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Sample records for facilitate skin penetration

  1. Facilitated skin penetration of lidocaine: combination of a short-term iontophoresis and microemulsion formulation.

    Science.gov (United States)

    Sintov, Amnon C; Brandys-Sitton, Roy

    2006-06-19

    The objective of this study was to demonstrate the potential of the application of a short-term iontophoresis on the topical delivery of lidocaine hydrochloride from a microemulsion-based system. Five- and 10-min durations of anodal iontophoresis applied onto porcine skin were examined in combination with a microemulsion containing 2.5% lidocaine hydrochloride. A similar combination (10-min iontophoresis with microemulsion in the anodal electrode) was also examined in vivo in a rat model. It was shown in vitro that by combining microemulsion application with a 10-min iontophoresis of 1.13 mA/cm2 electric current density, a significantly increased flux was obtained compared with a combination of aqueous drug solution with the same iontophoresis protocol. In vivo studies revealed that 57.71 +/- 18.65 and 18.43 +/- 9.17 microg cm(-2) were reached in the epidermis and dermis, respectively, at t = 30 min of microemulsion application, when iontophoresis was applied for 10 min. In contrast, the application of aqueous solution-iontophoresis resulted in a relatively lower drug accumulation (21.44 +/- 10.42 and 5.30 +/- 2.25 microg cm(-2) in the epidermis and dermis, respectively, at t = 30) with more rapid clearance of the drug from the skin. Ten-minute application of a low-current electric field on a new topical microemulsion appears to make significant changes in skin permeability. The potential advantages of this procedure include significantly increased flux, accumulation of a large skin drug depot, short lag times, reduced irritation (compared to long-term iontophoresis), simplicity and ease of compliance.

  2. Penetration through the Skin Barrier

    DEFF Research Database (Denmark)

    Nielsen, Jesper Bo; Benfeldt, Eva; Holmgaard, Rikke

    2016-01-01

    . During recent decades, the latter has received increased attention as a route for intentionally delivering drugs to patients. This has stimulated research in methods for sampling, measuring and predicting percutaneous penetration. Previous chapters have described how different endogenous, genetic...... and exogenous factors may affect barrier characteristics. The present chapter introduces the theory for barrier penetration (Fick's law), and describes and discusses different methods for measuring the kinetics of percutaneous penetration of chemicals, including in vitro methods (static and flow......-through diffusion cells) as well as in vivo methods (microdialysis and microperfusion). Then follows a discussion with examples of how different characteristics of the skin (age, site and integrity) and of the penetrants (size, solubility, ionization, logPow and vehicles) affect the kinetics of percutaneous...

  3. Enhanced chlorhexidine skin penetration with eucalyptus oil

    Directory of Open Access Journals (Sweden)

    Worthington Tony

    2010-09-01

    Full Text Available Abstract Background Chlorhexidine digluconate (CHG is a widely used skin antiseptic, however it poorly penetrates the skin, limiting its efficacy against microorganisms residing beneath the surface layers of skin. The aim of the current study was to improve the delivery of chlorhexidine digluconate (CHG when used as a skin antiseptic. Method Chlorhexidine was applied to the surface of donor skin and its penetration and retention under different conditions was evaluated. Skin penetration studies were performed on full-thickness donor human skin using a Franz diffusion cell system. Skin was exposed to 2% (w/v CHG in various concentrations of eucalyptus oil (EO and 70% (v/v isopropyl alcohol (IPA. The concentration of CHG (μg/mg of skin was determined to a skin depth of 1500 μm by high performance liquid chromatography (HPLC. Results The 2% (w/v CHG penetration into the lower layers of skin was significantly enhanced in the presence of EO. Ten percent (v/v EO in combination with 2% (w/v CHG in 70% (v/v IPA significantly increased the amount of CHG which penetrated into the skin within 2 min. Conclusion The delivery of CHG into the epidermis and dermis can be enhanced by combination with EO, which in turn may improve biocide contact with additional microorganisms present in the skin, thereby enhancing antisepsis.

  4. Percutaneous penetration through slightly damaged skin

    DEFF Research Database (Denmark)

    Nielsen, Jesper B

    2005-01-01

    Guidelines for experimental studies of percutaneous penetration prescribe optimal barrier integrity of the skin. The barrier integrity of the skin exposed in occupational or household situations is, however, not always ideal, and skin problems are among the most dominant reasons for absence from...... work. We have therefore evaluated an experimental model for percutaneous penetration through slightly damaged skin. The influence of a slight damage to the skin was evaluated using five pesticides covering a wide range of solubilities. We used an experimental model with static diffusion cells mounted...... with human skin. A slight damage to the barrier integrity was induced by pre-treatment of the skin with sodium lauryl sulphate (SLS) before pesticide exposure. The experimental model with 3 h pre-treatment with SLS (0.1% or 0.3%) assured a significant but controlled damage to the barrier integrity, a damage...

  5. Pseudo skin factor due to partial penetration

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, A.C.; Chen, J.C.; Raghavan, R.

    1983-10-01

    In this study the authors examine the pseudo skin factor due to partial penetration in a two-layer reservoir when only one layer is open to flow. They show that the pseudo skin factor can be correlated as a unique function of three reservoir parameters and in some cases can be accurately correlated as a function of two reservoir parameters. They also present graphs and procedures for estimating the pseudo skin factor.

  6. Pseudo skin factor due to partial penetration

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, A.C.; Chen, J.C.; Raghavan, R.

    1983-01-01

    This study examines the pseudo skin factor due to partial penetration in a 2-layer reservoir when only one layer is open to flow. The pseudo skin factor can be correlated as a unique function of 3 reservoir parameters and in some cases can be correlated accurately as a function of 2 reservoir parameters. Graphs and procedures for estimating the pseudo skin factor are presented. 17 references.

  7. An overview of skin penetration enhancers: penetration enhancing activity, skin irritation potential and mechanism of action

    Directory of Open Access Journals (Sweden)

    Sarunyoo Songkro

    2009-08-01

    Full Text Available Transdermal drug delivery has attracted considerable attention over the past 2-3 decades in regard of its many potentialadvantages. However, the role of the skin as a protective barrier renders skin absorption of most drugs problematic. Therefore,skin penetration enhancers are frequently used in the field of transdermal drug delivery in order to reversibly reduce thebarrier function of the stratum corneum, the outermost layer of the skin. To date, a wide range of chemical compounds havebeen shown to enhance the skin penetration of therapeutic drugs. This review presents a critical account of the most commonlyused chemical penetration enhancers (fatty acids and surfactants, and some newer classes of chemical enhancers (terpenes,polymers, monoolein, oxazolidinones, with emphasis on their efficacy, mechanism of action, and skin irritation potential. Thisreview also discusses the traditional and more recently developed methods for the screening and evaluation of chemical penetration enhancers, and addresses the continuing problems in the rational selection of a chemical penetration enhancer for a specific drug to be delivered via the transdermal route.

  8. Is skin penetration a determining factor in skin sensitization ...

    Science.gov (United States)

    Summary:Background. It is widely accepted that substances that cannot penetrate through the skin will not be sensitisers. Thresholds based on relevant physicochemical parameters such as a LogKow > 1 and a MW 1 is a true requirement for sensitisation.Methods. A large dataset of substances that had been evaluated for their skin sensitisation potential, together with measured LogKow values was compiled from the REACH database. The incidence of skin sensitisers relative to non-skin sensitisers below and above the LogKow = 1 threshold was evaluated. Results. 1482 substances with associated skin sensitisation outcomes and measured LogKow values were identified. 305 substances had a measured LogKow skin sensitisation above and below the LogKow = 1 threshold. Reaction chemistry considerations could explain the skin sensitisation observed for the 38 sensitisers with a LogKow skin sensitisation potential and potency. Using the REACH data extracted to test out the validity of common assumptions in the skin sensitization AOP. Builds on trying to develop a proof of concept IATA

  9. Investigation of the Efficacy of Transdermal Penetration Enhancers Through the Use of Human Skin and a Skin Mimic Artificial Membrane.

    Science.gov (United States)

    Balázs, Boglárka; Vizserálek, Gábor; Berkó, Szilvia; Budai-Szűcs, Mária; Kelemen, András; Sinkó, Bálint; Takács-Novák, Krisztina; Szabó-Révész, Piroska; Csányi, Erzsébet

    2016-03-01

    The aim of this study was to investigate the behavior of promising penetration enhancers through the use of 2 different skin test systems. Hydrogel-based transdermal formulations were developed with ibuprofen as a nonsteroidal anti-inflammatory drug. Transcutol and sucrose esters were used as biocompatible penetration enhancers. The permeability measurements were performed with ex vivo Franz diffusion cell methods and a newly developed Skin Parallel Artificial Membrane Permeability Assays (PAMPA) model. Franz diffusion measurement is commonly used as a research tool in studies of diffusion through synthetic membranes in vitro or penetration through ex vivo human skin, whereas Skin PAMPA involves recently published artificial membrane-based technology for the fast prediction of skin penetration. It is a 96-well plate-based model with optimized artificial membrane structure containing free fatty acid, cholesterol, and synthetic ceramide analog compounds to mimic the stratum corneum barrier function. Transdermal preparations containing 2.64% of different sucrose esters and/or Transcutol and a constant (5%) of ibuprofen were investigated to determine the effects of these penetration enhancers. The study demonstrated the good correlation of the permeability data obtained through use of human skin membrane and the in vitro Skin PAMPA system. The Skin PAMPA artificial membrane serves as quick and relatively deep tool in the early stages of transdermal delivery systems, through which the enhancing efficacy of excipients can be screened so as to facilitate the choice of effective penetration components.

  10. The isolated perfused human skin flap model: A missing link in skin penetration studies?

    OpenAIRE

    Ternullo, Selenia; de Weerd, Louis; Flaten, Gøril Eide; Holsæter, Ann Mari; Skalko-Basnet, Natasa

    2016-01-01

    Development of effective (trans)dermal drug delivery systems requires reliable skinmodels to evaluate skin drug penetration. The isolated perfused human skin flap remainsmetabolically active tissue for up to 6 h during in vitro perfusion. We introduce the isolated perfused human skin flap as a close-to-in vivo skin penetration model. To validate the model's ability to evaluate skin drug penetration the solutions of a hydrophilic (calcein) and a lipophilic (rhodamine) fluorescence ...

  11. Liposome surface charge influence on skin penetration behaviour.

    Science.gov (United States)

    Gillet, A; Compère, P; Lecomte, F; Hubert, P; Ducat, E; Evrard, B; Piel, G

    2011-06-15

    Vesicular systems have shown their ability to increase dermal and transdermal drug delivery. Their mechanism of drug transport into and through the skin has been investigated but remains a much debated question. Several researchers have outlined that drug penetration can be influenced by modifying the surface charge of liposomes. In the present work we study the influence of particle surface charge on skin penetration. The final purpose is the development of a carrier system which is able to enhance the skin delivery of two model drugs, betamethasone and betamethasone dipropionate. Liposomes were characterised by their size, morphology, zeta potential, encapsulation efficiency and stability. Ex vivo diffusion studies using Franz diffusion cells were performed. Confocal microscopy was performed to visualise the penetration of fluorescently labelled liposomes into the skin. This study showed the potential of negatively charged liposomes to enhance the skin penetration of betamethasone and betamethasone dipropionate.

  12. Penetration of ASM 981 in canine skin: a comparative study.

    Science.gov (United States)

    Gutzwiller, Meret E Ricklin; Reist, Martin; Persohn, Elke; Peel, John E; Roosje, Petra J

    2006-01-01

    ASM 981 has been developed for topical treatment of inflammatory skin diseases. It specifically inhibits the production and release of pro-inflammatory cytokines. We measured the skin penetration of ASM 981 in canine skin and compared penetration in living and frozen skin. To make penetration of ASM 981 visible in dog skin, tritium labelled ASM 981 was applied to a living dog and to defrosted skin of the same dog. Using qualitative autoradiography the radioactive molecules were detected in the lumen of the hair follicles until the infundibulum, around the superficial parts of the hair follicles and into a depth of the dermis of 200 to 500 microm. Activity could not be found in deeper parts of the hair follicles, the dermis or in the sebaceous glands. Penetration of ASM 981 is low in canine skin and is only equally spread in the upper third of the dermis 24 hours after application. Penetration in frozen skin takes even longer than in living canine skin but shows the same distribution.

  13. The isolated perfused human skin flap model: A missing link in skin penetration studies?

    Science.gov (United States)

    Ternullo, Selenia; de Weerd, Louis; Flaten, Gøril Eide; Holsæter, Ann Mari; Škalko-Basnet, Nataša

    2017-01-01

    Development of effective (trans)dermal drug delivery systems requires reliable skin models to evaluate skin drug penetration. The isolated perfused human skin flap remains metabolically active tissue for up to 6h during in vitro perfusion. We introduce the isolated perfused human skin flap as a close-to-in vivo skin penetration model. To validate the model's ability to evaluate skin drug penetration the solutions of a hydrophilic (calcein) and a lipophilic (rhodamine) fluorescence marker were applied. The skin flaps were perfused with modified Krebs-Henseleit buffer (pH7.4). Infrared technology was used to monitor perfusion and to select a well-perfused skin area for administration of the markers. Flap perfusion and physiological parameters were maintained constant during the 6h experiments and the amount of markers in the perfusate was determined. Calcein was detected in the perfusate, whereas rhodamine was not detectable. Confocal images of skin cross-sections shoved that calcein was uniformly distributed through the skin, whereas rhodamine accumulated in the stratum corneum. For comparison, the penetration of both markers was evaluated on ex vivo human skin, pig skin and cellophane membrane. The proposed perfused flap model enabled us to distinguish between the penetrations of the two markers and could be a promising close-to-in vivo tool in skin penetration studies and optimization of formulations destined for skin administration.

  14. Evaluation of nicotinamide microemulsion on the skin penetration enhancement.

    Science.gov (United States)

    Boonme, Prapaporn; Boonthongchuay, Chalida; Wongpoowarak, Wibul; Amnuaikit, Thanaporn

    2016-01-01

    This study purposed to evaluate a microemulsion containing nicotinamide for its characteristics, stability, and skin penetration and retention comparing with a solution of nicotinamide in 2:1 mixture of water and isopropyl alcohol (IPA). The microemulsion system was composed of 1:1 mixture of Span80 and Tween80 as a surfactant mixture, isopropyl palmitate (IPP) as an oil phase, and 2:1 mixture of water and IPA as an aqueous phase. Nicotinamide microemulsion was prepared by dissolving the active in the aqueous phase before simply mixing with the other components. It was determined for its characteristics and stability under various conditions. The skin penetration and retention studies of nicotinamide microemulsion and solution were performed by modified Franz diffusion cells, using newborn pig skin as the membrane. The results showed that nicotinamide microemulsion could be obtained as clear yellowish liquid, was water-in-oil (w/o) type, possessed Newtonian flow, and exhibited physicochemical stability when kept at 4 °C and room temperature (≈30 ± 2 °C) during 3 months. From the skin penetration data, the microemulsion could enhance the skin penetration of nicotinamide comparing with the solution. Additionally, nicotinamide microemulsion could provide much higher amount of skin retention than that of skin penetration, resulting in suitability for a cosmeceutical product.

  15. Setup for investigating gold nanoparticle penetration through reconstructed skin and comparison to published human skin data

    Science.gov (United States)

    Labouta, Hagar I.; Thude, Sibylle; Schneider, Marc

    2013-06-01

    Owing to the limited source of human skin (HS) and the ethical restrictions of using animals in experiments, in vitro skin equivalents are a possible alternative for conducting particle penetration experiments. The conditions for conducting penetration experiments with model particles, 15-nm gold nanoparticles (AuNP), through nonsealed skin equivalents are described for the first time. These conditions include experimental setup, sterility conditions, effective applied dose determination, skin sectioning, and skin integrity check. Penetration at different exposure times (two and 24 h) and after tissue fixation (fixed versus unfixed skin) are examined to establish a benchmark in comparison to HS in an attempt to get similar results to HS experiments presented earlier. Multiphoton microscopy is used to detect gold luminescence in skin sections. λex=800 nm is used for excitation of AuNP and skin samples, allowing us to determine a relative index for particle penetration. Despite the observed overpredictability of penetration into skin equivalents, they could serve as a first fast screen for testing the behavior of nanoparticles and extrapolate their penetration behavior into HS. Further investigations are required to test a wide range of particles of different physicochemical properties to validate the skin equivalent-human skin particle penetration relationship.

  16. LeciPlex, invasomes, and liposomes: A skin penetration study.

    Science.gov (United States)

    Shah, Sanket M; Ashtikar, Mukul; Jain, Ankitkumar S; Makhija, Dinesh T; Nikam, Yuvraj; Gude, Rajiv P; Steiniger, Frank; Jagtap, Aarti A; Nagarsenker, Mangal S; Fahr, Alfred

    2015-07-25

    The present study compares three vesicular systems, cationic LeciPlex, invasomes, and conventional liposomes for their ability to deliver drugs deep into the skin. Skin penetration ability of the three vesicular systems was studied for two drugs namely idebenone (antioxidant/anticancer) and azelaic acid (antiacne). All systems showed sizes in nanometer range with small polydispersity indices. Vesicular systems were characterized by CryoTEM studies to understand the differences in morphology of the vesicular systems. Ex vivo human skin penetration studies suggested a pattern in penetration of drugs in different layers of the skin: LeciPlex showed higher penetration for idebenone whereas invasomes showed higher penetration of azelaic acid. Ex vivo study using a fluorescent dye (DiI) was performed to understand the differences in the penetration behavior of the three vesicular systems on excised human skin. In vitro cytotoxicity studies on B16F10 melanoma cell lines revealed, when loaded with idebenone, LeciPlex formulations had the superior activity followed by invasomes and liposomes. In vitro antimicrobial study of azelaic acid loaded systems on Propionibacterium acne revealed high antimicrobial activity for DDAB leciplex followed by almost equal activity for invasomes and CTAB LeciPlex followed by liposomes. Whereas antiacne efficacy study in rats for azelaic acid loaded systems, invasomes exhibited the best antiacne efficacy followed by liposomes and LeciPlex.

