering techniques. Stable formulations containing 5% (w/w) of a trilaureth-4 phosphate-based blend were supplemented with 0.10%, 0.25% or 0.50% (w/w) of freeze-dried Aloe vera extract and applied to the volar forearm of 20 female subjects. Skin conditions in terms of the water content of the stratum corneum and of transepidermal water loss (TEWL) (Corneometer CM 825 and Tewameter TM 210) were analysed before and after a single and 1- and 2-week period of daily application. After a single application, only formulations supplemented with 0.25% and 0.50% (w/w) of Aloe vera extract increased the water content of the stratum corneum, while after the 2-week period application, all formulations containing the extract (0.10%, 0.25% and 0.50%) had the same effect, in both cases as compared with the vehicle. TEWL was not modified after a single and after 1- and 2-week period of application, when compared with the vehicle. Our results show that freeze-dried Aloe vera extract is a natural effective ingredient for improving skin hydration, possibly through a humectant mechanism. Consequently, it may be used in moisturizing cosmetic formulations and also as a complement in the treatment of dry skin.

Update of Ablative Fractionated Lasers to Enhance Cutaneous Topical Drug Delivery.

PubMed

Waibel, Jill S; Rudnick, Ashley; Shagalov, Deborah R; Nicolazzo, Danielle M

2017-08-01

Ablative fractional lasers (AFXL) enhance uptake of therapeutics and this newly emerging field is called laser-assisted drug delivery (LAD). This new science has emerged over the past decade and is finding its way into clinical practice. LAD is poised to change how medicine delivers drugs. Topical and systemic application of pharmaceutical agents for therapeutic effect is an integral part of medicine. With topical therapy, the stratum corneum barrier of the skin impairs the ability of drugs to enter the body. The purpose of LAD is to alter the stratum corneum, epidermis, and dermis to facilitate increased penetration of a drug, device, or cell to its respected target. AFXL represents an innovative, non-invasive strategy to overcome the epidermal barrier. LAD employs three steps: (1) breakdown of the skin barrier with a laser, (2) optional use a laser for a therapeutic effect, (3) delivery of the medicine through laser channels to further enhance the therapeutic effect. The advantages of using lasers for drug delivery include the ease of accessibility, the non-invasive aspect, and its effectiveness. By changing the laser settings, one may use LAD to have a drug remain locally within the skin or to have systemic delivery. Many drugs are not intended for use in the dermis and so it has yet to be determined which drugs are appropriate for this technique. It appears this developing technology has the ability to be a new delivery system for both localized and systemic delivery of drugs, cells, and other molecules. With responsible development AFXL-assisted drug delivery may become a new important part of medicine.

Dry skin conditions are related to the recovery rate of skin temperature after cold stress rather than to blood flow.

PubMed

Yoshida-Amano, Yasuko; Nomura, Tomoko; Sugiyama, Yoshinori; Iwata, Kayoko; Higaki, Yuko; Tanahashi, Masanori

2017-02-01

Cutaneous blood flow plays an important role in the thermoregulation, oxygen supply, and nutritional support necessary to maintain the skin. However, there is little evidence for a link between blood flow and skin physiology. Therefore, we conducted surveys of healthy volunteers to determine the relationship(s) between dry skin properties and cutaneous vascular function. Water content of the stratum corneum, transepidermal water loss, and visual dryness score were investigated as dry skin parameters. Cutaneous blood flow in the resting state, the recovery rate (RR) of skin temperature on the hand after a cold-stress test, and the responsiveness of facial skin blood flow to local cooling were examined as indices of cutaneous vascular functions. The relationships between dry skin parameters and cutaneous vascular functions were assessed. The RR correlated negatively with the visual dryness score of skin on the leg but correlated positively with water content of the stratum corneum on the arm. No significant correlation between the resting state of blood flow and dry skin parameters was observed. In both the face and the body, deterioration in skin dryness from summer to winter was significant in subjects with low RR. The RR correlated well with the responsiveness of facial skin blood flow to local cooling, indicating that the RR affects systemic dry skin conditions. These results suggest that the RR but not blood flow at the resting state is associated with dry skin conditions and is involved in skin homeostasis during seasonal environmental changes. © 2016 The Authors. International Journal of Dermatology published by John Wiley & Sons Ltd on behalf of International Society of Dermatology.

Improvement of skin conditions by ingestion of Aspergillus kawachii (Koji) extract containing 14-dehydroergosterol in a randomized, double-blind, controlled trial

PubMed Central

Sugihara, Yoshihiko; Ikushima, Shigehito; Miyake, Mika; Kirisako, Takayoshi; Yada, Yukihiro; Fujiwara, Daisuke

2018-01-01

Purpose The present study examined the effect of ingestion of Koji extract containing 14-dehydroergosterol (14-DHE), prepared from Aspergillus kawachii NBRC4308, on improvement of skin conditions among healthy volunteers. Subjects and methods In a randomized, double-blind, placebo-controlled, parallel-group study, 70 healthy adult women who felt that their skin was dry ingested either a placebo dietary supplement or Koji extract (200 mg/day) supplement containing 0.1% 14-DHE for 12 weeks. Throughout the treatment period and for 4 weeks afterward, objective indicators – including moisture content of the stratum corneum, trans-epidermal water loss (TEWL), and skin wrinkles – were evaluated; in addition, the subjects answered a questionnaire on their skin conditions with ratings on a visual analog scale. Statistical analysis was conducted on the basis of differences from baseline scores. Results Compared with the placebo group, the Koji extract group showed significantly increased forearm moisture at 4, 8, and 16 weeks (p < 0.05 on unpaired t-test). The questionnaire survey showed a marked improvement in skin conditions, particularly crow’s feet, in the Koji extract group versus the placebo group at 8 weeks (p < 0.05 by unpaired t-test). Furthermore, the Koji extract group showed a trend (p < 0.10) toward improvement in skin moisture (at 4 weeks), dryness around the eyes/mouth (at 4 weeks), and overall skin condition (at 8 weeks) versus the placebo group. Conclusion Ingestion of Koji extract containing 14-DHE was demonstrated to have positive effects toward improving skin conditions – in particular, on increasing skin moisture in the stratum corneum. PMID:29563825

The influence of a non-occlusive bi-layer composite membrane on skin barrier properties. A non-invasive evaluation with a right-left intra-individual pre/post comparison study.

PubMed

Brazzelli, V; Berardesca, E; Rona, C; Borroni, G

2008-01-01

The purpose of this placebo-controlled right-left intra-individual pre/post comparison study was to evaluate the efficacy of a new bi-layer composite membrane, composed of a layer of knitted cotton and a layer of semi-permeable polyurethane, developed in order to improve skin hydration. Eighteen healthy subjects entered the study. A T-shirt, dedicated to this study, was prepared and it was worn for 8 h, mimicking overnight wearing. Before and at the removal of the T-shirt an objective quantification of skin parameters was performed by measuring hydration, transepidermal water loss (TEWL) and skin surface pH, bilaterally, on the inner side of the forearm. Measurements were performed both at the interface between the skin and the bi-layer composite membrane or cotton and on the outer side of the membrane (to assess permeation of water and occlusive properties of the product) with and without a single application of a moisturizer. A statistically significant improvement of skin hydration, recorded on the stratum corneum underneath the bi-layer membrane versus cotton alone, was measured both with (p < 0.0001) and without application of the moisturizer (p < 0.002). TEWL was shown to decrease significantly on the side of the bi-layer membrane, if compared with cotton (p < 0.008), after application of the moisturizer. TEWL through the membrane showed no significant differences as compared to placebo, confirming the permeability of the fabric. Our data suggest that this bi-layer composite membrane can promote the hydration process of the stratum corneum, increasing the hydrating properties of the moisturizer agent. (c) 2007 S. Karger AG, Basel

Structural Changes in the Skin of Hairless Mice Following Exposure to Sulfur Mustard Correlate with Inflammation and DNA Damage

PubMed Central

Joseph, Laurie B.; Gerecke, Donald R.; Heck, Diane E.; Black, Adrienne T.; Sinko, Patrick J.; Cervelli, Jessica A.; Casillas, Robert P.; Babin, Michael C.; Laskin, Debra L.; Laskin, Jeffrey D.

2011-01-01

Sulfur mustard (SM, bis(2-chloroethyl)sulfide) is a bifunctional alkylating agent that causes dermal inflammation, edema and blistering. To investigate the pathogenesis of SM-induced injury, we used a vapor cup model which provides an occlusive environment in which SM is in constant contact with the skin. The dorsal skin of SKH-1 hairless mice was exposed to saturated SM vapor or air control. Histopathological changes, inflammatory markers and DNA damage were analyzed 1–14 days later. After 1 day, SM caused epidermal thinning, stratum corneum shedding, basal cell karyolysis, hemorrhage and macrophage and neutrophil accumulation in the dermis. Cleaved caspase-3 and phosphorylated histone 2A.X (phospho-H2A.X), markers of apoptosis and DNA damage, respectively, were increased whereas proliferating cell nuclear antigen (PCNA) was down-regulated after SM exposure. By 3 days, epithelial cell hypertrophy, edema, parakeratosis and loss of epidermal structures were noted. Enzymes generating pro-inflammatory mediators including myeloperoxidase and cyclooxygenase-2 were upregulated. After 7 days, keratin-10, a differentiation marker, was evident in the stratum corneum. This was associated with an underlying eschar, as neoepidermis began to migrate at the wound edges. Trichrome staining revealed increased collagen deposition in the dermis. PCNA expression in the epidermis was correlated with hyperplasia, hyperkeratosis, and parakeratosis. By 14 days, there was epidermal regeneration with extensive hyperplasia, and reduced expression of cleaved caspase-3, cyclooxygenase-2 and phospho-H2A.X. These findings are consistent with the pathophysiology of SM-induced skin injury in humans suggesting that the hairless mouse can be used to investigate the dermatoxicity of vesicants and the potential efficacy of countermeasures. PMID:21672537

Melanin fate in the human epidermis: a reassessment of how best to detect and analyse histologically.