  17. Skin penetration enhancement by a microneedle device (Dermaroller) in vitro

    DEFF Research Database (Denmark)

    Badran, M M; Kuntsche, Judith; Fahr, A

    2009-01-01

    This study focused on the in vitro evaluation of skin perforation using a new microneedle device (Dermaroller) with different needle lengths (150, 500 and 1500 microm). The influence of the microneedle treatment on the morphology of the skin surface (studied by light and scanning electron...... compared with an aqueous solution. Elevated TEWL values were measured after Dermaroller treatment compared to untreated human skin with a gradual increase of the TEWL over the first hour whereas afterwards the TEWL values decreased probably caused by a reduction of the pore size with time. Skin perforation...... microscopy), on the transepidermal water loss (TEWL) and on the penetration and permeation of hydrophilic model drugs was investigated using excised human full-thickness skin. Furthermore, invasomes - highly flexible phospholipid vesicles containing terpenes and ethanol as penetration enhancer - were...

  18. Optical methods for measurements of skin penetration.

    Science.gov (United States)

    Gotter, B; Faubel, W; Neubert, R H H

    2008-01-01

    Fourier transform infrared photoacoustic (PAS), photothermal deflection (PDS) and Raman spectroscopy belong to the modern innovative noninvasive analytical tools that are beginning to be recognized as highly potential techniques for the noninvasive study of biological tissues and human skin under in vivo conditions. They can be applied to obtain information regarding the molecular composition of the skin down to several hundred micrometers below the skin surface. All three methods allow depth-resolved investigations. While PAS and PDS use a frequency modulation of the excitation beam to reach deeper regions in the sample, the principle of confocal Raman microspectroscopy (CRM) is a movement of the specimen in the focal plane. In consideration of depth measurements PAS and PDS complete the applicable spectrum of CRM, since Raman microscopy requires particular transparent materials.

  19. Near infrared laser penetration and absorption in human skin

    Science.gov (United States)

    Nasouri, Babak; Murphy, Thomas E.; Berberoglu, Halil

    2014-02-01

    For understanding the mechanisms of low level laser/light therapy (LLLT), accurate knowledge of light interaction with tissue is necessary. In this paper, we present a three dimensional, multi-layer Monte Carlo simulation tool for studying light penetration and absorption in human skin. The skin is modeled as a three-layer participating medium, namely epidermis, dermis, and subcutaneous, where its geometrical and optical properties are obtained from the literature. Both refraction and reflection are taken into account at the boundaries according to Snell's law and Fresnel relations. A forward Monte Carlo method was implemented and validated for accurately simulating light penetration and absorption in absorbing and anisotropically scattering media. Local profiles of light penetration and volumetric absorption densities were simulated for uniform as well as Gaussian profile beams with different spreads at 155 mW average power over the spectral range from 1000 nm to 1900 nm. The results show the effects of beam profiles and wavelength on the local fluence within each skin layer. Particularly, the results identify different wavelength bands for targeted deposition of power in different skin layers. Finally, we show that light penetration scales well with the transport optical thickness of skin. We expect that this tool along with the results presented will aid researchers resolve issues related to dose and targeted delivery of energy in tissues for LLLT.

  20. Contribution to the penetration of radionuclides across the skin

    Energy Technology Data Exchange (ETDEWEB)

    Koprda, V.; Harangozo, M.; Kassai, Z. [Faculty of Chemical Technology, Slovak University of Technology, Radlinskeho, Bratislava (Slovakia)

    2000-05-01

    The human skin as well as the skin of animal species represent a strong barrier against the permeation of ionic forms of substances into an organism. Radionuclides of cesium, cobalt and actinides belong to frequent potential contaminants of human body at an accidental radioactive contamination. Regarding the actual composition of contaminating mixture of radionuclides the damage of an organism after internal contamination is proportional to the extent of penetrated amounts of radionuclides across the skin. In this paper: the time dependence of permeation of {sup 137}Cs{sup +}, {sup 60}Co{sup 2+}, and {sup 147}Pm{sup 3+} from aqueous solution through animal skin model was studied, the biologic structure mostly responsible for the barrier effect was selected and proved, the relative importance of the main diffusion pathways for {sup 137}Cs{sup +}, {sup 60}Co{sup 2+} and {sup 147}Pm{sup 3+}, the diffusion across the intact skin and the diffusion through the hair channels was assessed, the effect of isotopic carrier on the pentration process was studied, and the retarding capacities of different substances were researched. In all experiments the radioactive tracers were used. The experimental arrangement consisted of Franz-type vertical permeation cells. The well standardized animal skin models were chosen: fresh skin from abdominal region of 5 day old rats (5DR) of Wistar strain (Breeding Farm Dobra Voda, SK) and 9 day old rats (9DR), resp.. The skins of 5DR are still hairless, and 9DR are just short haired. The 5DR skin was used intact, and also with decreasing thickness of horny layer after it had been stripped with Scotch type (3M) 5-20 times respectively, or the skin had been splitted in 60degC hot water, whereby the whole epidermis was removed. Ions penetrated in vitro through the skin from donor solution (vehicle water) to receptor solution (phosphate buffered saline), were determined in aliquots sampled in 1,3,5,7 a 24 hours. The penetrated amounts of ions were

  1. Diverse host-seeking behaviors of skin-penetrating nematodes.

    Directory of Open Access Journals (Sweden)

    Michelle L Castelletto

    2014-08-01

    Full Text Available Skin-penetrating parasitic nematodes infect approximately one billion people worldwide and are responsible for some of the most common neglected tropical diseases. The infective larvae of skin-penetrating nematodes are thought to search for hosts using sensory cues, yet their host-seeking behavior is poorly understood. We conducted an in-depth analysis of host seeking in the skin-penetrating human parasite Strongyloides stercoralis, and compared its behavior to that of other parasitic nematodes. We found that Str. stercoralis is highly mobile relative to other parasitic nematodes and uses a cruising strategy for finding hosts. Str. stercoralis shows robust attraction to a diverse array of human skin and sweat odorants, most of which are known mosquito attractants. Olfactory preferences of Str. stercoralis vary across life stages, suggesting a mechanism by which host seeking is limited to infective larvae. A comparison of odor-driven behavior in Str. stercoralis and six other nematode species revealed that parasite olfactory preferences reflect host specificity rather than phylogeny, suggesting an important role for olfaction in host selection. Our results may enable the development of new strategies for combating harmful nematode infections.

  2. THE PENETRATION OF VESICANT VAPORS INTO HUMAN SKIN.

    Science.gov (United States)

    Nagy, S M; Golumbic, C; Stein, W H; Fruton, J S; Bergmann, M

    1946-07-20

    Analytical methods which are accurate to about 1 per cent have been developed for the determination of small amounts (ca. 500 gamma) of bis(beta-chloroethyl)-sulfide (H), ethyl-bis(beta-chloroethyl)amine (EBA), tris(beta-chloroethyl)amine (TBA), beta-chloroethyl-benzylsulfide (benzyl-H), and beta-chloroethyl-ethylsulfide (ethyl-H). The determinations are made by micro titration of the HCl liberated upon complete hydrolysis of the vesicants. A description is given of an apparatus suitable for applying vapors of vesicants to unit areas of skin. A very precise and reproducible micropipetting technique is described for the introduction of the vesicants into the penetration apparatus. By means of this penetration apparatus studies have been made of several factors which may influence the rate at which vesicant vapors penetrate into skin. Model experiments have been performed in which H was allowed to vaporize and the vapor was absorbed on a surface such as that of diethylene glycol or vaseline. It has been found that if the surface of liquid H is increased by spreading the agent on filter paper, the rate of evaporation is markedly increased. Furthermore, if the vapor is agitated by means of a magnetically driven fan, the rate of absorption by diethylene glycol is greatly accelerated. With vaseline as the absorbing surface it has been found that the area of the absorbing surface has an effect on the rate of absorption of H vapor. More H is absorbed by vaseline spread on filter paper to give a rough surface than is absorbed by a smooth film of vaseline. Measurements of the rate of penetration into human skin of H, EBA, TBA, benzyl-H, and ethyl-H vapors have been performed at 21-23 degrees C. and 30-31 degrees C. by means of the penetration apparatus described in this paper. The measurements were carred out on human volunteers under conditions of controlled temperature and humidity. When human skin is exposed to air saturated with H vapor, the H penetrates the skin of the

  3. Skin absorption of actinides: influence of solvents or chelates on skin penetration ex vivo.

    Science.gov (United States)

    Tazrart, Anissa; Bolzinger, Marie-Alexandrine; Coudert, Sylvie; Lamart, Stephanie; Miller, Brian W; Angulo, Jaime F; Briançon, Stéphanie; Griffiths, Nina M

    2017-06-01

    To evaluate skin penetration and retention of americium (Am) and plutonium (Pu), in different chemical forms relevant to the nuclear industry and to treatment by chelation. Percutaneous penetration of different Am and Pu forms were evaluated using viable pig skin with the Franz cell diffusion system. The behavior of the complex Pu-tributyl phosphate (Pu-TBP), Am or Pu complexed to the chelator Diethylene triamine pentaacetic acid (DTPA) and the effect of dimethyl sulfoxide (DMSO) was assessed. Radioactivity was measured in skin and receiver compartments. Three approaches were used to visualize activity in skin including the recent iQID technique for quantification. Transfer of Am was 24-fold greater than Pu and Pu-TBP complex penetration was enhanced by 500-fold. Actinide-DTPA transfer was greater than the Am or Pu alone (17-fold and 148-fold, respectively). The stratum corneum retained the majority of activity in all cases and both DMSO and TBP enhanced skin retention of Am and Pu, respectively. Histological and bioimaging data confirmed these results and the iQID camera allowed the quantification of skin activity. Skin penetration and fixation profiles are different depending on the chemical actinide form. Altered behavior of Pu-TBP and actinide-DTPA complexes reinforces the need to address decontamination protocols.

  4. Human skin penetration of silver nanoparticles through intact and damaged skin.

    Science.gov (United States)

    Larese, Francesca Filon; D'Agostin, Flavia; Crosera, Matteo; Adami, Gianpiero; Renzi, Nadia; Bovenzi, Massimo; Maina, Giovanni

    2009-01-01

    There is a growing interest on nanoparticle safety for topical use. The benefits of nanoparticles have been shown in several scientific fields, but little is known about their potential to penetrate the skin. This study aims at evaluating in vitro skin penetration of silver nanoparticles. Experiments were performed using the Franz diffusion cell method with intact and damaged human skin. Physiological solution was used as receiving phase and 70 microg/cm2 of silver nanoparticles coated with polyvinylpirrolidone dispersed in synthetic sweat were applied as donor phase to the outer surface of the skin for 24h. The receptor fluid measurements were performed by electro thermal atomic absorption spectroscopy (ETAAS). Human skin penetration was also determined by using transmission electron microscope (TEM) to verify the location of silver nanoparticles in exposed membranes. Median silver concentrations of 0.46 ng cm(-2) (range skin (eight cells) and on damaged skin (eight cells), respectively. Twenty-four hours silver flux permeation in damaged skin was 0.62+/-0.2 ng cm(-2) with a lag time <1h. Our experimental data showed that silver nanoparticles absorption through intact and damaged skin was very low but detectable, and that in case of damaged skin it was possible an increasing permeation of silver applied as nanoparticles. Moreover, silver nanoparticles could be detected in the stratum corneum and the outermost surface of the epidermis by electron microscopy. We demonstrated for the first time that silver applied as nanoparticles coated with polyvinylpirrolidone is able to permeate the damaged skin in an in vitro diffusion cell system.

  5. Identification of a novel skin penetration enhancement peptide by phage display peptide library screening.

    Science.gov (United States)

    Kumar, Sunny; Sahdev, Preety; Perumal, Omathanu; Tummala, Hemachand

    2012-05-07

    Skin is an important site for local or systemic application of drugs. However, a majority of drugs have poor permeability through the skin's topmost layer, stratum corneum (SC). The aim of this study was to identify safe and smaller peptides that could enhance the skin penetration of drug molecules. By screening phage display peptide library, we have identified a T2 peptide (LVGVFH), which enhanced the penetration of bacteriophages (~800 nm long bacterial viruses) across porcine and mouse skin. Pretreating the skin with synthetic T2 peptide at pH 4.5 resulted in significant penetration enhancement of hydrophilic drug 5-fluorouracil (5-FU) across skin. FTIR spectroscopy showed that the T2 peptide interacted with skin lipids to enhance the skin penetration. Pretreating the skin with T2 peptide enhanced the partitioning of small molecules with different lipophilicities (5-FU, fluorescein isothiocyanate, and rhodamine 123 hydrochloride) into skin. Fluorescence studies showed that T2 peptide enhanced the diffusion of these molecules into intercellular lipids of SC and thus enhanced the penetration into the skin. Histidine at the c-terminus of T2 peptide was identified to be critical for the skin penetration enhancement. T2 peptide interacted with skin lipids to cause skin penetration enhancement. The study identified a novel, safe, and noninvasive peptide to improve the skin penetration of drugs without chemical conjugation.

  6. Prediction of Skin Penetration using Artificial Neural Network

    Directory of Open Access Journals (Sweden)

    Sangita Saini,

    2010-06-01

    Full Text Available The artificial neural networks (ANN technologies provide on-line capability to analyze many inputs and provide information to multiple outputs, and have the capability to learn or adapt to changing conditions. No doubt that the determination of Skin permeability is a time consuming process; which involves a quite tedious work. Material and method: Software Neurodimension was used for this study. A data set was taken from literature and used to train the network. A set of 20 compounds were used to construct the ANN models for training and 10 compounds used for prediction of skin penetration (n=30, molecular weight>500 da. Skin permeability expressed in log Kp (cm/h. Abraham descriptors of R2 (excess molar refraction, π2 H dipolarity/polarizability, Σα2 H, Σβ2 H (the overall or effective hydrogen-bond acidity and basicity, and Vx (the McGowan haracteristic volume were obtained. Result: The correlation between the skin permeability coefficient and the Abraham descriptors were obtained from the trained neural network. The regression coefficient was 0.856 for training subset and MSE was 0.04. In addition, thepredictability of the neural network model was compared to the experimental data. This paper uses artificial neural network for prediction of Skin permeability study.

  7. Comparative analysis of the effects of CO2 fractional laser and sonophoresis on human skin penetration with 5-aminolevulinic acid.

    Science.gov (United States)

    Choi, J H; Shin, E J; Jeong, K H; Shin, M K

    2017-08-19

    Successful delivery of a photosensitizer into the skin is an important factor for effective photodynamic therapy (PDT). The effective method to increase drug penetration within short incubation time overcoming skin barrier have been investigated. This study was performed to analyze and compare the effectiveness of ablative fractional laser (FXL) pretreatment and/or sonophoresis for enhancing the penetration of 5-aminolevulinic acid (ALA) into human skin in vivo. Twenty-four identical 1 × 1 cm(2) treatment areas were mapped on the backs of ten healthy male subjects. Each area received FXL pretreatment and/or sonophoresis with different energy settings and ALA incubation times. After treatments, porphyrin fluorescence reflecting the ALA penetration were measured. Application of ablative CO2 FXL pretreatment resulted to higher fluorescence intensities than the non-treatment group. Incubation times were positively correlated with the increments of ALA penetration. However, increasing pulse energy or combining with sonophoresis did not show additional positive effects on ALA penetration. Ablative CO2 FXL pretreatment effectively facilitated ALA penetration in human skin in vivo. Ablative CO2 FXL alone without sonophoresis setting pulse energy of 10 and 20 mJ with more than 60 min of ALA incubation time could be an ideal setting for ALA penetration.

  8. Human skin penetration of cobalt nanoparticles through intact and damaged skin.

    Science.gov (United States)

    Larese Filon, Francesca; Crosera, Matteo; Timeus, Elisa; Adami, Gianpiero; Bovenzi, Massimo; Ponti, Jessica; Maina, Giovanni

    2013-02-01

    Cobalt nanoparticles (CoNPs) are produced for several industrial and biomedical applications but there is a lack of data on human cutaneous absorption. Cobalt is also a skin sensitizer that can cause allergic contact dermatitis. Co applied as NPs, due to their small size and high surface, can penetrate into the skin in higher amount that bulk material. The aim of this study was to evaluate the absorption of Co applied as NPs in both intact and damaged skin. Experiments were performed using Franz cells and 1.0 mg cm(-2) of CoNPs was applied as donor phase for 24h. Mean Co content of 8.5 ± 1.2 ng cm(-2) and 1.87 ± 0.86 μg cm(-2) were found in the receiving solutions of Franz cells when the CoNPs suspension was applied on intact skin and on damaged skin, respectively. Twenty-four hours Co flux permeation was 76 ± 49 ng cm(-2)h(-1) in damaged skin with a lag time of 2.8 ± 2.1h. This study suggests that Co applied as NPs is able to penetrate the human skin in an in vitro diffusion cell system.

  9. Ex vivo penetration of low-level laser light through equine skin and flexor tendons.

    Science.gov (United States)

    Duesterdieck-Zellmer, Katja F; Larson, Maureen K; Plant, Thomas K; Sundholm-Tepper, Andrea; Payton, Mark E

    2016-09-01

    OBJECTIVE To measure penetration efficiencies of low-level laser light energy through equine skin and to determine the fraction of laser energy absorbed by equine digital flexor tendons (superficial [SDFT] and deep [DDFT]). SAMPLE Samples of skin, SDFTs, and DDFTs from 1 metacarpal area of each of 19 equine cadavers. PROCEDURES A therapeutic laser with wavelength capabilities of 800 and 970 nm was used. The percentage of energy penetration for each wavelength was determined through skin before and after clipping and then shaving of hair, through shaved skin over SDFTs, and through shaved skin, SDFTs, and DDFTs (positioned in anatomically correct orientation). Influence of hair color; skin preparation, color, and thickness; and wavelength on energy penetration were assessed. RESULTS For haired skin, energy penetration was greatest for light-colored hair and least for dark-colored hair. Clipping or shaving of skin improved energy penetration. Light-colored skin allowed greatest energy penetration, followed by medium-colored skin and dark-colored skin. Greatest penetration of light-colored skin occurred with the 800-nm wavelength, whereas greatest penetration of medium- and dark-colored skin occurred with the 970-nm wavelength. As skin thickness increased, energy penetration of samples decreased. Only 1% to 20% and 0.1% to 4% of energy were absorbed by SDFTs and DDFTs, respectively, depending on skin color, skin thickness, and applied wavelength. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that most laser energy directed through equine skin was absorbed or scattered by the skin. To achieve delivery of energy doses known to positively affect cells in vitro to equine SDFTs and DDFTs, skin preparation, color, and thickness and applied wavelength must be considered.