PubMed

Joly-Tonetti, Nicolas; Wibawa, Judata I D; Bell, Mike; Tobin, Desmond

2016-07-01

Melanin is the predominant pigment responsible for skin colour and is synthesized by the melanocyte in the basal layer of the epidermis and then transferred to surrounding keratinocytes. Despite its optical properties, melanin is barely detectable in unstained sections of human epidermis. However, identification and localization of melanin is of importance for the study of skin pigmentation in health and disease. Current methods for the histologic quantification of melanin are suboptimal and are associated with significant risk of misinterpretation. The aim of this study was to reassess the existing literature and to develop a more effective histological method of melanin quantification in human skin. Moreover, we confirm that Warthin-Starry (WS) stain provides a much more sensitive and more specific melanin detection method than the commonplace Fontana-Masson (FM) stain. For example, WS staining sensitivity allowed the visualization of melanin even in very pale Caucasian skin that was missed by FM or Von Kossa (VK) stains. From our reassessment of the histology-related literature, we conclude that so-called melanin dust is most likely an artifact of discoloration due to non-specific silver deposition in the stratum corneum. Unlike FM and VK, WS was not associated with this non-specific stratum corneum darkening, misinterpreted previously as 'degraded' melanin. Finally, WS melanin particle counts were largely similar to previously reported manual counts by transmission electron microscopy, in contrast to both FM and VK. Together these findings allow us to propose a new histology/Image J-informed method for the accurate and precise quantification of epidermal melanin in skin. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fourier transform Raman spectroscopic studies of human and animal skins

NASA Astrophysics Data System (ADS)

Barry, Brian W.; Edwards, Howell G.; Williams, Adrian C.

1994-01-01

The stratum corneum is the outermost layer of the skin and provides the principal barrier for the ingress of chemicals and environmental toxins into human and animal tissues. However, human skin has several advantages for the administration of therapeutic agents (transdermal drug delivery), but problems occur with the supply, storage, and biohazardous nature of human tissue. Hence, alternative animal tissues have been prepared to model drug diffusion across human skin but the molecular basis for comparison is lacking. Here, FT-Raman spectra of mammalian (human and pig) and reptilian (snake) skins have been obtained and the structural dissimilarities are correlated with drug diffusion studies across the tissues.

The pH of the main Brazilian commercial moisturizers and liquid soaps: considerations on the repair of the skin barrier*

PubMed Central

Gonçalves, Giovana M; Brianezi, Gabrielli; Miot, Hélio Amante

2017-01-01

The pH of the skin is slightly acidic (4.6 to 5.8) which is important for appropriate antibacterial, antifungal, constitution of barrier function, as well as structuring and maturation of the stratum corneum. This study aimed to evaluate the pH of the main commercial moisturizers and liquid soaps in Brazil. Thus, pH of the products was quantified by pH meter in three measurements. A total of 38 moisturizers and six commercial liquid soaps were evaluated. Mean pH of 63% and 50% of the moisturizing and liquid soaps presented results above 5.5, disfavoring repair, function, and synthesis of dermal barrier. PMID:29166523

The pH of the main Brazilian commercial moisturizers and liquid soaps: considerations on the repair of the skin barrier.

PubMed

Gonçalves, Giovana M; Brianezi, Gabrielli; Miot, Hélio Amante

2017-01-01

The pH of the skin is slightly acidic (4.6 to 5.8) which is important for appropriate antibacterial, antifungal, constitution of barrier function, as well as structuring and maturation of the stratum corneum. This study aimed to evaluate the pH of the main commercial moisturizers and liquid soaps in Brazil. Thus, pH of the products was quantified by pH meter in three measurements. A total of 38 moisturizers and six commercial liquid soaps were evaluated. Mean pH of 63% and 50% of the moisturizing and liquid soaps presented results above 5.5, disfavoring repair, function, and synthesis of dermal barrier.

Evaluation and Management of Refractory Acne Vulgaris in Adolescent and Adult Men.

PubMed

McCarty, Morgan

2016-04-01

Acne vulgaris alters the normal skin physiology, impairing stratum corneum and transepidermal water loss. A male's normal skin physiologic state is different than a female's and may have implications when choosing treatment when the skin is altered in a disease state. Transepidermal water loss, pH, and sebum production are different between the sexes. Several underlying conditions present in male acne patients at several ages that may require a more in-depth evaluation. As knowledge of the pathogenesis of acne expands, the differences in skin physiology between the sexes may alter the manner in which male patients with acne medications are approached. Copyright © 2016 Elsevier Inc. All rights reserved.

Novel TGM5 mutations in acral peeling skin syndrome.