  10. Mechanics of Stabbing: Biaxial Measurement of Knife Stab Penetration of Skin Simulant

    CERN Document Server

    Gilchrist, Michael D; Curtis, Michael; Cassidy, Mary; Byrne, Greg; Destrade, Michel; 10.1016/j.forsciint.2007.10.010

    2008-01-01

    In medicolegal situations, the consequences of a stabbing incident are described in terms that are qualitative without being quantitative. Here, the mechanical variables involved in knife-tissue penetration events are used to determine the parameters needed to be controlled in a measurement device. They include knife geometry, in-plane mechanical stress state of skin, angle and speed of knife penetration, and underlying fascia. Four household knives with different geometries were used. Synthetic materials were used to simulate the response of skin, fat and cartilage: polyurethane, foam, and ballistic soap, respectively. The force and energy applied by the blade and the skin displacement were used to identify skin penetration. The skin tension is shown to have a direct effect on the force and energy for knife penetration and on the depth of displacement of the simulant prior to penetration: larger levels of in-plane tension in the skin are associated with lower penetration forces, energies and displacements. L...

  11. Measuring skin penetration by confocal Raman microscopy (CRM): correlation to results from conventional experiments

    Science.gov (United States)

    Lunter, Dominique; Daniels, Rolf

    2016-03-01

    Confocal Raman microscopy has become an advancing technique in the characterization of drug transport into the skin. In this study the skin penetration of a local anesthetic from a semisolid preparation was investigated. Furthermore, the effect of the chemical enhancers propylene glycol and POE-23-lauryl ether on its penetration was investigated. The results show that confocal Raman microscopy may provide detailed information on the penetration of APIs into the skin and may elucidate their distribution within the skin with high resolution. The results of the CRM analysis are fully in line with those of conventional permeation and penetration experiments.

  12. Human skin penetration of gold nanoparticles through intact and damaged skin.

    Science.gov (United States)

    Filon, Francesca Larese; Crosera, Matteo; Adami, Gianpiero; Bovenzi, Massimo; Rossi, Federica; Maina, Giovanni

    2011-12-01

    Gold nanoparticles (AuNPs) are produced for many applications but there is a lack of available data on their skin absorption. Experiments were performed using the Franz diffusion cell method with intact and damaged human skin. A physiological solution was used as receiving phase and 0.5 mL (1st exp) and 1.5 mL (2nd exp) of a solution containing 100 mg L⁻¹ of AuNPs (15 and 45 μg cm⁻², respectively) was applied as donor phase to the outer surface of the skin for 24 h. Skin absorption was dose dependent. Mean gold content of 214.0 ± 43.7 ng cm⁻² and 187.7 ± 50.2 ng cm⁻² were found in the receiving solutions of cells where the AuNPs solution was applied in higher concentration on intact skin (8 Franz cells) and on damaged skin (8 Franz cells), respectively. Twenty-four hours gold flux permeation was 7.8 ± 2.0 ng cm⁻² h⁻¹ and 7.1 ± 2.5 ng cm⁻² h⁻¹ in intact and damaged skin, respectively, with a lag time less than 1 hour. Transmission Electron Microscope analysis on skin samples and chemical analysis using Inductively Coupled Plasma-Mass Spectrometry demonstrated the presence of AuNPs into epidermis and dermis. This study showed that AuNPs are able to penetrate the human skin in an in vitro diffusion cell system.

  13. Effects of Various Penetration Enhancers on Penetration of Aminophylline Through Shed Snake Skin

    Science.gov (United States)

    Kouchak, Maryam; Handali, Somayeh

    2014-01-01

    Background: Cellulite is the accumulation of subcutaneous fat and connective tissue in tights and buttocks. Xanthines, such as aminophylline, are used as phosphodiesterase inhibitors, and are also adenosine receptor antagonists. Objectives: The aim of the present study was to characterize in vitro aminophylline transdermal absorption through shed snake skin, and to investigate the absorption enhancing effect of various enhancers. Materials and Methods: Aminophylline gels were prepared using theophylline and ethylenediamine as raw materials of aminophylline, hydroxypropyl methyl cellulose (HPMC) F4M as gelling agent, and propylene glycol as a co-solvent. Sodium tauroglycocholate (STGC) (100, 200, and 500 μg/mL), lauric acid (1.7 and 15%), and ethanol (60%) were added as enhancers. In vitro percutaneous absorption experiments were performed on snake skin using Franz diffusion cells. Flux (J), permeability coefficient (P), and enhancement factor (EF) for each formulation were calculated. Results: The results indicated that all of enhancers significantly enhanced drug permeability. This effect was decreased by increasing the concentration of STGC; in contrast, by increasing the concentration of lauric acid from 1.7 to 15%, EF was enhanced Although ethanol (60%) and STGC (100 μg/mL) showed the highest EFs, the effect of ethanol on drug permeability appeared with a lag time. Conclusions: According to the findings, type and concentration of penetration enhancers can effect on transdermal permeation of drug. PMID:24644435

  14. Storage Conditions of Skin Affect Tissue Structure and Subsequent in vitro Percutaneous Penetration

    DEFF Research Database (Denmark)

    Nielsen, J B; Plasencia, I; Sørensen, J A

    2011-01-01

    fluorescence microscopy) and in vitro percutaneous penetration of caffeine under four different storage conditions using skin samples from the same donors: fresh skin, skin kept at -20°C for 3 weeks (with or without the use of polyethylene glycol) and at -80°C. Our results show a correlation between increasing...

  15. Quantification of skin penetration of antioxidants of varying lipophilicity.

    Science.gov (United States)

    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.

  16. Glove material, reservoir formation, and dose affect glove permeation and subsequent skin penetration

    DEFF Research Database (Denmark)

    Nielsen, Jesper Bo; Sørensen, Jens Ahm

    2012-01-01

    cell to evaluate overall penetration through glove and skin as well as the deposition in the different reservoirs. Benzoic acid was applied on latex or nitrile gloves placed on top of human skin. The amounts of chemical were quantified in the glove material, between glove and skin, within the skin......, and in the receptor chamber. Both glove materials reduce total penetration of benzoic acid, but nitrile gloves offer a significantly better protection than latex gloves. This difference was less pronounced at the higher of the two concentrations of benzoic acid applied. Thus, glove types that offer relevant...

  17. Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation.

    Science.gov (United States)

    Ali, Niwa; Zirak, Bahar; Rodriguez, Robert Sanchez; Pauli, Mariela L; Truong, Hong-An; Lai, Kevin; Ahn, Richard; Corbin, Kaitlin; Lowe, Margaret M; Scharschmidt, Tiffany C; Taravati, Keyon; Tan, Madeleine R; Ricardo-Gonzalez, Roberto R; Nosbaum, Audrey; Bertolini, Marta; Liao, Wilson; Nestle, Frank O; Paus, Ralf; Cotsarelis, George; Abbas, Abul K; Rosenblum, Michael D

    2017-06-01

    The maintenance of tissue homeostasis is critically dependent on the function of tissue-resident immune cells and the differentiation capacity of tissue-resident stem cells (SCs). How immune cells influence the function of SCs is largely unknown. Regulatory T cells (Tregs) in skin preferentially localize to hair follicles (HFs), which house a major subset of skin SCs (HFSCs). Here, we mechanistically dissect the role of Tregs in HF and HFSC biology. Lineage-specific cell depletion revealed that Tregs promote HF regeneration by augmenting HFSC proliferation and differentiation. Transcriptional and phenotypic profiling of Tregs and HFSCs revealed that skin-resident Tregs preferentially express high levels of the Notch ligand family member, Jagged 1 (Jag1). Expression of Jag1 on Tregs facilitated HFSC function and efficient HF regeneration. Taken together, our work demonstrates that Tregs in skin play a major role in HF biology by promoting the function of HFSCs. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Influence of massage and occlusion on the ex vivo skin penetration of rigid liposomes and invasomes

    DEFF Research Database (Denmark)

    Trauer, S.; Richter, H.; Kuntsche, Judith

    2014-01-01

    Liposomes are frequently described as drug delivery systems for dermal and transdermal applications. Recently, it has been shown that particulate substances penetrate effectively into hair follicles and that the follicular penetration depth can be increased by massaging the skin, which simulates...... the in vivo movement of hairs in the hair follicles. In the present study, massage was applied to skin mounted to Franz diffusion cells. By means of confocal laser scanning microscopy, the influence of massage and occlusion on the follicular penetration depths of rigid and flexible liposomes loaded...... with a hydrophilic and lipophilic dye was investigated. The application of massage increased follicular penetration significantly. Occlusion resulted in an increased follicular penetration depth only for rigid liposomes, whereas invasomes did not penetrate more effectively if occlusion was applied. The results...

  19. Ethnic differences in skin physiology, hair follicle morphology and follicular penetration

    OpenAIRE

    Luther, Natalie

    2012-01-01

    There is increasing evidence that different ethnic groups exhibit varieties in skin physiological parameters and penetration behaviour, although data available are inconsistent. Likewise variations in hair follicle morphology have been described although its influence on the follicular penetration process has not been investigated until now. Therefore, the aim of the present study was to investigate skin physiological parameters, the hair follicle morphology and the follicular and interce...

  20. Assessment of Quantum Dot Penetration into Skin in Different Species Under Different Mechanical Actions

    Science.gov (United States)

    Monteiro-Riviere, N. A.; Zhang, L. W.

    Skin penetration is one of the major routes of exposure for nanoparticles to gain access to a biological system. QD nanoparticles have received a great deal of attention due to their fluorescent characteristics and potential use in medical applications. However, little is known about their permeability in skin. This study focuses on three types of quantum dots (QD) with different surface coatings and concentrations on their ability to penetrate skin. QD621 (polyethylene glycol coated, PEG) was studied for 24 h in porcine skin flow-through diffusion cells. QD565 and QD655 coated with carboxylic acid were studied for 8 and 24 h in flow-through diffusion cells with flexed, tape stripped and abraded rat skin to determine if these mechanical actions could perturb the barrier and affect penetration. Confocal microscopy depicted QD621 penetration through the uppermost layers of the stratum corneum (SC) and fluorescence was found in the SC and near hair follicles. QD621 were found in the intercellular lipid layers of the SC by transmission electron microscopy (TEM). QD565 and 655 with flexed and tape-stripped skin did not show penetration; only abraded skin showed penetration in the viable dermal layers. In all QD studies, inductively coupled plasma-optical emission spectroscopy (ICP-OES) analysis for cadmium (Cd) and fluorescence for QD did not detect Cd or fluorescence signal in the perfusate at any time point, concentration or type of QD. These results indicate that porcine skin penetration of QD621 is minimal and limited primarily to the outer SC layers, while QD565 and 655 penetrated into the dermis of abraded skin. The anatomical complexity of skin and species differences should be taken into consideration when selecting an animal model to study nanoparticle absorption/penetration. These findings are of importance to risk assessment for nanoscale materials because it indicates that if skin barrier is altered such as in wounds, scrapes, or dermatitis conditions could

  1. 31P Solid-state NMR based monitoring of permeation of cell penetrating peptides into skin

    Science.gov (United States)

    Desai, Pinaki R.; Cormier, Ashley R.; Shah, Punit P.; Patlolla, Ram R.; Paravastu, Anant K.; Singh, Mandip

    2013-01-01

    The main objective of the current study was to investigate penetration of cell penetrating peptides (CPPs: TAT, R8, R11 and YKA) through skin intercellular lipids using 31P magic angle spinning (MAS) solid-state NMR. In vitro skin permeation studies were performed on rat skin, sections (0–60, 61–120 and 121–180 µm) were collected and analyzed for 31P NMR signal. The concentration dependent shift of 0, 25, 50, 100 and 200 mg/ml of TAT on skin layers, diffusion of TAT, R8, R11 and YKA in the skin and time dependent permeation of R11 was measured on various skin sections using 31P solid-state NMR. Further, CPPs and CPP-tagged fluorescent dye encapsulate liposomes (FLip) in skin layers were tagged using confocal microscopy. The change in 31P NMR chemical shift was found to depend monotonically on the amount of CPP applied on skin, with saturation behavior above 100 mg/ml CPP concentration. R11 and TAT caused more shift in solid-state NMR peaks compared to other peptides. Furthermore, NMR spectra showed R11 penetration up to 180 µm within 30 min. The results of the solid-state NMR study were in agreement with confocal microscopy studies. Thus, 31P solid-state NMR can be used to track CPP penetration into different skin layers. PMID:23702274

  2. Further development of an in vitro model for studying the penetration of chemicals through compromised skin.

    Science.gov (United States)

    Davies, Diane J; Heylings, Jon R; Gayes, Heather; McCarthy, Timothy J; Mack, M Catherine

    2017-02-01

    A new in vitro model based on the electrical resistance properties of the skin barrier has been established in this laboratory. The model utilises a tape stripping procedure in dermatomed pig skin that removes a specific proportion of the stratum corneum, mimicking impaired barrier function observed in humans with damaged skin. The skin penetration and distribution of chemicals with differing physicochemical properties, namely; Benzoic acid, 3-Aminophenol, Caffeine and Sucrose has been assessed in this model. Although, skin penetration over 24h differed for each chemical, compromising the skin did not alter the shape of the time course profile, although absorption into receptor fluid was higher for each chemical. Systemic exposure (receptor fluid, epidermis and dermis), was marginally higher in compromised skin following exposure to the fast penetrant, Benzoic acid, and the slow penetrant Sucrose. The systemically available dose of 3-Aminophenol increased to a greater extent and the absorption of Caffeine was more than double in compromised skin, suggesting that Molecular Weight and Log Pow, are not the only determinants for assessing systemic exposure under these conditions. Although further investigations are required, this in vitro model may be useful for prediction of dermal route exposure under conditions where skin barrier is impaired.

  3. (31)P solid-state NMR based monitoring of permeation of cell penetrating peptides into skin.

    Science.gov (United States)

    Desai, Pinaki R; Cormier, Ashley R; Shah, Punit P; Patlolla, Ram R; Paravastu, Anant K; Singh, Mandip

    2014-02-01

    The main objective of the current study was to investigate penetration of cell penetrating peptides (CPPs: TAT, R8, R11, and YKA) through skin intercellular lipids using (31)P magic angle spinning (MAS) solid-state NMR. In vitro skin permeation studies were performed on rat skin, and sections (0-60, 61-120, and 121-180μm) were collected and analyzed for (31)P NMR signal. The concentration-dependent shift of 0, 25, 50, 100, and 200mg/ml of TAT on skin layers, diffusion of TAT, R8, R11, and YKA in the skin and time dependent permeation of R11 was measured on various skin sections using (31)P solid-state NMR. Further, CPPs and CPP-tagged fluorescent dye encapsulate liposomes (FLip) in skin layers were tagged using confocal microscopy. The change in (31)P NMR chemical shift was found to depend monotonically on the amount of CPP applied on skin, with saturation behavior above 100mg/ml CPP concentration. R11 and TAT caused more shift in solid-state NMR peaks compared to other peptides. Furthermore, NMR spectra showed R11 penetration up to 180μm within 30min. The results of the solid-state NMR study were in agreement with confocal microscopy studies. Thus, (31)P solid-state NMR can be used to track CPP penetration into different skin layers. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Cationic membrane-active peptides - anticancer and antifungal activity as well as penetration into human skin.

    Science.gov (United States)

    Do, Nhung; Weindl, Günther; Grohmann, Lisa; Salwiczek, Mario; Koksch, Beate; Korting, Hans Christian; Schäfer-Korting, Monika

    2014-05-01

    Cationic antimicrobial peptides are ancient natural broad-spectrum antibiotics, and several compounds also exhibit anticancer activity. However, most applications pertain to bacterial infections, and treatment for skin cancer is less frequently considered. The cytotoxicity of melittin, cecropin A, protegrin-1 and histatin 5 against squamous skin cancer cell lines and normal human keratinocytes was evaluated and compared to established drugs. The results show that melittin clearly outperforms 5-fluorouracil regarding antitumor activity. Importantly, combined melittin and 5-fluorouracil enhanced cytotoxic effects on cancer cells and reduced toxicity on normal keratinocytes. Additionally, minimum inhibitory concentrations indicate that melittin also shows superior activity against clinical and laboratory strains of Candida albicans compared to amphotericin B. To evaluate its potential for topical applications, human skin penetration of melittin was investigated ex vivo and compared to two non-toxic cell-penetrating peptides (CPPs), low molecular weight protamine (LMWP) and penetratin. The stratum corneum prevents penetration into viable epidermis over 6 h; however, the peptides gain access to the viable skin after 24 h. Inhibition of digestive enzymes during skin penetration significantly enhances the availability of intact peptide. In conclusion, melittin may represent an innovative agent for non-melanoma skin cancer and infectious skin diseases. In order to develop a drug candidate, skin absorption and proteolytic digestion by skin enzymes need to be addressed. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. The effects of surfactants on penetration across the skin*.