PubMed

van der Velden, Jaap J A J; van Geel, Michel; Nellen, Ruud G L; Jonkman, Marcel F; McGrath, John A; Nanda, Arti; Sprecher, Eli; van Steensel, Maurice A M; McLean, W H Irwin; Cassidy, Andrew J

2015-04-01

Acral peeling skin syndrome (APSS, MIM #609796) is a rare autosomal recessive disorder characterized by superficial exfoliation and blistering of the volar and dorsal aspects of hands and feet. The level of separation is at the junction of the stratum granulosum and stratum corneum. APSS is caused by mutations in the TGM5 gene encoding transglutaminase-5, which is important for structural integrity of the outermost epidermal layers. The majority of patients originate from Europe and carry a p.(Gly113Cys) mutation in TGM5. In this study, we report both European and non-European families carrying other mutations in the TGM5 gene. In 5 patients, we found 3 novel mutations: c.1001+2_1001+3del, c.1171G>A and c.1498C>T. To confirm their pathogenicity, we performed functional analyses with a transglutaminase activity assay, determined alternative splicing by reverse-transcribed PCR analysis and used databases and in silico prediction tools. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Age-related differences in morphological characteristics of residual skin surface components collected from the surface of facial skin of healthy male volunteers.

PubMed

Chalyk, N E; Bandaletova, T Y; Kyle, N H; Petyaev, I M

2017-05-01

Global increase of human longevity results in the emergence of previously ignored ageing-related problems. Skin ageing is a well-known phenomenon, but active search for scientific approaches to its prevention and even skin rejuvenation is a relatively new area. Although the structure and composition of the stratum corneum (SC), the superficial layer of epidermis, is well studied, relatively little is known about the residual skin surface components (RSSC) that overlay the surface of the SC. The aim of this study was to examine morphological features of RSSC samples non-invasively collected from the surface of human facial skin for the presence of age-related changes. Residual skin surface component samples were collected by swabbing from the surface of facial skin of 60 adult male volunteers allocated in two age groups: 34 subjects aged in the range 18-32 years and 26 subjects aged in the range 58-72 years. The collected samples were analysed microscopically: the size of the lipid droplets was measured; desquamated corneocytes and lipid crystals were counted; and microbial presence was assessed semi-quantitatively. Age-related changes were revealed for all studied components of the RSSC. There was a significant (P = 0.0126) decrease in the size of lipid droplets among older men. Likewise, significantly (P = 0.0252) lower numbers of lipid crystals were present in this group. In contrast, microbial presence in the RSSC was significantly (P = 0.0019) increased in the older group. There was also a trend towards more abundant corneocyte desquamation among older men, but the difference has not reached statistical significance (P = 0.0636). Non-invasively collected RSSC samples present an informative material for studying age-related changes on the surface of the SC of human facial skin. The results of this study confirm earlier observations regarding age-associated decline of the efficiency of the epidermal barrier and can be used for testing new approaches to skin

Altered synaptic marker abundance in the hippocampal stratum oriens of Ts65Dn mice is associated with exuberant expression of versican

PubMed Central

Howell, Matthew D; Gottschall, Paul E

2012-01-01

DS (Down syndrome), resulting from trisomy of chromosome 21, is the most common cause of genetic mental retardation; however, the molecular mechanisms underlying the cognitive deficits are poorly understood. Growing data indicate that changes in abundance or type of CSPGs (chondroitin sulfate proteoglycans) in the ECM (extracellular matrix) can influence synaptic structure and plasticity. The purpose of this study was to identify changes in synaptic structure in the hippocampus in a model of DS, the Ts65Dn mouse, and to determine the relationship to proteoglycan abundance and/or cleavage and cognitive disability. We measured synaptic proteins by ELISA and changes in lectican expression and processing in the hippocampus of young and old Ts65Dn mice and LMCs (littermate controls). In young (5 months old) Ts65Dn hippocampal extracts, we found a significant increase in the postsynaptic protein PSD-95 (postsynaptic density 95) compared with LMCs. In aged (20 months old) Ts65Dn hippocampus, this increase was localized to hippocampal stratum oriens extracts compared with LMCs. Aged Ts65Dn mice exhibited impaired hippocampal-dependent spatial learning and memory in the RAWM (radial-arm water maze) and a marked increase in levels of the lectican versican V2 in stratum oriens that correlated with the number of errors made in the final RAWM block. Ts65Dn stratum oriens PNNs (perineuronal nets), an extension of the ECM enveloping mostly inhibitory interneurons, were dispersed over a larger area compared with LMC mice. Taken together, these data suggest a possible association with alterations in the ECM and inhibitory neurotransmission in the Ts65Dn hippocampus which could contribute to cognitive deficits. PMID:22225533

Mathematical models to describe iontophoretic transport in vitro and in vivo and the effect of current application on the skin barrier.

PubMed

Gratieri, Taís; Kalia, Yogeshvar N

2013-02-01

The architecture and composition of the stratum corneum make it a particularly effective barrier against the topical and transdermal delivery of hydrophilic molecules and ions. As a result, different strategies have been explored in order to expand the range of therapeutic agents that can be administered by this route. Iontophoresis involves the application of a small electric potential to increase transport into and across the skin. Since current flow is preferentially via transport pathways with at least some aqueous character, it is ideal for hydrosoluble molecules containing ionisable groups. Hence, the physicochemical properties that limit partitioning and passive diffusion through the intercellular lipid matrix are beneficial for electrically-assisted delivery. The presence of fixed ionisable groups in the skin (pI 4-4.5) means that application of the electric field results in a convective solvent flow (i.e., electroosmosis) in the direction of ion motion so as to neutralise membrane charge. Hence, under physiological conditions, cation electrotransport is due to both electromigration and electroosmosis-their relative contribution depends on the formulation conditions and the physicochemical properties of the permeant. Different mathematical models have been developed to provide a theoretical framework in order to explain iontophoretic transport kinetics. They usually involve solutions of the Nernst-Planck equation - using either the constant field (Goldman) or electroneutrality (Nernst) approximations - with or without terms for the convective solvent flow component. Investigations have also attempted to elucidate the nature of ion transport pathways and to explain the effect of current application on the electrical properties of the skin-more specifically, the stratum corneum. These studies have led to the development of different equivalent circuit models. These range from simple parallel arrangements of a resistor and a capacitor to the inclusion of the

Cross stratum resources protection in fog-computing-based radio over fiber networks for 5G services

NASA Astrophysics Data System (ADS)

Guo, Shaoyong; Shao, Sujie; Wang, Yao; Yang, Hui

2017-09-01

In order to meet the requirement of internet of things (IoT) and 5G, the cloud radio access network is a paradigm which converges all base stations computational resources into a cloud baseband unit (BBU) pool, while the distributed radio frequency signals are collected by remote radio head (RRH). A precondition for centralized processing in the BBU pool is an interconnection fronthaul network with high capacity and low delay. However, it has become more complex and frequent in the interaction between RRH and BBU and resource scheduling among BBUs in cloud. Cloud radio over fiber network has been proposed in our previous work already. In order to overcome the complexity and latency, in this paper, we first present a novel cross stratum resources protection (CSRP) architecture in fog-computing-based radio over fiber networks (F-RoFN) for 5G services. Additionally, a cross stratum protection (CSP) scheme considering the network survivability is introduced in the proposed architecture. The CSRP with CSP scheme can effectively pull the remote processing resource locally to implement the cooperative radio resource management, enhance the responsiveness and resilience to the dynamic end-to-end 5G service demands, and globally optimize optical network, wireless and fog resources. The feasibility and efficiency of the proposed architecture with CSP scheme are verified on our software defined networking testbed in terms of service latency, transmission success rate, resource occupation rate and blocking probability.

Lipid14: The Amber Lipid Force Field

PubMed Central

2015-01-01

The AMBER lipid force field has been updated to create Lipid14, allowing tensionless simulation of a number of lipid types with the AMBER MD package. The modular nature of this force field allows numerous combinations of head and tail groups to create different lipid types, enabling the easy insertion of new lipid species. The Lennard-Jones and torsion parameters of both the head and tail groups have been revised and updated partial charges calculated. The force field has been validated by simulating bilayers of six different lipid types for a total of 0.5 μs each without applying a surface tension; with favorable comparison to experiment for properties such as area per lipid, volume per lipid, bilayer thickness, NMR order parameters, scattering data, and lipid lateral diffusion. As the derivation of this force field is consistent with the AMBER development philosophy, Lipid14 is compatible with the AMBER protein, nucleic acid, carbohydrate, and small molecule force fields. PMID:24803855

The effects of polar excipients transcutol and dexpanthenol on molecular mobility, permeability, and electrical impedance of the skin barrier.

PubMed

Björklund, Sebastian; Pham, Quoc Dat; Jensen, Louise Bastholm; Knudsen, Nina Østergaard; Nielsen, Lars Dencker; Ekelund, Katarina; Ruzgas, Tautgirdas; Engblom, Johan; Sparr, Emma

2016-10-01

In the development of transdermal and topical products it is important to understand how formulation ingredients interact with the molecular components of the upper layer of the skin, the stratum corneum (SC), and thereby influence its macroscopic barrier properties. The aim here was to investigate the effect of two commonly used excipients, transcutol and dexpanthenol, on the molecular as well as the macroscopic properties of the skin membrane. Polarization transfer solid-state NMR methods were combined with steady-state flux and impedance spectroscopy measurements to investigate how these common excipients influence the molecular components of SC and its barrier function at strictly controlled hydration conditions in vitro with excised porcine skin. The NMR results provide completely new molecular insight into how transcutol and dexpanthenol affect specific molecular segments of both SC lipids and proteins. The presence of transcutol or dexpanthenol in the formulation at fixed water activity results in increased effective skin permeability of the model drug metronidazole. Finally, impedance spectroscopy data show clear changes of the effective skin capacitance after treatment with transcutol or dexpanthenol. Based on the complementary data, we are able to draw direct links between effects on the molecular properties and on the macroscopic barrier function of the skin barrier under treatment with formulations containing transcutol or dexpanthenol. Copyright © 2016 Elsevier Inc. All rights reserved.