    Science.gov (United States)

    Walters, K A; Bialik, W; Brain, K R

    1993-12-01

    Synopsis Many of the properties of surfactants can be related to their ability to concentrate at phase interfaces, leading to a reduction in interracial tension. In biological systems the effects of surfactants are complex, particularly their effect on cell and other membranes, and this can lead to alterations in permeability characteristics. This is of particular relevance when considering the stratum corneum which has long been recognized as the major barrier to skin permeation. The magnitude of skin barrier function alteration is dependent on surfactant structure, both the hydrophobic alkyl chain and the hydropnilic ethylene oxide chain demonstrating some structure-activity behaviour. In many biological systems, including skin, surfactants with a similar hydrophilic group will show maximum membrane activity if they possess a decyl or dodecyl alkyl chain. It is difficult to rationalise this phenomenon, given that such solution properties as partition coefficients and CMCs do not show maxima or minima at these chain lengths. It may be that the physical parameters and molecular dimensions of the decyl/dodecyl chain provide the optimal ability to intercalate with the lipid bilayer structure. There is little doubt that once the surfactant has intercalated with the lipid bilayers in the lamellar liquid crystals of the stratum corneum, fluidity in the hydrophobic regions is increased. Effectively, this leads to a looser, more permeable structure. The significance of data obtained using commercially available surfactants, however, can be questioned on the grounds of purity. The purpose of this review is to describe some of the methods used to evaluate the effects of surfactants on the skin barrier and to discuss recent attempts to predict surfactant action on the skin using various biological and physical techniques. Résumé La plupart des propriétés des surfactants dépend de leur facilitéà se concentrer aux interfaces, menant ainsi à la réduction de la tension

  6. Size dependent skin penetration of nanoparticles in murine and porcine dermatitis models.

    Science.gov (United States)

    Try, Céline; Moulari, Brice; Béduneau, Arnaud; Fantini, Oscar; Pin, Didier; Pellequer, Yann; Lamprecht, Alf

    2016-03-01

    A major limitation in the current topical treatment of inflammatory skin diseases is the inability to selectively deliver the drug to the inflammation site. Recently, smart drug delivery systems such as nanocarriers are being investigated to enhance the selective deposition of anti-inflammatory drugs in inflamed areas of the skin to achieve higher therapeutic efficacy with minimal side effects. Of such systems, polymeric nanoparticles are considered very efficient carriers for the topical drug delivery. In the current work, poly(l-lactide-co-glycolide) nanoparticles of nominal sizes of 70nm (NP70) and 300nm (NP300) were studied for their intra-epidermal distribution in murine and pig atopic dermatitis models over time against the respective healthy controls. Confocal laser scanning microscopical examination of skin biopsies was utilized for the qualitative and semi-quantitative analyses of nanoparticles skin deposition and penetration depth. While no skin penetration was found for any of the particles in healthy skin, the accumulation of NP70 was significantly higher than NP300 in inflamed skin (15-fold in mice, 5-fold in pigs). Penetration depth of NP70 decreased over time in mice from 55±3μm to 20±2μm and similar tendencies were observed for the other formulations. In inflamed pig skin, a similar trend was found for the penetration depth (NP70: 46±12μm versus NP300: 23±3μm); however, the NP amount remained constant for the whole analyzed period. Their ability to penetrate specifically into inflamed skin combined with minimal effects on healthy skin underlines small polymeric nanoparticles' potential as selective drug carriers in future treatment of chronic inflammatory skin diseases such as atopic dermatitis.

  7. Studies on percutaneous penetration of chemicals - Impact of storage conditions for excised human skin.

    Science.gov (United States)

    Dennerlein, Kathrin; Schneider, Désirée; Göen, Thomas; Schaller, Karl Heinz; Drexler, Hans; Korinth, Gintautas

    2013-03-01

    According to international guidelines skin penetration experiments can be carried out using freshly excised or frozen stored skin. However, this recommendation refers to data obtained in experiments with human cadaver skin. In our study, the percutaneous penetration of the occupationally relevant chemicals anisole, cyclohexanone and 1,4-dioxane was investigated for freshly excised as well as for 4 and 30 days at -20°C stored human skin using the diffusion cell technique. As indicator for the impairment of skin barrier by freezing cholesterol dissolution was determined in the solvents in exposure chambers of diffusion cells. Considering the percutaneously penetrated amounts, the following ranking was determined: 1,4-dioxane>anisole>cyclohexanone (decline to a factor of 5.9). The differences of fluxes between freshly excised and frozen stored skin (4 and 30 days) were not significant (p>0.05). Cholesterol dissolved from the skin indicates no significant differences between freshly excised and frozen stored skin. This study shows that freezing of human skin for up to 30 days does not alter the skin barrier function and the permeability of chemicals.

  8. Interactions of skin thickness and physicochemical properties of test compounds in percutaneous penetration studies

    NARCIS (Netherlands)

    Wilkinson, S.C.; Maas, W.J.M.; Nielsen, J.B.; Greaves, L.C.; Sandt, J.J.M. van de; Williams, F.M.

    2006-01-01

    Objectives: To determine the effect of skin thickness on the percutaneous penetration and distribution of test compounds with varying physicochemical properties using in vitro systems. Studies were carried out in accordance with OECD guidelines on skin absorption tests. Methods: Percutaneous penetra

  9. Release of rosmarinic acid from semisolid formulations and its penetration through human skin ex vivo

    Directory of Open Access Journals (Sweden)

    Stelmakienė Ada

    2015-06-01

    Full Text Available The aim of this study was to evaluate the release of rosmarinic acid (RA from the experimental topical formulations with the Melissa officinalis L. extract and to evaluate its penetration through undamaged human skin ex vivo. The results of the in vitro release study showed that higher amounts of RA were released from the emulsion vehicle when lemon balm extract was added in its dry form. An inverse correlation was detected between the released amount of RA and the consistency index of the formulation. Different penetration of RA into the skin may be influenced by the characteristics of the vehicle as well as by the form of the extract. The results of penetration assessment showed that the intensity of RA penetration was influenced by its lipophilic properties: RA was accumulating in the epidermis, while the dermis served as a barrier, impeding its deeper penetration.

  10. Pig and guinea pig skin as surrogates for human in vitro penetration studies: a quantitative review.

    Science.gov (United States)

    Barbero, Ana M; Frasch, H Frederick

    2009-02-01

    Both human and animal skin in vitro models are used to predict percutaneous penetration in humans. The objective of this review is a quantitative comparison of permeability and lag time measurements between human and animal skin, including an evaluation of the intra and inter species variability. We limit our focus to domestic pig and rodent guinea pig skin as surrogates for human skin, and consider only studies in which both animal and human penetration of a given chemical were measured jointly in the same lab. When the in vitro permeability of pig and human skin were compared, the Pearson product moment correlation coefficient (r) was 0.88 (Pskin permeability of 21% for pig and 35% for human, and an inter species average coefficient of variation of 37% for the set of studied compounds (n=41). The lag times of pig skin and human skin did not correlate (r=0.35, P=0.26). When the in vitro permeability of guinea pig and human skin were compared, r=0.96 (Phuman, and an inter species coefficient of variation of permeability of 41% for the set of studied compounds (n=15). Lag times of guinea pig and human skin correlated (r=0.90, Phuman skin was calculated for pig skin (n=50) and guinea pig skin (n=25). For pig skin, 80% of measurements fell within the range 0.3skin, 65% fell within that range. Both pig and guinea pig are good models for human skin permeability and have less variability than the human skin model. The skin model of choice will depend on the final purpose of the study and the compound under investigation.

  11. Advances in Skin Substitutes—Potential of Tissue Engineered Skin for Facilitating Anti-Fibrotic Healing

    Directory of Open Access Journals (Sweden)

    Mathew Varkey

    2015-07-01

    Full Text Available Skin protects the body from exogenous substances and functions as a barrier to fluid loss and trauma. The skin comprises of epidermal, dermal and hypodermal layers, which mainly contain keratinocytes, fibroblasts and adipocytes, respectively, typically embedded on extracellular matrix made up of glycosaminoglycans and fibrous proteins. When the integrity of skin is compromised due to injury as in burns the coverage of skin has to be restored to facilitate repair and regeneration. Skin substitutes are preferred for wound coverage when the loss of skin is extensive especially in the case of second or third degree burns. Different kinds of skin substitutes with different features are commercially available; they can be classified into acellular skin substitutes, those with cultured epidermal cells and no dermal components, those with only dermal components, and tissue engineered substitutes that contain both epidermal and dermal components. Typically, adult wounds heal by fibrosis. Most organs are affected by fibrosis, with chronic fibrotic diseases estimated to be a leading cause of morbidity and mortality. In the skin, fibroproliferative disorders such as hypertrophic scars and keloid formation cause cosmetic and functional problems. Dermal fibroblasts are understood to be heterogeneous; this may have implications on post-burn wound healing since studies have shown that superficial and deep dermal fibroblasts are anti-fibrotic and pro-fibrotic, respectively. Selective use of superficial dermal fibroblasts rather than the conventional heterogeneous dermal fibroblasts may prove beneficial for post-burn wound healing.

  12. Human skin penetration and local effects of topical nano zinc oxide after occlusion and barrier impairment.

    Science.gov (United States)

    Leite-Silva, V R; Sanchez, W Y; Studier, H; Liu, D C; Mohammed, Y H; Holmes, A M; Ryan, E M; Haridass, I N; Chandrasekaran, N C; Becker, W; Grice, J E; Benson, H A E; Roberts, M S

    2016-07-01

    Public health concerns continue to exist over the safety of zinc oxide nanoparticles that are commonly used in sunscreen formulations. In this work, we assessed the effects of two conditions which may be encountered in everyday sunscreen use, occlusion and a compromised skin barrier, on the penetration and local toxicity of two topically applied zinc oxide nanoparticle products. Caprylic/capric triglyceride (CCT) suspensions of commercially used zinc oxide nanoparticles, either uncoated or with a silane coating, were applied to intact and barrier impaired skin of volunteers, without and with occlusion for a period of six hours. The exposure time was chosen to simulate normal in-use conditions. Multiphoton tomography with fluorescence lifetime imaging was used to noninvasively assess zinc oxide penetration and cellular metabolic changes that could be indicative of toxicity. We found that zinc oxide nanoparticles did not penetrate into the viable epidermis of intact or barrier impaired skin of volunteers, without or with occlusion. We also observed no apparent toxicity in the viable epidermis below the application sites. These findings were validated by ex vivo human skin studies in which zinc penetration was assessed by multiphoton tomography with fluorescence lifetime imaging as well as Zinpyr-1 staining and toxicity was assessed by MTS assays in zinc oxide treated skin cryosections. In conclusion, applications of zinc oxide nanoparticles under occlusive in-use conditions to volunteers are not associated with any measurable zinc oxide penetration into, or local toxicity in the viable epidermis below the application site.

  13. Storage conditions of skin affect tissue structure and in vitro percutaneus penetration

    DEFF Research Database (Denmark)

    Nielsen, Jesper Bo; Bagatolli, Luis

    2016-01-01

    skin at -20oC causes structural changes in the upper Stratum Corneum observable with image techniques such as multiphoton excitation fluorescence microscopy. The presently available literature does, however, not support that the observed structural damage to the integrity is sufficient to cause......For logistic and practical reasons it is difficult to perform in vitro studies on percutaneous penetration on fresh human skin obtained directly from surgery. Skin samples are therefore often kept frozen until use. The present chapter present the available literature on the topic. Storage of human...... structural changes in upper as well as deeper parts of Stratum Corneum. These more severe changes corresponds to significantly increased percutaneous penetration of chemicals applied to skin specimens stored at very low temperatures. Storage of human skin for later use in in vitro studies on percutaneous...

  14. Polymeric Nanocapsules and Lipid-Core Nanocapsules Have Diverse Skin Penetration.

    Science.gov (United States)

    de Brum, Tainá L; Fiel, Luana A; Contri, Renata V; Guterres, Sílvia S; Pohlmann, Adriana R

    2015-01-01

    Biodegradable nanoparticles have been widely studied as drug carriers in order to increase drug solubility in aqueous media, modify biodistribution, target tissues and organs or control the drug release. Those nanoparticles are, in general, produced as liquid formulations to act as final dosage forms or as intermediate for solid or semi-solid products. Considering the dermatological applications, as medicines or cosmetics, different nanoparticles have been proposed to control the skin penetration of encapsulated lipophilic substances. A point rarely investigated is the penetration of the carrier itself into the skin, independent of the drug penetration profile. In this way, our objective was to correlate the flexibility of the biodegradable nanoparticles to the depth of their skin penetration. To minimize the impact of the chemical composition, the surface chemistry or the shape and size distribution on the results, two kinds of polymeric nanocapsules presenting diverse mechanical properties were produced using almost the same materials and their concentrations. The nanocapsules (NC) and the lipid-core nanocapsules (LNC) were prepared by solvent displacement using Rhodamine B-labeled polymer, oil and surfactants. The only difference in composition between them is the presence of sorbitan monostearate in the latter which was used to have a more rigid nanoparticle as previously reported. NC and LNC had, respectively, mean diameters of 178 and 180 nm and zeta potentials of -11 and -9 mV. The in vitro skin penetration was carried out using Franz cells (pig skin as membrane). Skin samples were observed by confocal laser scanning microscopy (CLSM). NC reached the dermis, while LNC was retained at the outermost layers of the skin. The result was in accordance with the flexibility previously determined for those nanocapsules, in a way that higher flexibility gives deeper penetration. NC can reach the dermis and LNC can act as reservoir systems at the epidermis.

  15. Influence of anatomical site and topical formulation on skin penetration of sunscreens.

    Science.gov (United States)

    Benson, Heather Ae; Sarveiya, Vikram; Risk, Stacey; Roberts, Michael S

    2005-09-01

    Sunscreen products are widely used to protect the skin from sun-related damage. Previous studies have shown that some sunscreen chemicals are absorbed across the skin to the systemic circulation. The current study shows that absorption into the skin of sunscreen chemicals applied to the face is up to four times greater than that of the same product applied to the back. This has implications for the way sunscreen products are formulated and may allow the use of less potent products on the face compared with the rest of the body. The effect of formulation vehicles on the release and skin penetration of the common sunscreen agent benzophenone-3 (common name oxybenzone) was also assessed. Penetration of benzophenone-3 across excised human epidermis and high-density polyethylene (HDPE) membrane was measured using in vitro Franz-type diffusion cells. Penetration and epidermal retention was measured following application of infinite and finite (epidermis only) doses of benzophenone-3 in five vehicles: liquid paraffin, coconut oil, 50:50 ethanol:coconut oil, aqueous cream BP, and oily cream BP. Highest benzophenone-3 skin retention was observed for the ethanol:coconut oil combination. Maximal and minimal benzophenone-3 fluxes were observed from liquid paraffin and coconut oil, respectively. The alcohol-based vehicle exhibited low benzophenone-3 release from the vehicle but high skin penetration and retention.

  16. Influence of massage and occlusion on the ex vivo skin penetration of rigid liposomes and invasomes.

    Science.gov (United States)

    Trauer, Sindy; Richter, Heike; Kuntsche, Judith; Büttemeyer, Rolf; Liebsch, Manfred; Linscheid, Michael; Fahr, Alfred; Schäfer-Korting, Monika; Lademann, Jürgen; Patzelt, Alexa

    2014-02-01

    Liposomes are frequently described as drug delivery systems for dermal and transdermal applications. Recently, it has been shown that particulate substances penetrate effectively into hair follicles and that the follicular penetration depth can be increased by massaging the skin, which simulates the in vivo movement of hairs in the hair follicles. In the present study, massage was applied to skin mounted to Franz diffusion cells. By means of confocal laser scanning microscopy, the influence of massage and occlusion on the follicular penetration depths of rigid and flexible liposomes loaded with a hydrophilic and lipophilic dye was investigated. The application of massage increased follicular penetration significantly. Occlusion resulted in an increased follicular penetration depth only for rigid liposomes, whereas invasomes did not penetrate more effectively if occlusion was applied. The results confirm that massage is an important tool for increasing follicular penetration in ex vivo studies using Franz diffusion cells. Occlusion may reduce the efficacy of follicular penetration depending on the specific liposomal preparation. Rigidity in particular appears to be a relevant parameter.

  17. Penetration and decontamination of americium-241 ex vivo using fresh and frozen pig skin.

    Science.gov (United States)

    Tazrart, A; Bolzinger, M A; Moureau, A; Molina, T; Coudert, S; Angulo, J F; Briancon, S; Griffiths, N M

    2017-04-01

    Skin contamination is one of the most probable risks following major nuclear or radiological incidents. However, accidents involving skin contamination with radionuclides may occur in the nuclear industry, in research laboratories and in nuclear medicine departments. This work aims to measure the penetration of the radiological contaminant Americium ((241)Am) in fresh and frozen skin and to evaluate the distribution of the contamination in the skin. Decontamination tests were performed using water, Fuller's earth and diethylene triamine pentaacetic acid (DTPA), which is the recommended treatment in case of skin contamination with actinides such as plutonium or americium. To assess these parameters, we used the Franz cell diffusion system with full-thickness skin obtained from pigs' ears, representative of human skin. Solutions of (241)Am were deposited on the skin samples. The radioactivity content in each compartment and skin layers was measured after 24 h by liquid scintillation counting and alpha spectrophotometry. The Am cutaneous penetration to the receiver compartment is almost negligible in fresh and frozen skin. Multiple washings with water and DTPA recovered about 90% of the initial activity. The rest remains fixed mainly in the stratum corneum. Traces of activity were detected within the epidermis and dermis which is fixed and not accessible to the decontamination.

  18. [Assessment of ultraviolet radiation penetration into human skin. I. Theoretical analysis].

    Science.gov (United States)

    Cader, A; Jankowski, J

    1995-01-01

    This is one of the two articles under the same title "Assessment of ultraviolet radiation penetrating into human skin" which are aimed at presenting a part of broader studies in this area. They drive at identifying biophysical aspects of the effects of ultraviolet radiation on human skin. In order to characterise such parameters as UV reflectance from the skin surface of UV absorption and dispersion coefficients, it is necessary to develop appropriate methods. In Part I--"Theoretical analysis", theoretical principles for interpreting measurements of radiation dispersed in different geometrical configurations are presented. They can serve as a basis for estimating the values of UV linear absorption and dispersion coefficients in skin tissues.