Ceramide 1 and ceramide 3 act synergistically on skin hydration and the transepidermal water loss of sodium lauryl sulfate-irritated skin.

PubMed

Huang, Huey-Chun; Chang, Tsong-Min

2008-08-01

Stratum corneum intercellular lipids, such as ceramides, play an important role in the regulation of skin water barrier homeostasis and water-holding capacity. Aim To evaluate the potential water retention capacity of control emulsion and three oil-in-water (o/w) emulsions containing ceramide 1, ceramide 3, or both. Fifteen healthy Asian women (age, 20-30 years) with healthy skin, pretreated with sodium lauryl sulfate (SLS), applied the tested emulsions twice daily over a period of 28 days. Skin hydration and transepidermal water loss (TEWL) values were measured on the indicated days with a Corneometer(R)825 and a TEWAMETER TM210, respectively. The maximum increase in skin humidity was reached after 4 weeks, with values of 21.9 +/- 1.8% and 8.9 +/- 0.9% for emulsion C and control emulsion, respectively. The maximum decrease in TEWL was also reached after 4 weeks, with values of 36.7 +/- 4.7% and 5.1 +/- 0.8% for the same emulsions. It can be concluded that all the tested ceramide-containing emulsions improved skin barrier function when compared with untreated skin. There was some indication that ceramides 1 and 3 contained in emulsion C might exert a beneficial synergistic effect on skin biochemical properties, such as skin hydration and TEWL, and play a key role in the protection mechanism against SLS irritation.

Enantioselective penetration enhancing effect of carvone on the in vitro transdermal permeation of nicorandil.

PubMed

Krishnaiah, Yellela S R; Nada, Aly

2012-01-01

The objective was to investigate the difference in penetration enhancing effect of R-carvone, S-carvone and RS-carvone on the in vitro transdermal drug permeation. In vitro permeation studies were carried out across neonatal rat epidermis from 2%w/v HPMC (hydroxypropyl methylcellulose) gel containing 4%w/v of nicorandil (a model drug) and a selected concentration (12%w/v) of either R-carvone, S-carvone or RS-carvone against a control. The stratum corneum (SC) of rats was treated with vehicle (70%v/v ethanol-water) or ethanolic solutions of 12%w/v R-carvone, S-carvone or RS-carvone. The enhancement ratio (ER) of R-carvone, S-carvone and RS-carvone when compared to control was about 37.1, 31.2 and 29.9, respectively indicating enantioselective penetration enhancing effect of carvone enantiomers. Furthermore, there was a significant decrease in the lag time required to produce a steady-state flux of nicorandil with S-carvone when compared to R-carvone and RS-carvone. DSC and FT-IR studies indicate that the investigated enantiomers of carvone exhibit a difference in their ability to affect the cellular organization of SC lipids and proteins thereby showing enantioselective transdermal drug permeation. It was concluded that R-carvone exhibited a higher penetration enhancing activity on transdermal permeation of nicorandil when compared to its S-isomer or racemic mixture.

Epidermal Overexpression of Xenobiotic Receptor PXR Impairs the Epidermal Barrier and Triggers Th2 Immune Response.

PubMed

Elentner, Andreas; Schmuth, Matthias; Yannoutsos, Nikolaos; Eichmann, Thomas O; Gruber, Robert; Radner, Franz P W; Hermann, Martin; Del Frari, Barbara; Dubrac, Sandrine

2018-01-01

The skin is in daily contact with environmental pollutants, but the long-term effects of such exposure remain underinvestigated. Many of these toxins bind and activate the pregnane X receptor (PXR), a ligand-activated transcription factor that regulates genes central to xenobiotic metabolism. The objective of this work was to investigate the effect of constitutive activation of PXR in the basal layer of the skin to mimic repeated skin exposure to noxious molecules. We designed a transgenic mouse model that overexpresses the human PXR gene linked to the herpes simplex VP16 domain under the control of the keratin 14 promoter. We show that transgenic mice display increased transepidermal water loss and elevated skin pH, abnormal stratum corneum lipids, focal epidermal hyperplasia, activated keratinocytes expressing more thymic stromal lymphopoietin, a T helper type 2/T helper type 17 skin immune response, and increased serum IgE. Furthermore, the cutaneous barrier dysfunction precedes development of the T helper type 2/T helper type 17 inflammation in transgenic mice, thereby mirroring the time course of atopic dermatitis development in humans. Moreover, further experiments suggest increased PXR signaling in the skin of patients with atopic dermatitis when compared with healthy skin. Thus, PXR activation by environmental pollutants may compromise epidermal barrier function and favor an immune response resembling atopic dermatitis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Sebum and Hydration Levels in Specific Regions of Human Face Significantly Predict the Nature and Diversity of Facial Skin Microbiome.