  19. Alkylglycerol Derivatives, a New Class of Skin Penetration Modulators

    Directory of Open Access Journals (Sweden)

    Sergio Alberto Bernal-Chávez

    2017-01-01

    Full Text Available The absorption modulating activity of two alkylglycerol derivatives (batyl and chimyl alcohol on skin barrier properties was evaluated. Biophysical tests such as transepidermal water loss (TEWL and attenuated total reflectance–Fourier transform infrared (ATR-FTIR spectroscopy, as well as in vitro skin permeation studies, were performed in order to determine the effect of these compounds as chemical absorption modulators. Four drugs were used as models: three NSAIDS (diclofenac, naproxen, and piroxicam and glycyrrhizic acid. The results showed that treatment of the skin with alkylglycerols caused (i a reduction on the amount of drug permeated; (ii a reduction in TEWL; and (iii changes in the ATR-FTIR peaks of stratum corneum lipids, indicative of a more ordered structure. All of these findings confirm that alkyl glycerols have an absorption retarding effect on the drugs tested. Such effects are expected to give rise to important applications in the pharmaceutical and cosmetic sectors, in cases where it is desirable for the drug to remain in the superficial layers of the skin to achieve a local effect.

  20. Evaluation of moisture penetration through skin protectant barriers by paper chromatography.

    Science.gov (United States)

    Shah, S; Cornell, M; Ward, A J

    1995-01-01

    Currently, there is no convenient and safe experimental method in the literature to evaluate skin protectant formulations for barrier properties. A novel and simple experimental method, based on paper chromatography, was developed to screen a broad spectrum of skin protectants available for moisture penetration. The method involves the use of paper chromatography for determining the Moisture Penetration Rate through a thin barrier film of a given skin protectant product. It is simple, inexpensive, convenient, and safe and was used to evaluate 12 products currently used as skin protectants. This method can be used by formulators in their development efforts and by caregivers to determine the barrier properties of various products in a short period of time without expensive instrumentation or extensive time commitments. Skin irritation resulting from fecal and urinary incontinence is a common problem for geriatric patients (Fiers & Siebert, 1993, Talbot, 1994). Various products on the market today are used as protective barriers to prevent skin irritation from moisture penetration. However, from the caregiver's perspective, there is a need for identifying the best product or the relative ranking of products based on suitable test methods. There is a lack of suitable in vitro test methods to screen skin protectant barriers (Guillemin, Murset, Lob, & Riquez, 1974; Pigatto, Bigardi, Legori, Altomare, & Finzi, 1993) on the market. For any method to be acceptable it must be convenient, simple, reproducible, and safe for use on human volunteers. More importantly, it must have clinical relevance.

  1. In vitro study of ethosome penetration in human skin and hypertrophic scar tissue.

    Science.gov (United States)

    Zhang, Zhen; Wo, Yan; Zhang, Yixin; Wang, Danru; He, Rong; Chen, Huijin; Cui, Daxiang

    2012-08-01

    The purpose of this study is to characterize a novel transdermal delivery carrier, ethosomes containing 5-fluorouracil. The delivery of drugs from ethosomes in human hypertrophic scar (HS) and the mechanisms of action of ethosomes in human HS were investigated. Percutaneous ethosome permeation was evaluated in vitro in human HS and skin using a Franz's cell. The amount of 5-fluorouracil that permeated HS and skin after 24 hours was most abundant in ethosomes via HS (E-Scar), followed by hydroethanolic solution via HS (H-Scar), ethosomes via skin (E-Skin), and hydroethanolic solution via skin (H-Skin). The penetration of ethosomes in HS and skin was analyzed by ethosomes fluorescently labeled with rhodamine 6GO using confocal laser scanning microscopy. The fluorescence intensity after application for 24 hours was highest in E-Scar, followed by E-Skin, H-Scar, and H-Skin, which indicates the penetration of ethosomes in HS was greatest. In conclusion, we consider that ethosomes are a highly efficient carrier in HS.

  2. Release of Propolis Phenolic Acids from Semisolid Formulations and Their Penetration into the Human Skin In Vitro

    OpenAIRE

    2013-01-01

    Antioxidant and free radical scavenging effects are attributed to phenolic compounds present in propolis, and when delivered to the skin surface and following penetration into epidermis and dermis, they can contribute to skin protection from damaging action of free radicals that are formed under UV and premature skin aging. This study was designed to determine the penetration of phenolic acids and vanillin into the human skin in vitro from experimentally designed vehicles. Results of the stud...

  3. Tretinoin-based formulations - influence of concentration and vehicles on skin penetration

    Directory of Open Access Journals (Sweden)

    Edileia Bagatin

    2015-03-01

    Full Text Available Tretinoin is used in the management of acne and it is part of a gold standard treatment for photoaging. It has also been reported as an agent for superficial chemical peeling in highly concentrated formulations with few considerations about skin penetration. The aim of this study was to evaluate the influence of drug concentration and vehicles currently used on skin penetration of tretinoin. In vitro permeation tests were carried out using Franz diffusion cells fitted with porcine ear skin and 10% aqueous methanol in the receptor compartment. Formulations studied, cream or hydroalcoholic dispersion, containing 0.25%, 1% and 5% of tretinoin were placed in the donor compartment for six hours. Tretinoin concentration in skin layers was measured by high performance liquid chromatography. The largest amount of tretinoin from both vehicles was detected in stratum corneum with significant differences among the three concentrations. The hydroalcoholic dispersion was the best vehicle. Significant amounts of tretinoin were found even in deep layers of epidermis. The formulation with 0.25% tretinoin showed better results when considered the amount of tretinoin on skin in terms of percentage. Finally, skin penetration of tretinoin was influenced by vehicle and concentration of this drug used in formulation.

  4. Fiber optic microneedles for transdermal light delivery: ex vivo porcine skin penetration experiments.

    Science.gov (United States)

    Kosoglu, Mehmet A; Hood, Robert L; Chen, Ye; Xu, Yong; Rylander, Marissa Nichole; Rylander, Christopher G

    2010-09-01

    Shallow light penetration in tissue has been a technical barrier to the development of light-based methods for in vivo diagnosis and treatment of epithelial carcinomas. This problem can potentially be solved by utilizing minimally invasive probes to deliver light directly to target areas. To develop this solution, fiber optic microneedles capable of delivering light for either imaging or therapy were manufactured by tapering step-index silica-based optical fibers employing a melt-drawing process. Some of the microneedles were manufactured to have sharper tips by changing the heat source during the melt-drawing process. All of the microneedles were individually inserted into ex vivo pig skin samples to demonstrate the feasibility of their application in human tissues. The force on each microneedle was measured during insertion in order to determine the effects of sharper tips on the peak force and the steadiness of the increase in force. Skin penetration experiments showed that sharp fiber optic microneedles that are 3 mm long penetrate through 2 mm of ex vivo pig skin specimens. These sharp microneedles had a minimum average diameter of 73 mum and a maximum tip diameter of 8 mum. Flat microneedles, which had larger tip diameters, required a minimum average diameter of 125 mum in order to penetrate through pig skin samples. Force versus displacement plots showed that a sharp tip on a fiber optic microneedle decreased the skin's resistance during insertion. Also, the force acting on a sharp microneedle increased more steadily compared with a microneedle with a flat tip. However, many of the sharp microneedles sustained damage during skin penetration. Two designs that did not accrue damage were identified and will provide a basis of more robust microneedles. Developing resilient microneedles with smaller diameters will lead to transformative, novel modes of transdermal imaging and treatment that are less invasive and less painful for the patient.

  5. DA 5505: a novel topical formulation of terbinafine that enhances skin penetration and retention.

    Science.gov (United States)

    Thapa, Raj Kumar; Han, Sang-Duk; Park, Hyoung Geun; Son, Miwon; Jun, Joon Ho; Kim, Jong Oh

    2015-01-01

    Topical fungal infections can become severe if left untreated. Efficient treatment modalities for topical fungal infections aid the penetration of antifungal agents deep into viable skin layers. Terbinafine is a fungicidal agent that inhibits ergosterol, an essential fungal component. The main objective of this study was to evaluate skin permeation and retention of a terbinafine-loaded solution containing chitosan as a film former. Comparative assessment of skin permeation and retention was performed using a prepared formulation (DA 5505) and marketed formulations of terbinafine in murine and porcine skin. To mimic fungal infection of skin, keratinized skin was induced in NC/Nga mice. In comparison with the marketed formulations, DA 5505 exhibited significantly better skin permeation. The flux, permeation coefficient, and enhancement ratio of terbinafine were remarkably increased by DA 5505 in comparison with the marketed formulations, and lag time was dramatically reduced. DA 5505 significantly increased cumulative terbinafine retention in viable skin layers in comparison with the marketed solution, suggesting enhanced efficacy. Furthermore, DA 5505 exhibited superior skin permeation in normal skin and keratinized skin. Thus, the DA 5505 formulation has the potential to effectively deliver terbinafine to superficial and deep cutaneous fungal infections.

  6. Skin penetration behaviour of liposomes as a function of their composition.

    Science.gov (United States)

    Gillet, A; Lecomte, F; Hubert, P; Ducat, E; Evrard, B; Piel, G

    2011-09-01

    Deformable liposomes have been developed and evaluated as a novel topical and transdermal delivery system. Their mechanism of drug transport into and through the skin has been investigated but remains a much debated question. The present study concerns ex vivo diffusion experiments using pig ear skin in order to explain the penetration mechanism of classical and deformable liposomes. Classical and deformable vesicles containing betamethasone in the aqueous compartment through the use of cyclodextrin inclusion complexes were compared to vesicles encapsulating betamethasone in their lipid bilayer. Deformable liposomes contained sodium deoxycholate as the edge activator. Liposomes were characterised by their diameter, encapsulation efficiency, deformability, stability (in terms of change in diameter) and release of encapsulated drug. Ex vivo diffusion studies using Franz diffusion cells were performed. Confocal microscopy was performed to visualise the penetration of fluorescently labelled liposomes into the skin. This study showed that liposomes do not stay intact when they penetrate the deepest layers of the skin. Betamethasone is released from the vesicles after which free drug molecules can diffuse through the stratum corneum and partition into the viable skin tissue.

  7. Development and validation of HPLC method for imiquimod determination in skin penetration studies.

    Science.gov (United States)

    De Paula, Daniel; Martins, Carolina Azenha; Bentley, Maria Vitória Lopes Badra

    2008-12-01

    A simple, rapid and sensitive analytical procedure for the measurement of imiquimod in skin samples after in vitro penetration studies has been developed and validated. In vitro penetration studies were carried out in Franz diffusion cells with porcine skin. Tape stripping technique was used to separate the stratum corneum (SC) from the viable epidermis and dermis. Imiquimod was extracted from skin samples using a 7:3 (v/v) methanol:acetate buffer (100 mM, pH 4.0) solution and ultrasonication. Imiquimod was analyzed by HPLC using C(8) column and UV detection at 242 nm. The mobile phase used was acetonitrile:acetate buffer (pH 4.0, 100 mM):diethylamine (30:69.85:0.15, v/v) with flow rate 1 mL/min. Imiquimod eluted at 4.1 min and the running time was limited to 6.0 min. The procedure was linear across the following concentration ranges: 100-2500 ng/mL for both SC and tape-stripped skin and 20-800 ng/mL for receptor solution. Intra-day and inter-day accuracy and precision values were lower than 20% at the limit of quantitation. The recovery values ranged from 80 to 100%. The method is adequate to assay imiquimod from skin samples, enabling the determination of the cutaneous penetration profile of imiquimod by in vitro studies.

  8. Spatially Resolved Two-Color Diffusion Measurements in Human Skin Applied to Transdermal Liposome Penetration

    DEFF Research Database (Denmark)

    Brewer, Jonathan; Bloksgaard, Maria; Kubiak, Jakub

    2013-01-01

    A multiphoton excitation-based fluorescence fluctuation spectroscopy method, Raster image correlation spectroscopy (RICS), was used to measure the local diffusion coefficients of distinct model fluorescent substances in excised human skin. In combination with structural information obtained...... of the liposome composition (phospholipids or transfersomes), our results show a clear lack of cross-correlation below the skin surface, indicating that the penetration of intact liposomes is highly compromised by the skin barrier.Journal of Investigative Dermatology advance online publication, 6 December 2012...... is very heterogeneous on a microscopic scale. This diffusion-based strategy was further exploited to investigate the integrity of liposomes during transdermal penetration. Specifically, the diffusion of dual-color fluorescently labeled liposomes-containing an amphiphilic fluorophore in the lipid bilayer...

  9. Simultaneous analysis of skin penetration of surfactant and active drug from fluorosurfactant-based microemulsions.

    Science.gov (United States)

    Mahrhauser, Denise; Hoppel, Magdalena; Schöll, Judith; Binder, Lisa; Kählig, Hanspeter; Valenta, Claudia

    2014-09-01

    The purpose of this study was to investigate the penetrated amount of the incorporated model drug diclofenac-sodium and of a fluorosurfactant as specific vehicle constituent of topically applied microemulsions at the same time. To this end, the penetration depth of each compound was elucidated through tape stripping studies by the simultaneous quantification of diclofenac-sodium and the fluorosurfactant from the same sample. A new approach was made by using the very sensitive and specific (19)F NMR (nuclear magnetic resonance) for quantification of the fluorinated vehicle component. The tape stripping experiments with the microemulsions showed an almost similar penetration velocity of diclofenac-sodium and fluorosurfactant, suggesting that the surfactant within the microemulsion-structure intensified the stratum corneum uptake of the incorporated active constituent. Moreover, ATR-FTIR studies on porcine ear skin revealed significant shifts of the CH₂ stretching absorbances, which are associated with an enhanced disorder of the SC lipids resulting in a decreased skin barrier function, after application of the microemulsions. However, the application of pure fluorosurfactant did not cause any shifts in the CH₂ stretching absorbances. It can be thereby concluded that the prepared microemulsions exerted specific effects on skin integrity resulting in a "push" of diclofenac-sodium penetration.

  10. Photoacoustic evaluation of the penetration of piroxicam gel applied with phonophoresis into human skin

    Energy Technology Data Exchange (ETDEWEB)

    Silveira, F L F D; Barja, P R [Research and Development Institute, UNIVAP, Av. Shishima Hifumi 2911, Sao Jose dos Campos, SP, 12209-010 (Brazil); Acosta-Avalos, D, E-mail: barja@univap.b [Centro Brasileiro de Pesquisas Fisicas (CBPF), R.Xavier Sigaud 150, Rio de Janeiro, RJ, 22290-180 (Brazil)

    2010-03-01

    The photoacoustic (PA) technique has been increasingly employed in biomedical studies, allowing in vivo skin measurements not easily performed with other techniques. It is possible to use PA measurements to evaluate transdermal delivery of products topically applied through manual massage or phonophoresis, that is the utilization of ultrasound waves to enhance drug absorption. The aim of this study was to analyze the influence of the period of phonophoresis application in the transdermal penetration of piroxicam gel. In vivo PA measurements employed a tungsten lamp as light source and a thin aluminum foil closing the PA chamber. The PA signals of the arm (i) clean; and (ii) after phonophoresis were utilized to estimate the concentration of piroxicam into skin. For all (4) volunteers, drug concentration in skin after phonophoresis application was the same for the different application times employed; in this way, phonophoresis for one minute seemed to be sufficient to enhance piroxicam penetration into skin. The actual amount of drug delivered into tissue depends on the person, suggesting a dependency with the skin type, which affects the PA signal level [2]. We conclude that drug delivery depends not only on the application method, but also on the specific skin type.

  11. Is skin penetration a determining factor in skin sensitization potential and potency? Refuting the notion of a LogKow threshold for Skin Sensitization

    Science.gov (United States)

    Summary:Background. It is widely accepted that substances that cannot penetrate through the skin will not be sensitisers. Thresholds based on relevant physicochemical parameters such as a LogKow > 1 and a MW < 500, are assumed and widely accepted as self-evident truths. Objective...

  12. Is skin penetration a determining factor in skin sensitization potential and potency? Refuting the notion of a LogKow threshold for Skin Sensitization

    Science.gov (United States)

    Summary:Background. It is widely accepted that substances that cannot penetrate through the skin will not be sensitisers. Thresholds based on relevant physicochemical parameters such as a LogKow > 1 and a MW < 500, are assumed and widely accepted as self-evident truths. Objective...

  13. A study considering the force required for broken glass bottles to penetrate a skin simulant.

    Science.gov (United States)

    Nolan, Gary; Lawes, Simon; Hainsworth, Sarah; Rutty, Guy

    2012-01-01

    Injuries and assaults related to alcohol consumption are a growing concern in many countries. In such cases, the use of impulsive weapons, an object from the immediate environment, such as a glass bottle, is not uncommon. This current study utilises a material testing system to measure the force required to push a broken glass bottle into a skin simulant with the displacement of the bottle into the skin simulant being recorded simultaneously, using a linear variable differential transformer (LVDT). From this data, load versus displacement plots were produced. Multi-detector computed tomography (MDCT) was also used to analyse bottle wall thickness to determine if a relationship could be found between force required for penetration and bottle wall thickness. The forces required for the penetration of the skin simulant ranged from 9.8 to 56.7 N. The range was found to be independent of bottle type with the variation in force for penetration being attributed to the varying fracture points, with some fractures presenting a sharper point on first contact with the skin. Although the dangers associated with the use of broken bottles as weapons is apparent, there is a paucity of information in this area in the current English literature, which this study has addressed. The results of this study also highlight the risks of attempting reconstructions of broken bottle stab events.

  14. Absorption spectra and light penetration depth of normal and pathologically altered human skin

    Science.gov (United States)

    Barun, V. V.; Ivanov, A. P.; Volotovskaya, A. V.; Ulashchik, V. S.

    2007-05-01

    A three-layered skin model (stratum corneum, epidermis, and dermis) and engineering formulas for radiative transfer theory are used to study absorption spectra and light penetration depths of normal and pathologically altered skin. The formulas include small-angle and asymptotic approximations and a layer-addition method. These characteristics are calculated for wavelengths used for low-intensity laser therapy. We examined several pathologies such as vitiligo, edema, erythematosus lupus, and subcutaneous wound, for which the bulk concentrations of melanin and blood vessels or tissue structure (for subcutaneous wound) change compared with normal skin. The penetration depth spectrum is very similar to the inverted blood absorption spectrum. In other words, the depth is minimal at blood absorption maxima. The calculated absorption spectra enable the power and irradiation wavelength providing the required light effect to be selected. Relationships between the penetration depth and the diffuse reflectance coefficient of skin (unambiguously expressed through the absorption coefficient) are analyzed at different wavelengths. This makes it possible to find relationships between the light fields inside and outside the tissue.