PubMed

Mukherjee, Souvik; Mitra, Rupak; Maitra, Arindam; Gupta, Satyaranjan; Kumaran, Srikala; Chakrabortty, Amit; Majumder, Partha P

2016-10-27

The skin microbiome varies across individuals. The causes of these variations are inadequately understood. We tested the hypothesis that inter-individual variation in facial skin microbiome can be significantly explained by variation in sebum and hydration levels in specific facial regions of humans. We measured sebum and hydration from forehead and cheek regions of healthy female volunteers (n = 30). Metagenomic DNA from skin swabs were sequenced for V3-V5 regions of 16S rRNA gene. Altogether, 34 phyla were identified; predominantly Actinobacteria (66.3%), Firmicutes (17.7%), Proteobacteria (13.1%) and Bacteroidetes (1.4%). About 1000 genera were identified; predominantly Propionibacterium (58.6%), Staphylococcus (8.6%), Streptococcus (4.0%), Corynebacterium (3.6%) and Paracoccus (3.3%). A subset (n = 24) of individuals were sampled two months later. Stepwise multiple regression analysis showed that cheek sebum level was the most significant predictor of microbiome composition and diversity followed by forehead hydration level; forehead sebum and cheek hydration levels were not. With increase in cheek sebum, the prevalence of Actinobacteria (p = 0.001)/Propionibacterium (p = 0.002) increased, whereas microbiome diversity decreased (Shannon Index, p = 0.032); this was opposite for other phyla/genera. These trends were reversed for forehead hydration levels. Therefore, the nature and diversity of facial skin microbiome is jointly determined by site-specific lipid and water levels in the stratum corneum.

Pilosebaceous targeting by isotretenoin-loaded invasomal gel for the treatment of eosinophilic pustular folliculitis: optimization, efficacy and cellular analysis.

PubMed

Dwivedi, Mohit; Sharma, Vijay; Pathak, Kamla

2017-02-01

Eosinophilic pustular folliculitis is a secondary symptom associated with HIV infection appears as levels of CD4 lymphocyte cells and T4 lymphocyte cell. Isotretinoin, an analog of vitamin A (retinoid) alters the DNA transcription mechanism and interferes in the process of DNA formation. It also inhibits the eosinophilic chemotactic factors present in sebaceous lipids and in the stratum corneum of patients suffering from this ailment. The present research was aimed to formulate isotretenoin-loaded invasomal gel to deliver and target the drug to pilosebaceous follicular unit. Nine invasomal formulations (F1-F9) were prepared applying 3 2 factorial designs and characterized. Formulation F9 was selected as optimized formulation due to optimum results and highest %CDP of 85.94 ± 1.86% in 8 h. Transmission electron microscopy (TEM) suggested uniformity in vesicles shape and size in F9 and developed as invasomal gel (IG). Clinical phase-I, phase-II, and phase-III studies will be required before using on human patients. Confocal laser scanning microscopy (CLSM) validates that IG successfully reaches the pilosebaceous follicular unit and further studied on cell line (SZ-95) exhibited IC50 of ≤8 (25 μM of isotretenoin). Cell cycle analysis confirmed IG arrested the cell growth up to 82% with insignificant difference to pure isotretenion.

Permeation-Enhancing Effects and Mechanisms of Borneol and Menthol on Ligustrazine: A Multiscale Study using In Vitro and Coarse-Grained Molecular Dynamics Simulation Methods.

PubMed

Dai, Xingxing; Wang, Ran; Wu, Zhimin; Guo, Shujuan; Yang, Chang; Ma, Lina; Chen, Liping; Shi, Xinyuan; Qiao, Yanjiang

2018-06-20

Borneol (BO) and menthol (MEN) are two widely used natural permeation enhancers in the transdermal drug delivery system. In previous studies, their permeation enhancement effects and mechanisms of action on the hydrophobic drug osthole (logP=3.8) and hydrophilic drug 5-fluorouracil (logP=-0.9) have been studied. In this study, ligustrazine (LTZ), whose logP is 1.3, was used as a model drug to provide a comprehensive understanding of the influence of its logP on the permeation-enhancing effects of BO and MEN. Both BO and MEN enhanced the permeation of LTZ through the skin stratum corneum, as determined using the modified Franz diffusion cell experiment. The enhancement mechanisms were illustrated by coarse-grained molecular dynamics simulations as follows: at low concentrations, the enhancing ratio of MEN was higher than that of BO because of the stronger perturbation effects of MEN on the lipid bilayer, making it looser and facilitating LTZ diffusion. However, at high concentrations, in addition to the diffusion mechanism, BO induced the formation of water channels to improve the permeation of LTZ; however, MEN had no significant effects through this mechanism. Their results were different from those found with osthole and 5-fluorouracil and have been discussed in this paper. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Potential Applications of Phyto-Derived Ceramides in Improving Epidermal Barrier Function.