  15. Depth of penetration of an 850nm wavelength low level laser in human skin.

    Science.gov (United States)

    Esnouf, Alan; Wright, Philip A; Moore, Joan C; Ahmed, Salim

    2007-01-01

    Low Level Laser Therapy is used for a wide variety of conditions including superficial skin sores, musculoskeletal and joint problems, and dentistry. Knowledge of the penetration depth of laser radiation in human skin is an essential prerequisite to identifying its method of action. Mathematical simulations and estimates from the literature suggest that the depth of penetration of laser radiation using wavelengths from 630nm up to 1100nm may be up to 50mm. The aim of this study is to directly measure the penetration depth of a Low Level Laser in human tissue. Human abdominal skin samples up to 0.784mm thickness were harvested by dermatome following abdominoplasty procedures. These samples were irradiated by a Gallium Aluminium Arsenide Laser (Wavelength 850nm near infra-red invisible light, 100mW, 24kHz, 0.28mm diameter probe) and the transmitted radiation measured with an Ophir Optronics 'Nova' external energy meter. The intensity of laser radiation reduced by 66% after being transmitted through a 0.784mm sample of human abdominal tissue. In this study most laser radiation was absorbed within the first 1mm of skin.

  16. Determination of three ultraviolet filters in sunscreen formulations and from skin penetration studies by high-performance liquid chromatography

    Directory of Open Access Journals (Sweden)

    Fernanda Maria Pinto Vilela

    2011-01-01

    Full Text Available An analytical procedure to quantify 3-benzophenone, octylmethoxycinnamate and octylsalicylate was validated and employed to assess these ultraviolet filters in sunscreen formulations and from skin penetration studies. The effect of the vehicle on the skin retention of these filters was investigated. HPLC and extraction procedure were found to be reliable when obtaining data for the sunscreen formulations and for evaluation skin penetration. The results demonstrated that a cream gel generated higher epidermal concentrations of these filters than a lotion or cream-based formulation. Additionally, when comparing the skin retentions of each filter using the same formulation, 3-benzophenone showed the highest skin retention.

  17. Percutaneous penetration of uranium in rats after a contamination on intact or wounded skin

    Energy Technology Data Exchange (ETDEWEB)

    Petitot, F.; Gautier, C.; Moreels, A.M.; Frelon, S.; Paquet, F. [Institut de Radioprotection et de Surete Nucleaire, Laboratoire de Radiotoxicologie Experimentale, IRSN/DRPH/SRBE/LRTOX, Site du Tricastin, B.P. 166, 26702 Pierrelatte Cedex (France)

    2007-07-01

    The aim of this work is to assess in vivo in a hairless rat model, the percutaneous diffusion of uranium through intact or wounded rat skin. Six types of wounds were simulated by excoriation and burns with 10 N HF, 2, 5 and 14 N HNO{sub 3} and 10 N NaOH on anesthetized hairless rats. Percutaneous penetration through wounded skin towards blood and subsequent urinary excretion of uranium was followed in vivo during 24 h. The influence of the physicochemical form (solution or powder) of uranyl nitrate (UN) on its percutaneous diffusion was also investigated. UN, even as a powder, can diffuse through intact skin. The presence of uranium in blood is more persistent and its urinary elimination is slower after an HF burn than after an HNO{sub 3} burn. Excoriation increases dramatically percutaneous absorption of UN. Thus, percutaneous diffusion of UN is largely dependent on skin barrier integrity with a particular importance of stratum corneum. (authors)

  18. Penetration and growth of DPPC/DHPC bicelles inside the stratum corneum of the skin.

    Science.gov (United States)

    Barbosa-Barros, L; de la Maza, A; Estelrich, J; Linares, A M; Feliz, M; Walther, P; Pons, R; López, O

    2008-06-03

    The effect of dipalmitoyl phosphatidylcholine (DPPC)/dihexanoyl phosphatidylcholine (DHPC) bicelles on the microstructure of pig stratum corneum (SC) in vitro was evaluated. The physicochemical characterization of these nanoaggregates revealed small disks with diameters around 15 nm and a thickness of 5.4 nm. Upon dilution, the bicelles grow and transform into vesicles. Cryogenic scanning electron microscopy (cryo-SEM) images of the SC pieces treated with this system showed vesicles of about 200 nm and lamellar-like structures in the intercellular lipid areas. These vesicles probably resulted from the growth and molecular rearrangement of the DPPC/DHPC bicelles after penetrating the SC. The presence of lamellar-like structures is ascribed to the interaction of the lipids from bicelles with the SC lipids. The bicellar system used is suitable to penetrate the skin SC and to reinforce the intercellular lipid areas, constituting a promising tool for skin applications.

  19. In vivo evaluation of the penetration of topically applied drugs into human skin by spectroscopic methods.

    Science.gov (United States)

    Sennhenn, B; Giese, K; Plamann, K; Harendt, N; Kölmel, K

    1993-01-01

    Spectroscopic techniques are reported on which allow to study in vivo the penetration behaviour of topically applied light-absorbing drugs into human skin. Remittance spectroscopy, a purely optical method, provides a good tool in both, skin adaptation by use of a remote viewing head coupled to the spectrometer via optical fibres, and adequate sensitivity for the detection of small amounts of the applied drugs. The measuring depth in the skin is determined by the wavelength-dependent optical penetration depth, which itself depends on light absorption and light scattering. In the UV-spectral region the optical penetration depth is of the order of the thickness of the stratum corneum (UV-A) or of only a superficial part of it (UV-B, UV-C). Fluorescence spectroscopy, another optical method, offers two kinds of drug detection, a direct one in case of self-fluorescent drugs or an indirect one being based on the light absorption of the drug, which may give rise to a screening of the self-fluorescence of the skin itself or of an applied marker. The measuring depth is comparable to that achieved with remittance spectroscopy. A third method is photothermal spectroscopy which is determined by thermal properties of the skin in addition to optical properties. Photothermal spectroscopy is unique in that it allows depth profiles of drug concentration to be measured non-invasively, as the photothermal measuring depth can be changed by varying the modulation frequency of the intensity-modulated incident light. Results of measurements demonstrating the potentials of these spectroscopic methods are presented.

  20. Interactions of skin thickness and physicochemical properties of test compounds in percutaneous penetration studies

    DEFF Research Database (Denmark)

    Wilkinson, Simon C.; Maas, Wilfred J. M.; Nielsen, Jesper Bo

    2006-01-01

    conditions was measured using flow through cells for 8-24 h. Saline (adjusted to pH 7.4) was used as receptor fluid, with BSA added for studies with testosterone and propoxur. Following exposure, the remaining surface dose was removed by swabbing and the skin digested prior to scintillation counting. Results......Abstract   Objectives: To determine the effect of skin thickness on the percutaneous penetration and distribution of test compounds with varying physicochemical properties using in vitro systems. Studies were carried out in accordance with OECD guidelines on skin absorption tests. Methods......: Percutaneous penetration of caffeine (log P -0.01), testosterone (log P 3.32), propoxur (log P 1.52) (finite dose in ethanol to water vehicle ratio) and butoxyethanol (log P 0.83) (undiluted finite dose or as an infinite dose 50% [v/v] aqueous solution) through skin of varying thicknesses under occluded...

  1. Interactions of skin thickness and physicochemical properties of test compounds in percutaneous penetration studies

    DEFF Research Database (Denmark)

    Wilkinson, Simon C.; Maas, Wilfred J. M.; Nielsen, Jesper Bo

    2006-01-01

    Abstract   Objectives: To determine the effect of skin thickness on the percutaneous penetration and distribution of test compounds with varying physicochemical properties using in vitro systems. Studies were carried out in accordance with OECD guidelines on skin absorption tests. Methods......: Percutaneous penetration of caffeine (log P -0.01), testosterone (log P 3.32), propoxur (log P 1.52) (finite dose in ethanol to water vehicle ratio) and butoxyethanol (log P 0.83) (undiluted finite dose or as an infinite dose 50% [v/v] aqueous solution) through skin of varying thicknesses under occluded...... conditions was measured using flow through cells for 8-24 h. Saline (adjusted to pH 7.4) was used as receptor fluid, with BSA added for studies with testosterone and propoxur. Following exposure, the remaining surface dose was removed by swabbing and the skin digested prior to scintillation counting. Results...

  2. De Novo Design of Skin-Penetrating Peptides for Enhanced Transdermal Delivery of Peptide Drugs.

    Science.gov (United States)

    Menegatti, Stefano; Zakrewsky, Michael; Kumar, Sunny; De Oliveira, Joshua Sanchez; Muraski, John A; Mitragotri, Samir

    2016-03-09

    Skin-penetrating peptides (SPPs) are attracting increasing attention as a non-invasive strategy for transdermal delivery of therapeutics. The identification of SPP sequences, however, currently performed by experimental screening of peptide libraries, is very laborious. Recent studies have shown that, to be effective enhancers, SPPs must possess affinity for both skin keratin and the drug of interest. We therefore developed a computational process for generating and screening virtual libraries of disulfide-cyclic peptides against keratin and cyclosporine A (CsA) to identify SPPs capable of enhancing transdermal CsA delivery. The selected sequences were experimentally tested and found to bind both CsA and keratin, as determined by mass spectrometry and affinity chromatography, and enhance transdermal permeation of CsA. Four heptameric sequences that emerged as leading candidates (ACSATLQHSCG, ACSLTVNWNCG, ACTSTGRNACG, and ACSASTNHNCG) were tested and yielded CsA permeation on par with previously identified SPP SPACE (TM) . An octameric peptide (ACNAHQARSTCG) yielded significantly higher delivery of CsA compared to heptameric SPPs. The safety profile of the selected sequences was also validated by incubation with skin keratinocytes. This method thus represents an effective procedure for the de novo design of skin-penetrating peptides for the delivery of desired therapeutic or cosmetic agents.

  3. Glove material, reservoir formation, and dose affect glove permeation and subsequent skin penetration.

    Science.gov (United States)

    Nielsen, Jesper Bo; Sørensen, Jens Ahm

    2012-02-15

    Protective gloves are used to reduce dermal exposure when managing chemical exposures at the work place. Different glove materials may offer different degrees of protection. The present study combined the traditional ASTM (American Society for Testing and Materials) model with the Franz diffusion cell to evaluate overall penetration through glove and skin as well as the deposition in the different reservoirs. Benzoic acid was applied on latex or nitrile gloves placed on top of human skin. The amounts of chemical were quantified in the glove material, between glove and skin, within the skin, and in the receptor chamber. Both glove materials reduce total penetration of benzoic acid, but nitrile gloves offer a significantly better protection than latex gloves. This difference was less pronounced at the higher of the two concentrations of benzoic acid applied. Thus, glove types that offer relevant protection at low concentrations does not necessarily give appropriate protection at high concentrations. Significant amounts of benzoic acid could be extracted from the glove materials after exposure. If a chemical is accumulated in the glove material, reuse of single-use gloves should be cautioned. The reuse of gloves is generally not to be recommended without effective decontamination.

  4. Human Skin Penetration of Cobalt Nanoparticles Through Intact and Damaged Skin

    OpenAIRE

    LARESE FILON Francesca; Crosera, Matteo; TIMEUS Elena; Adami, Gianpiero; Bovenzi, Massimo; Ponti, Jessica; Maina, Giovanni

    2011-01-01

    Cobalt nanoparticles (CoNPs) are produced for many applications but there is a lack of data on human absorption. The aim of our study was to evaluate the CoNPs skin absorption. Experiments were performed using Franz cells with human skin. Physiological solution was used as receiving phase and 1.0 mg cm-2 of CoNPs was applied as donor phase for 24 h. Mean Co content of 8.3 ± 1.5 ng cm-2 and 1.87 ± 0.86 ug cm-2 were found in the receiving solutions of cells where the CoNPs suspension was app...

  5. [A new ECG electrode concept for the conduction of fetal heart action potentials without penetration of the skin].

    Science.gov (United States)

    Schmidt, S; Langner, K; Rothe, J; Saling, E

    1982-10-01

    Internal cardiotocography is an important method for reliable supervision of the fetus during labor. The main task is the prevention of fetal hypoxia. However, there is a considerable disadvantage as the electrodes used penetrate the fetal skin, creating a possible entry point for organisms. The concept we have developed forms a new way of decreasing the risk of infection during labor by conducting the fetal heart rate potentials without penetrating the skin. The electrode is fixed to the skin of the presenting part by tissue adhesive and electrical contact between the fetal skin and the wire of the electrode is established through using electrolyte fluid.

  6. Penetration of tamoxifen citrate loaded ethosomes and liposomes across human skin: a comparative study with confocal laser scanning microscopy.

    Science.gov (United States)

    Sarwa, Khomendra K; Suresh, Preeti K; Rudrapal, Mithun; Verma, Vinod K

    2014-01-01

    In the present study, ethosomal and liposomal formulations containing tamoxifen citrate were prepared and evaluated for their penetration properties in human cadaver skin using Franz diffusion cell and confocal laser scanning microscope (CLSM). The results clearly revealed that ethosomal vesicles showed a better drug permeation profile than that of liposomal vesicles. In addition, low fluorescence intensity in CLSM was recorded with liposomes as compared to ethosomes, indicating lower cumulative amount of drug permeation from liposomal vesicles. Furthermore, CLSM showed uniform fluorescence intensity across the entire depth of skin in ethosomal treatment, indicating high penetrability of ethosomal vesicles through human cadaver skin. In contrast, low penetrability of conventional liposomal vesicles was recorded as penetration was limited to the 7(th) section (i.e. upper epidermis layer) of skin as evident from visualization of intact liposomal vesicles in CLSM.

  7. Assessment of penetration of quantum dots through in vitro and in vivo human skin using the human skin equivalent model and the tape stripping method

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Sang Hoon; Kim, Jae Hwan; Yi, Sang Min [Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology and Division of Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul (Korea, Republic of); Lee, Jung Pyo; Kim, Jin Ho; Sohn, Kyung Hee; Park, Kui Lea [National Institute of Toxicological Research, Seoul (Korea, Republic of); Kim, Meyoung-Kon [Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of); Son, Sang Wook, E-mail: skin4u@korea.ac.kr [Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology and Division of Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul (Korea, Republic of)

    2010-04-09

    Quantum dots (QDs) are rapidly emerging as an important class of nanoparticles (NPs) with potential applications in medicine. However, little is known about penetration of QDs through human skin. This study investigated skin penetration of QDs in both in vivo and in vitro human skin. Using the tape stripping method, this study demonstrates for the first time that QDs can actually penetrate through the stratum corneum (SC) of human skin. Transmission electron microscope (TEM) and energy diverse X-ray (EDX) analysis showed accumulation of QDs in the SC of a human skin equivalent model (HSEM) after dermal exposure to QDs. These findings suggest possible transdermal absorption of QDs after dermal exposure over a relatively long period of time.

  8. Ex vivo skin permeation and penetration of nonivamide from and in vivo skin tolerability of film-forming formulations containing porous silica.

    Science.gov (United States)

    Heck, Rouven; Lukić, Milica Ž; Savić, Snežana D; Daniels, Rolf; Lunter, Dominique J

    2017-08-30

    The purpose of this study was to evaluate skin permeation and penetration of nonivamide which has been formulated in novel film-forming formulations (FFFs). These formulations aim to prolong the availability of capsaicinoids which are used in long-term treatment of chronic pruritus. An oily solution of nonivamide was loaded into porous silica particles which then were suspended in an aqueous dispersion of a sustained release polymer. Permeation and penetration experiments were performed ex vivo with postauricular porcine skin using modified Franz diffusion cells. The penetrated drug amount was assessed ex vivo by skin surface biopsy followed by cryo-sectioning. Furthermore, in vivo skin irritation experiments were performed to compare the potential skin irritation caused by the FFFs to conventionally used semi-solid formulations. Permeation rates of nonivamide from FFF through the skin are comparable to that from clinically used immediate release formulations. This elucidates the therapeutic safety profile of the novel FFF. Penetration studies confirmed the prolonged drug availability at the site of action. FFFs were found not to irritate the skin of healthy volunteers. FFFs with sustained nonivamide penetration represent safe and easy-to-use formulations. They therefore may improve the treatment of chronic pruritus with capsaicinoids by enhancing patient compliance through a sustained release regime. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Release of Propolis Phenolic Acids from Semisolid Formulations and Their Penetration into the Human Skin In Vitro

    Directory of Open Access Journals (Sweden)

    Modestas Žilius

    2013-01-01

    Full Text Available Antioxidant and free radical scavenging effects are attributed to phenolic compounds present in propolis, and when delivered to the skin surface and following penetration into epidermis and dermis, they can contribute to skin protection from damaging action of free radicals that are formed under UV and premature skin aging. This study was designed to determine the penetration of phenolic acids and vanillin into the human skin in vitro from experimentally designed vehicles. Results of the study demonstrated the ability of propolis phenolic acids (vanillic, coumaric, caffeic, and ferulic acids and vanillin to penetrate into skin epidermis and dermis. The rate of penetration and distribution is affected both by physicochemical characteristics of active substances and physical structure and chemical composition of semisolid vehicle. Vanillin and vanillic acid demonstrated relatively high penetration through epidermis into dermis where these compounds were concentrated, coumaric and ferulic acids were uniformly distributed between epidermis and dermis, and caffeic acid slowly penetrated into epidermis and was not determined in dermis. Further studies are deemed relevant for the development of semisolid topically applied systems designed for efficient delivery of propolis antioxidants into the skin.