PubMed

Tessema, Efrem N; Gebre-Mariam, Tsige; Neubert, Reinhard H H; Wohlrab, Johannes

2017-01-01

The outer most layer of the skin, the stratum corneum, consists of corneocytes which are coated by a cornified envelope and embedded in a lipid matrix of ordered lamellar structure. It is responsible for the skin barrier function. Ceramides (CERs) are the backbone of the intercellular lipid membranes. Skin diseases such as atopic dermatitis and psoriasis and aged skin are characterized by dysfunctional skin barrier and dryness which are associated with reduced levels of CERs. Previously, the effectiveness of supplementation of synthetic and animal-based CERs in replenishing the depleted natural skin CERs and restoring the skin barrier function have been investigated. Recently, however, the barrier function improving effect of plant-derived CERs has attracted much attention. Phyto-derived CERs (phytoCERs) are preferable due to their assumed higher safety as they are mostly isolated from dietary sources. The beneficial effects of phytoCER-based oral dietary supplements for skin hydration and skin barrier reinforcement have been indicated in several studies involving animal models as well as human subjects. Ingestible dietary supplements containing phytoCERs are also widely available on the market. Nonetheless, little effort has been made to investigate the potential cosmetic applications of topically administered phytoCERs. Therefore, summarizing the foregoing investigations and identifying the gap in the scientific data on plant-derived CERs intended for skin-health benefits are of paramount importance. In this review, an attempt is made to synthesize the information available in the literature regarding the effects of phytoCER-based oral dietary supplements on skin hydration and barrier function with the underlying mechanisms. © 2017 S. Karger AG, Basel.

An ex vivo human skin model for studying skin barrier repair.

PubMed

Danso, Mogbekeloluwa O; Berkers, Tineke; Mieremet, Arnout; Hausil, Farzia; Bouwstra, Joke A

2015-01-01

In the studies described in this study, we introduce a novel ex vivo human skin barrier repair model. To develop this, we removed the upper layer of the skin, the stratum corneum (SC) by a reproducible cyanoacrylate stripping technique. After stripping the explants, they were cultured in vitro to allow the regeneration of the SC. We selected two culture temperatures 32 °C and 37 °C and a period of either 4 or 8 days. After 8 days of culture, the explant generated SC at a similar thickness compared to native human SC. At 37 °C, the early and late epidermal differentiation programmes were executed comparably to native human skin with the exception of the barrier protein involucrin. At 32 °C, early differentiation was delayed, but the terminal differentiation proteins were expressed as in stripped explants cultured at 37 °C. Regarding the barrier properties, the SC lateral lipid organization was mainly hexagonal in the regenerated SC, whereas the lipids in native human SC adopt a more dense orthorhombic organization. In addition, the ceramide levels were higher in the cultured explants at 32 °C and 37 °C than in native human SC. In conclusion, we selected the stripped ex vivo skin model cultured at 37 °C as a candidate model to study skin barrier repair because epidermal and SC characteristics mimic more closely the native human skin than the ex vivo skin model cultured at 32 °C. Potentially, this model can be used for testing formulations for skin barrier repair. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The SwissLipids knowledgebase for lipid biology

PubMed Central

Liechti, Robin; Hyka-Nouspikel, Nevila; Niknejad, Anne; Gleizes, Anne; Götz, Lou; Kuznetsov, Dmitry; David, Fabrice P.A.; van der Goot, F. Gisou; Riezman, Howard; Bougueleret, Lydie; Xenarios, Ioannis; Bridge, Alan

2015-01-01

Motivation: Lipids are a large and diverse group of biological molecules with roles in membrane formation, energy storage and signaling. Cellular lipidomes may contain tens of thousands of structures, a staggering degree of complexity whose significance is not yet fully understood. High-throughput mass spectrometry-based platforms provide a means to study this complexity, but the interpretation of lipidomic data and its integration with prior knowledge of lipid biology suffers from a lack of appropriate tools to manage the data and extract knowledge from it. Results: To facilitate the description and exploration of lipidomic data and its integration with prior biological knowledge, we have developed a knowledge resource for lipids and their biology—SwissLipids. SwissLipids provides curated knowledge of lipid structures and metabolism which is used to generate an in silico library of feasible lipid structures. These are arranged in a hierarchical classification that links mass spectrometry analytical outputs to all possible lipid structures, metabolic reactions and enzymes. SwissLipids provides a reference namespace for lipidomic data publication, data exploration and hypothesis generation. The current version of SwissLipids includes over 244 000 known and theoretically possible lipid structures, over 800 proteins, and curated links to published knowledge from over 620 peer-reviewed publications. We are continually updating the SwissLipids hierarchy with new lipid categories and new expert curated knowledge. Availability: SwissLipids is freely available at http://www.swisslipids.org/. Contact: alan.bridge@isb-sib.ch Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25943471