  10. A Method for Quantification of Penetration of Nanoparticles through Skin Layers Using Near-Infrared Optical Imaging

    Directory of Open Access Journals (Sweden)

    Melinda Stees

    2015-07-01

    Full Text Available Our study presents a new method for tracking nanoparticle penetration through different layers of the skin using near-infrared dye-loaded nanoparticles (hydrodynamic diameter = 156 nm and optical imaging. The dye-loaded nanoparticles were mixed in a topical skin cream, applied to human cadaver skin and incubated either for three or 24 h post-application, skin tissue was clipped between glass slides prior to imaging for signal intensity across the skin thickness using an optical imaging system. The data show that nanoparticles penetrate through all the layers of the skin but there is almost an exponential decay in the signal intensity from epidermis to dermis. Depending upon the incubation time, about 55%–59% of the total signal was seen in the epidermis and the remaining through dermis and hypodermis. The advantage of the method is that it allows quantitative analysis of the extent of penetration of nanoparticles through different layers of the skin without interference of any background signal from skin tissue, and without requiring extensive tissue processing. Our method could potentially be used to study the effect of nanoparticle properties and/or the use of different formulation additives on penetration of nanoparticles through different skin layers.

  11. Spatially resolved two-color diffusion measurements in human skin applied to transdermal liposome penetration.

    Science.gov (United States)

    Brewer, Jonathan; Bloksgaard, Maria; Kubiak, Jakub; Sørensen, Jens Ahm; Bagatolli, Luis A

    2013-05-01

    A multiphoton excitation-based fluorescence fluctuation spectroscopy method, Raster image correlation spectroscopy (RICS), was used to measure the local diffusion coefficients of distinct model fluorescent substances in excised human skin. In combination with structural information obtained by multiphoton excitation fluorescence microscopy imaging, the acquired diffusion information was processed to construct spatially resolved diffusion maps at different depths of the stratum corneum (SC). Experiments using amphiphilic and hydrophilic fluorescently labeled molecules show that their diffusion in SC is very heterogeneous on a microscopic scale. This diffusion-based strategy was further exploited to investigate the integrity of liposomes during transdermal penetration. Specifically, the diffusion of dual-color fluorescently labeled liposomes--containing an amphiphilic fluorophore in the lipid bilayer and a hydrophilic fluorophore encapsulated in the liposome lumen--was measured using cross-correlation RICS. This type of experiment allows discrimination between separate (uncorrelated) and joint (correlated) diffusion of the two different fluorescent probes, giving information about liposome integrity. Independent of the liposome composition (phospholipids or transfersomes), our results show a clear lack of cross-correlation below the skin surface, indicating that the penetration of intact liposomes is highly compromised by the skin barrier.

  12. Formulation development of transdermal dosage forms: quantitative structure-activity relationship model for predicting activities of terpenes that enhance drug penetration through human skin.

    Science.gov (United States)

    Kang, L; Yap, C W; Lim, P F C; Chen, Y Z; Ho, P C; Chan, Y W; Wong, G P; Chan, S Y

    2007-07-31

    Terpenes and terpenoids have been used as enhancers in transdermal formulations for facilitating penetration of drugs into human skin. Knowledge of the correlation between the human skin penetration effect (HSPE) and the physicochemical properties of these enhancers is important for facilitating the discovery and development of more enhancers. In this work, the HSPE of 49 terpenes and terpenoids were compared by the in vitro permeability coefficients of haloperidol (HP) through excised human skin. A first-order multiple linear regression (MLR) model was constructed to link the permeability coefficient of the drug to the lipophilicity, molecular weight, boiling point, the terpene type and the functional group of each enhancer. The Quantitative Structure-Activity Relationship (QSAR) model was derived from our data generated by using standardized experimental protocols, which include: HP in propylene glycol (PG) of 3 mg/ml as the donor solution containing 5% (w/v) of the respective terpene, the same composition and volume of receptor solution, similar human skin samples, in the same set of automated flow-through diffusion cells. The model provided a simple method to predict the enhancing effects of terpenes for drugs with physicochemical properties similar to HP. Our study suggested that an ideal terpene enhancer should possess at least one or combinations of the following properties: hydrophobic, in liquid form at room temperature, with an ester or aldehyde but not acid functional group, and is neither a triterpene nor tetraterpene. Possible mechanisms revealed by the QSAR model were discussed.

  13. Penetration power of antiseptic creams ("in vitro" model with pig skin).

    Science.gov (United States)

    Garcia Torres, V; Herruzo, R; Santos Heredero, F X; Lenguas, F; Martinez Ratero, S; del Fresno, C

    1991-01-01

    By means of an "in vitro" method using pig skin, the authors determine the penetration power of some antiseptic creams in order out the most effective one from this point of view in the treatment of subscar-located infections. The following antiseptic creams were studied: 1% Silver Sulfadiazine, 1% Silver Sulfadiazine with 2.2% Cerium Nitrate, 2.2% Cerium Nitrate, 10% Iodine Povidone, 0.2% Nitrofurazone 0.1%, 0.5% and 1% Chlorhexidine. These products were faced with 17 microorganisms isolated from burn wounds and a control one. The minimal inhibitory concentrations (MIC) obtained after passing through the penetration power of some antiseptic creams in order to find out the most effective one from this point of view in the treatment of subscar-located infections.

  14. Impact of semi-solid formulations on skin penetration of iron oxide nanoparticles

    OpenAIRE

    Musazzi, Umberto M.; Santini, Benedetta; Selmin, Francesca; Marini, Valentina; Corsi, Fabio; Allevi, Raffaele; Ferretti, Anna M.; Prosperi, Davide; Cilurzo, Francesco; Colombo, Miriam; Minghetti, Paola

    2017-01-01

    Background This work aimed to provide useful information on the incidence of the choice of formulation in semi-solid preparations of iron-oxide nanoparticles (IONs). The appropriate analytical methods to assess the IONs physical stability and the effect of the semi-solid preparations on IONs human skin penetration were discussed. The physical stability of IONs (Dh = 31 ± 4 nm; ζ = −65 ± 5 mV) loaded in five semi-solid preparations (0.3% w/v), namely Carbopol gel (CP), hydroxyethyl cellulose g...

  15. Skin Needling to Enhance Depigmenting Serum Penetration in the Treatment of Melasma

    Science.gov (United States)

    Fabbrocini, G.; De Vita, V.; Fardella, N.; Pastore, F.; Annunziata, M. C.; Mauriello, M. C.; Monfrecola, A.; Cameli, N.

    2011-01-01

    Melasma is a common hypermelanotic disorder affecting the facial area which has a considerable psychological impact on the patient. Managing melasma is a difficult challenge that requires long-term treatment with a number of topical agents, such as rucinol and sophora-alpha. Aims. We aim to compare the combined treatment of skin needling and depigmenting serum with that using depigmenting serum alone in the treatment of melasma, in order to evaluate the use of microneedles as a means to enhance the drug's transdermal penetration. Methods. Twenty patients were treated with combined skin needling and depigmenting serum on one side of the face and with depigmenting serum alone on the other side. The outcome was evaluated periodically for up to two months using the Melasma Area Severity Index score and the Spectrocolorimeter X-Rite 968. Results. The side with combined treatment (skin needling + depigmenting serum) presented a statistically significant reduction in MASI score and luminosity index (L) levels compared to the side treated with depigmenting serum alone, and clinical symptoms were significantly improved. Conclusions. Our study suggests the potential use of combining skin needling with rucinol and sophora-alpha compounds to achieve better results in melasma treatment compared to rucinol and sophora-alpha alone. PMID:22567235

  16. Glabridin nanosuspension for enhanced skin penetration: formulation optimization, in vitro and in vivo evaluation.

    Science.gov (United States)

    Wang, W P; Hul, J; Sui, H; Zhao, Y S; Feng, J; Liu, C

    2016-05-01

    Glabridin, a polyphenolic flavonoid from licorice, has inspired great interest for its antioxidant, anti-inflammatory and skin-lightening activities. However, low water solubility and poor stability of glabridin impedes its topical application in cosmetic products and therapies of dermal diseases. The purpose of this study was to develop a nanosuspension formulation of glabridin to improve its skin permeation. Glabridin nanosuspensions were prepared using anti-solvent precipitation-homogenization method, and Box-Behnken design was adopted to investigate the effects of crucial formulation variables on particle size and to optimize the nanosuspension formulation. The optimal formulation consisted of 0.25% glabridin, 0.47% Poloxamer 188 and 0.11% Polyvinylpyrrolidone K30, and the obtained nanosuspension showed an average particle size of 149.2 nm with a polydispersity index of 0.254. Furthermore, the nanosuspension exhibited significantly enhanced drug permeation flux of glabridin through rat skin with no lag phase both in vitro and in vivo, compared to the coarse suspension and physical mixture. The glabridin nanosuspension showed no significant particle aggregates and a drug loss of 5.46% after storage for 3 months at room temperature. With its enhanced skin penetration, the nanosuspension might be a more preferable formulation for topical administration of poorly soluble glabridin.

  17. Skin Needling to Enhance Depigmenting Serum Penetration in the Treatment of Melasma

    Directory of Open Access Journals (Sweden)

    G. Fabbrocini

    2011-01-01

    Full Text Available Melasma is a common hypermelanotic disorder affecting the facial area which has a considerable psychological impact on the patient. Managing melasma is a difficult challenge that requires long-term treatment with a number of topical agents, such as rucinol and sophora-alpha. Aims. We aim to compare the combined treatment of skin needling and depigmenting serum with that using depigmenting serum alone in the treatment of melasma, in order to evaluate the use of microneedles as a means to enhance the drug’s transdermal penetration. Methods. Twenty patients were treated with combined skin needling and depigmenting serum on one side of the face and with depigmenting serum alone on the other side. The outcome was evaluated periodically for up to two months using the Melasma Area Severity Index score and the Spectrocolorimeter X-Rite 968. Results. The side with combined treatment (skin needling + depigmenting serum presented a statistically significant reduction in MASI score and luminosity index (L levels compared to the side treated with depigmenting serum alone, and clinical symptoms were significantly improved. Conclusions. Our study suggests the potential use of combining skin needling with rucinol and sophora-alpha compounds to achieve better results in melasma treatment compared to rucinol and sophora-alpha alone.

  18. In vitro investigation of the follicular penetration of porcine ear skin using a nanoparticle-emulsion containing the antiseptic polihexanide In vitro investigation of the follicular penetration of porcine ear skin

    Science.gov (United States)

    Ulmer, M.; Patzelt, A.; Vergou, T.; Lademann, J.; Richter, H.; Kramer, A.; Müller, G.; Sterry, W.; Lange-Asschenfeldt, B.

    2012-05-01

    Earlier investigations regarding the distribution of the bacterial flora on the human skin demonstrate that the hair follicle acts as a bacterial reservoir, providing a quick source for secondary recontamination. These findings highlight the importance of the hair follicle as a target for modern antiseptics. In the present study, we have assessed the follicular penetration of a curcumin-labeled particle-associated antiseptic into porcine skin by laser scanning microscopy. Therefore, the follicular penetration depth of the curcumin-labeled particle-associated antiseptic was compared to the follicular penetration depth of curcumin-labeled particles without antiseptic. The investigation was performed in vitro using porcine skin biopsies. By superposition of the images acquired in the transmission and the fluorescent modus, it was possible to visualize the distribution of the fluorescent dye inside the hair follicles. Quantitative and qualitative results showed that both dispersions penetrated efficiently into the hair follicles. The average penetration depth of the particles with attached antiseptic polihexanide was significantly higher than that of particles without the attached antiseptic. Also, whilst very little sample preparation was needed, laser scanning microscopy was found to be an efficient tool to visualize the skin relief and in particular the hair follicle shaft and localize fluorescent markers within the skin tissue and hair follicles.

  19. Non-Darcian flow to a partially penetrating well in a confined aquifer with a finite-thickness skin

    Science.gov (United States)

    Feng, Qinggao; Wen, Zhang

    2016-08-01

    Non-Darcian flow to a partially penetrating well in a confined aquifer with a finite-thickness skin was investigated. The Izbash equation is used to describe the non-Darcian flow in the horizontal direction, and the vertical flow is described as Darcian. The solution for the newly developed non-Darcian flow model can be obtained by applying the linearization procedure in conjunction with the Laplace transform and the finite Fourier cosine transform. The flow model combines the effects of the non-Darcian flow, partial penetration of the well, and the finite thickness of the well skin. The results show that the depression cone spread is larger for the Darcian flow than for the non-Darcian flow. The drawdowns within the skin zone for a fully penetrating well are smaller than those for the partially penetrating well. The skin type and skin thickness have great impact on the drawdown in the skin zone, while they have little influence on drawdown in the formation zone. The sensitivity analysis indicates that the drawdown in the formation zone is sensitive to the power index ( n), the length of well screen ( w), the apparent radial hydraulic conductivity of the formation zone ( K r2), and the specific storage of the formation zone ( S s2) at early times, and it is very sensitive to the parameters n, w and K r2 at late times, especially to n, while it is not sensitive to the skin thickness ( r s).

  20. In vitro study of transdermal penetration and iontophoresis of hepatitis B vaccines through rat skin.

    Science.gov (United States)

    Xu, Ting; Xu, Yue-Hong; Wei, Min-Yan; Deng, Li-He; Wu, Chuan-Bin

    2011-06-01

    In vitro percutaneous delivery of hepatitis B vaccines was investigated in order to assess the penetration of vaccine under passive diffusion and iontophoresis conditions. The study was carried out using Franz vertical diffusion cell through the hairless abdominal skin of Sprague-Dawley (SD) rats. Enzyme-linked immunosorbent assay (ELISA) was used to determine the cumulative amount of permeation and the retention amount of drug in skin. Passive diffusion alone resulted in less skin permeation and retention of hepatitis B vaccines, only (2.1 +/- 0.1) ng x cm(-2) and (2.3 +/- 0.1) ng x cm(-2) after 24 h when the initial concentration of vaccine in the donor compartment was 23 microg x mL(-1) and 46 microg x mL(-1), respectively. After removing the stratum corneum, the permeation and retention amount of hepatitis B vaccines increased to (383.7 +/- 86.2) ng x cm(-2) and (16.8 +/- 4.6) ng x cm(-2), respectively, 171.6-folds and 2.1-folds more than that from its intact skin with the drug loaded at 46 microg x mL(-1). Iontophoresis induced a significant increase of cumulative and retention amount of hepatitis B vaccines through the skin (P iontophoresis significantly enhanced the permeation of hepatitis B vaccines (P Iontophoresis also significantly increased the amount of drug retained in the skin. After applying iontophoresis for 6 h, the amount of skin retention was nearly the same as passive diffusion for 24 h both from intact skin [(16.8 +/- 4.6) ng x cm(-2) vs (13.3 +/- 5.4) ng x cm(-2)] (P > 0.05) and tape-stripped skin [(36.7 +/- 14.1) ng x cm(-2) vs (26.8 +/- 11.2) ng x cm(-2)] (P > 0.05). Overall, these findings revealed that the transportation efficiency of bioactive substance like hepatitis B vaccines may be improved by iontophoresis, which can be potentially used in the field of transcutaneous immunization.

  1. Production of dissolvable microneedles using an atomised spray process: effect of microneedle composition on skin penetration.

    Science.gov (United States)

    McGrath, Marie G; Vucen, Sonja; Vrdoljak, Anto; Kelly, Adam; O'Mahony, Conor; Crean, Abina M; Moore, Anne

    2014-02-01

    Dissolvable microneedles offer an attractive delivery system for transdermal drug and vaccine delivery. They are most commonly formed by filling a microneedle mold with liquid formulation using vacuum or centrifugation to overcome the constraints of surface tension and solution viscosity. Here, we demonstrate a novel microneedle fabrication method employing an atomised spray technique that minimises the effects of the liquid surface tension and viscosity when filling molds. This spray method was successfully used to fabricate dissolvable microneedles (DMN) from a wide range of sugars (trehalose, fructose and raffinose) and polymeric materials (polyvinyl alcohol, polyvinylpyrrolidone, carboxymethylcellulose, hydroxypropylmethylcellulose and sodium alginate). Fabrication by spraying produced microneedles with amorphous content using single sugar compositions. These microneedles displayed sharp tips and had complete fidelity to the master silicon template. Using a method to quantify the consistency of DMN penetration into different skin layers, we demonstrate that the material of construction significantly influenced the extent of skin penetration. We demonstrate that this spraying method can be adapted to produce novel laminate-layered as well as horizontally-layered DMN arrays. To our knowledge, this is the first report documenting the use of an atomising spray, at ambient, mild processing conditions, to create dissolvable microneedle arrays that can possess novel, laminate layering.

  2. Cyclic Dipeptide Shuttles as a Novel Skin Penetration Enhancement Approach: Preliminary Evaluation with Diclofenac

    Science.gov (United States)

    Namjoshi, Sarika; Giralt, Ernest; Benson, Heather

    2016-01-01

    This study demonstrates the effectiveness of a peptide shuttle in delivering diclofenac into and through human epidermis. Diclofenac was conjugated to a novel phenylalanyl-N-methyl-naphthalenylalanine-derived diketopiperazine (DKP) shuttle and to TAT (a classical cell penetrating peptide), and topically applied to human epidermis in vitro. DKP and TAT effectively permeated into and through human epidermis. When conjugated to diclofenac, both DKP and TAT enhanced delivery into and through human epidermis, though DKP was significantly more effective. Penetration of diclofenac through human epidermis (to receptor) was increased by conjugation to the peptide shuttle and cell penetrating peptide with enhancement of 6x by DKP-diclofenac and 3x by TAT-diclofenac. In addition, the amount of diclofenac retained within the epidermis was significantly increased by peptide conjugation. COX-2 inhibition activity of diclofenac was retained when conjugated to DKP. Our study suggests that the peptide shuttle approach may offer a new strategy for targeted delivery of small therapeutic and diagnostic molecules to the skin. PMID:27548780

  3. Psoralen loaded liposomal nanocarriers for improved skin penetration and efficacy of topical PUVA in psoriasis.

    Science.gov (United States)

    Doppalapudi, Sindhu; Jain, Anjali; Chopra, Dhiraj Kumar; Khan, Wahid

    2017-01-01

    Psoralen in combination with ultraviolet A radiation (PUVA) is an FDA recommended therapy for clinical application in the management of severe recalcitrant psoriasis. Psoralen acts by intercalation of DNA and upon exposure to UV-A, it forms monoadducts which in turn induce apoptosis. Poor skin deposition, weak percutaneous permeability of psoralen and adverse effects of severe burning, blisters, pigmentation associated with conventional topical psoralen vehicles hinders the therapeutic efficacy and safety of topical PUVA. The aim of the present study is to formulate psoralen loaded liposomal nanocarriers for enhanced skin penetration, safety and efficacy of topical PUVA in psoriasis. Two different liposomal compositions i.e., cationic liposomes composed of DC-Chol, cholesterol and anionic liposomes composed of egg lecithin, cholesterol, tetramyristoyl cardiolipin were prepared for the topical delivery of psoralen. Liposomal carriers were characterized with respect to size, zeta potential, entrapment efficiency, stability, in vitro drug release and in vivo studies. Both liposomes were prepared with particle size of nearly 100nm. Zeta potential and entrapment efficiency of cationic liposomes were +25.8mV, 75.12% and anionic liposomes were -28.5mV, 60.08% respectively. Liposomal dermal distribution demonstrated higher penetration of both liposomal carriers over solution. Similarly, skin permeation study indicated 5 fold increase in permeation of psoralen with liposomal carriers. Topical application of psoralen liposomal gels on imiquimod induced psoriatic plaque model reduced the symptoms of psoriasis and levels of key psoriatic cytokines such as tumor necrosis factor-α, IL-17 and IL-22. In conclusion, the developed liposomal carriers of psoralen were found to be promising and can find application for optimal safety and efficacy of topical PUVA in psoriasis. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Study of the vitamins A, E and C esters penetration into the skin by confocal Raman spectroscopy in vivo

    Science.gov (United States)

    Mogilevych, Borys; Isensee, Debora; Rangel, Joao L.; Dal Pizzol, Carine; Martinello, Valeska C. A.; Dieamant, Gustavo C.; Martin, Airton A.

    2015-06-01

    Vitamins A, E and C play important role in skin homeostasis and protection. Hence, they are extensively used in many cosmetic and cosmeceutic products. However, their molecules are unstable, and do not easily penetrate into the skin, which drastically decreases its efficiency in topical formulations. Liposoluble derivative of the vitamin A - retinyl palmitate, vitamin E - tocopheryl acetate, and vitamin C - tetraisopalmitoyl ascorbic acid, are more stable, and are frequently used as an active ingredient in cosmetic products. Moreover, increased hydrophobicity of these molecules could lead to a higher skin penetration. The aim of this work is to track and compare the absorption of the liposoluble derivatives of the vitamins and their encapsulated form, into the healthy human skin in vivo. We used Confocal Raman Spectroscopy (CRS) that is proven to be helpful in label-free non-destructive investigation of the biochemical composition and molecular conformational analysis of the biological samples. The measurements were performed in the volar forearm of the 10 healthy volunteers. Skin was treated with both products, and Raman spectra were obtained after 15 min, 3 hours, and 6 hours after applying the formulation. 3510 Skin Composition Analyzer (River Diagnostics, The Netherlands) with 785 nm laser excitation was used to acquire information in the fingerprint region. Significant difference in permeation of the products was observed. Whereas only free form of retinyl palmitate penetrate the skin within first 15 minutes, all three vitamin derivatives were present under the skin surface in case of nanoparticulated form.

  5. The pretreatment effect of chemical skin penetration enhancers in transdermal drug delivery using iontophoresis.

    Science.gov (United States)

    Choi, E H; Lee, S H; Ahn, S K; Hwang, S M

    1999-01-01

    The transdermal drug delivery (TDD) system has largely been divided into physical, biochemical and chemical methods. Recently, combinations of these methods were introduced for more effective delivery with less side effects. We performed this study to identify the effectiveness and mechanism of TDD using the physical method, 'iontophoresis', plus the chemical method, 'pretreatment with chemical enhancer'. The action sites of chemical enhancers in the stratum corneum (SC) were observed by electron microscope. We also studied whether this combined method synergistically impaired the skin barrier. To confirm the synergistic effect on skin penetration by this combined method, we measured the blood glucose level after insulin iontophoresis following a chemical enhancer pretreatment in rabbits. The results were that (1) dilatation of the intercellular lipid layers of the SC and lacunae was prominent in pretreatment with chemical enhancers inducing high transepidermal water loss (TEWL); (2) the skin barrier impairment, with repeated treatments showing an increased TEWL and also epidermal proliferation, was increased with the chemical enhancers that showed a high TEWL immediately after treatment; (3) the combination of chemical enhancer pretreatment and iontophoresis showed no synergistic impairment of the skin barrier, and (4) the chemical enhancer pretreatment with greater impairment of the skin barrier could increase the delivery of insulin by iontophoresis. The results showed that a combination of chemical enhancer pretreatment and iontophoresis could deliver drugs more effectively than iontophoresis alone. Our proposed theory is that iontophoretic drug delivery may be easier through the dilated intercellular spaces of the SC which have a lower electrical impedance following the chemical enhancer pretreatment. Because the effect and the side effects in the combination are decided by the chemical enhancer rather than iontophoresis, the development of proper chemical

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

    Science.gov (United States)

    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.

  7. Schistosoma mansoni: quantification of skin penetration and early migration by differential external radioassay and autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Georgi, J.R. (New York State College of Veterinary Medicine, Ithaca (USA))

    1982-04-01

    Eleven gamma-emitting radionuclides (/sup 49/Sc, /sup 54/Mn, /sup 59/Fe, /sup 60/Co, /sup 65/Zn, /sup 75/Se (as selenomethionine, selenocystine, selenite and selenate), /sup 109/Cd, /sup 125/Sb, /sup 133/Ba, /sup 137/Cs and /sup 203/Hg) were screened as labelling agents for Schistosoma mansoni cercariae by incubation of infected Biomphalaria glabrata snails in radioactive solution. Only (/sup 75/Se)methionine yielded satisfactorily labelled cercariae. Differential external radioassay, a new technique employing partial body shielding within a total body counter, permitted separate estimation of tail and body radioactivity of conscious mice previously exposed by tail immersion to /sup 75/Se-labelled cercariae, with measurements repeated as often as desired. Approximately 39% of the /sup 75/Se present in emergent cercariae was retained by schistosomula transformed in vitro but this was subject to considerable variation, especially in schistosomula transformed in vivo. Secreted or catabolized label from penetrant cercariae and schistosomula was rapidly removed from the skin by the bloodstream. Numbers of schistosomula in tail skin were directly proportional to the number of reduced silver foci counted on tail autoradiograms; only a very small fraction of tail radioactivity represented unbound ('spurious') label. Migration of schistosomula away from skin was 50% complete at 3.8-4.3 days, as determined by probit analysis of autoradiographic data.

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

    Energy Technology Data Exchange (ETDEWEB)

    Szikszai, Z., E-mail: szikszai@atomki.h [Institute of Nuclear Research of the Hungarian Academy of Sciences, Debrecen (Hungary); Kertesz, Zs. [Institute of Nuclear Research of the Hungarian Academy of Sciences, Debrecen (Hungary); Bodnar, E. [Department of Dermatology, University of Debrecen, Medical and Health Science Center, Debrecen (Hungary); Major, I. [Institute of Nuclear Research of the Hungarian Academy of Sciences, Debrecen (Hungary); Borbiro, I. [Abiol Ltd., Debrecen (Hungary); Kiss, A.Z. [Institute of Nuclear Research of the Hungarian Academy of Sciences, Debrecen (Hungary); Hunyadi, J. [Department of Dermatology, University of Debrecen, Medical and Health Science Center, Debrecen (Hungary)

    2010-06-15

    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.

  9. Assay of tolnaftate in human skin samples after in vitro penetration studies using high performance liquid chromatography.

    Science.gov (United States)

    Kezutyte, Toma; Kornysova, Olga; Maruska, Audrius; Briedis, Vitalis

    2010-01-01

    Abstract: Tolnaftate, an antifungal of thiocarbamate class, is used topically in 1% formulations. Its penetration into skin layers is a prerequisite for tolnaftate action against dermatophytes. The aim of this work was to optimize and validate a simple, rapid, accurate and reproducible procedure for tolnaftate assay in human skin samples and to apply this procedure for in vitro tolnaftate penetration studies. High performance liquid chromatography (HPLC) method with UV detection was used to validate tolnaftate assay for linearity, specificity, accuracy, precision, limit of quantitation, limit of detection, drug extraction recovery and stability in skin extracts. In vitro tolnaftate penetration studies were carried out using flow-through diffusion cells, mounted with human skin. Epidermis and dermis, separated by heat-separation method, were extracted using ultrasonication in methanol. Linear range of the analytical procedure was within 0.6-100 pg/mL. The assay was specific, accurate (within-day and between-day recovery values were 98.2-104.2% and 98.7-101.4%, respectively) and precise (within-day and between-day imprecision was = 3.8%). Mean extraction recoveries of tolnaftate from epidermis and dermis were satisfactory and reaching 90%. In vitro skin penetration studies revealed that after application of 1% (w/w) tolnaftate solution in polyethylene glycol 400 for 24 hours, the mean amount of tolnaftate penetrating into the epidermis and dermis was 2.60 +/- 0.28 microg/cm2 and 0.92 +/- 0.12 microg/cm2, respectively. A validated reliable HPLC method could be recommended for biopharmaceutical evaluation of tolnaftate preparations and studies of pharmacokinetics in human skin after in vitro penetration studies.

  10. In vivo methods for the analysis of the penetration of topically applied substances in and through the skin barrier.

    Science.gov (United States)

    Lademann, J; Meinke, M C; Schanzer, S; Richter, H; Darvin, M E; Haag, S F; Fluhr, J W; Weigmann, H-J; Sterry, W; Patzelt, A

    2012-12-01

    The efficacy of a drug is characterized by its action mechanism and its ability to pass the skin barrier. In this article, different methods are discussed, which permit this penetration process to be analysed non-invasively. Providing qualitative and quantitative information, tape stripping is one of the oldest procedures for penetration studies. Although single cell layers of corneocytes are removed from the skin surface, this procedure is considered as non-invasive and is applicable exclusively to the stratum corneum. Recently, optical and spectroscopic methods have been used to investigate the penetration process. Fluorescence-labelled drugs can be easily detected in the skin by laser scanning microscopy. This method has the disadvantage that the dye labelling changes the molecular structures of the drug and consequently might influence the penetration properties. The penetration process of non-fluorescent substances can be analysed by Raman spectroscopy, electron paramagnetic resonance, CARS and multiphoton microscopic measurements. Using these methods, the concentration of the topically applied formulations in different depths of the stratum corneum can be detected by moving the laser focus from the skin surface deeper into the stratum corneum. The advantages and disadvantages of these methods will be discussed in this article.

  11. Penetration of benzene, toluene and xylenes contained in gasolines through human abdominal skin in vitro.

    Science.gov (United States)

    Adami, G; Larese, F; Venier, M; Barbieri, P; Lo Coco, F; Reisenhofer, E

    2006-12-01

    Few studies are available in literature on the risk for humans from skin exposure to gasolines. This work is focused on the in vitro skin penetration of benzene (carcinogenic substance), toluene and xylenes. We examined three commercial gasolines using the Franz diffusion cells and human abdominal full thickness skin. Gasoline composition was determined using a multi-dimensional gas chromatographic (MDGC) technique. Aromatic compounds into the receptor fluid, consisting of saline solution were quantitated by a gas chromatography technique equipped with a flame ionization detector (GC-FID) and coupled with a headspace-solid phase micro extraction system (HS-SPME). Among the three substances, benzene showed the highest average apparent permeability coefficient (K(p)=43.8x10(-5)cmh(-1)) compared to toluene (K(p)=6.48x10(-5)cmh(-1)) and xylenes (K(p)=0.84x10(-5)cmh(-1)). This value could be explained by the lower boiling point and higher water solubility of benzene. Lag times were about 1h for benzene and 2h for toluene and xylenes. Averaged total recoveries in the receptor fluid were 0.43% of dose for benzene, 0.06% for toluene and 0.008% for xylenes. A statistical significative difference (Student's t-test, Ptoluene between gasolines #1 (richer in aromatic compounds) and #3. The obtained apparent permeability coefficient are useful for determining the permeability of these aromatics components from gasolines of a different composition. Hands exposure risk, calculated using RfD and RfC as defined by US EPA, is critical for benzene. The risk of skin permeation of gasoline, and, in particular, of benzene, should be better evaluated for those workers who have a large potential for exposure. Adequate personal protective equipment should be used in the high exposure jobs, mainly for hands and forearms.

  12. Vehicle and enhancer effects on human skin penetration of aminophylline from cream formulations: evaluation in vivo.

    Science.gov (United States)

    Wang, Lai-Hao; Wang, Chia-Chen; Kuo, Su-Ching

    2007-01-01

    The effects of four essential oils (rosemary, ylang, lilacin, and peppermint oils), and three plant oils (jojoba oil, corn germ oil, and olive oil) on the permeation of aminophylline were studied using human skin. The permeation effects of these oils were compared with those of three chemical penetration enhancers. Although all oils enhanced the permeation of aminophylline, their effects were less than that of ethanol. Jojoba oil was found to be the most active, causing about a 32% peak height decrease of N-H bending absorbances in comparison with the control, while peppermint, lilacin, rosemary, and ylang oils caused 28%, 24%, 18%, and 12% peak height decreases, respectively. Microemulsions containing 10% jojoba oil and 30% corn germ oil were found to be superior vehicles for the percutaneous absorption of aminophylline. Comparision with results obtained from high-performance liquid chromatography shows good agreement.

  13. Design of Skin Penetration Enhancers Using Replacement Methods for the Selection of the Molecular Descriptors

    Directory of Open Access Journals (Sweden)

    Beshoy Abdelmalek

    2012-07-01

    Full Text Available Transdermal delivery of certain drugs is challenging because of skin barrier resistance. This study focuses on the implementation of feature-selection algorithms to design chemical penetration enhancers. A database, consisting of 145 polar and nonpolar chemicals, was chosen for the investigation. Replacement, enhanced replacement and stepwise algorithms were applied to identify relevant structural properties of these compounds. The descriptors were calculated using Molecular Modeling Pro™ Plus. Based on the coefficient of determination, the replacement methods outperformed the stepwise approach in selecting the features that best correlated with the flux enhancement ratio. An artificial neural network model was built to map a subset of descriptors from sixty-one nonpolar enhancers onto the output vector. The R2 value improved from 0.68, for a linear model, to 0.74, which shows that the improved framework might be effective in the design of compounds with user-defined properties.

  14. Natural oils affect the human skin integrity and the percutaneous penetration of benzoic acid dose-dependently

    DEFF Research Database (Denmark)

    Nielsen, Jesper Bo

    2006-01-01

    Abstract: Natural oils are extensively used in cosmetics and as treatment for a growing number of more or less specific ailments. Skin irritation and cases of allergy have repeatedly been described in the literature following exposure to these oils. The present study evaluated the extent to which...... three natural oils (eucalyptus oil, tea tree oil, peppermint oil) would affect the skin integrity and the percutaneous penetration of benzoic acid when applied topically in relevant concentrations. An experimental in vitro model using static diffusion cells mounted with human breast or abdominal skin...... was applied. The three natural oils decreased the skin integrity dose-dependently. Concomitant dermal exposure to low concentrations of peppermint oil reduced the percutaneous penetration of benzoic acid. The present study lends support to the notion that low concentrations of peppermint oil may act...

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

    Science.gov (United States)

    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.

  16. Photoacoustic study of the penetration kinetics of nimesulid into human skin

    Energy Technology Data Exchange (ETDEWEB)

    Barja, P R; Veloso, D J D V, E-mail: barja@univap.b [Research and Development Institute, UNIVAP, Av. Shishima Hifumi 2911, Sao Jose dos Campos, SP, 12209-010 (Brazil)

    2010-03-01

    The photoacoustic (PA) effect is observed when modulated (or pulsed) light is absorbed by a sample inside a closed chamber and converted in heat, generating acoustic waves; PA measurements have been employed to evaluate transdermal penetration of topically applied drugs. Phonophoresis is the utilization of ultrasonic (US) energy to enhance absorption of drugs across the epidermal barrier, and its usefulness has been shown by PA measurements. The aim of the present work was to determine the characteristic absorption times of the anti-inflammatory Nimesulid (gel) in human skin, with and without help of therapeutic phonophoresis. After local cleaning, measurements were performed in the forearm of each volunteer before Nimesulid application and for different times after application through massage with the US equipment head; the protocol was repeated for the opposite forearm, but without US emission. Curves of the PA signal level as a function of time were adjusted by a Boltzmann equation, leading to the determination of the characteristic absorption time (about 12 minutes). No significant gain was observed in Nimesulid absorption with the utilization of US radiation, indicating that topic application of Nimesulid does not require the use of phonophoresis, due to the natural fast penetration of the Nimesulid gel.

  17. In vitro skin penetration of clobetasol from lipid nanoparticles: drug extraction and quantitation in different skin layers

    Directory of Open Access Journals (Sweden)

    Luís Antônio Dantas Silva

    2012-12-01

    Full Text Available Clobetasol propionate (CP is a potent topical corticosteroid that causes several cutaneous and systemic side effects. In the present work, CP was encapsulated in nanostructured lipid carriers (NLCs to increase drug retention in the outer skin layers and improve the safety of topical therapy. NLCs were prepared using a microemulsion technique with a mixture of lecithin, taurodeoxycholate, stearic acid, and oleic acid. In vitro penetration studies were performed in a modified Franz-type diffusion cell, and porcine ears were used as a model of human skin. A simple and sensitive liquid chromatographic method was developed and validated for clobetasol determination in different skin layers. NLCs presented uniform size distribution, high zeta potentialand entrapment efficiency values (> 98%. The analytical procedure was validated according to FDA guidelines. Clobetasol recoveries from skin samples were higher than 85%, with no interference of skin components and NLC ingredients. In experiments, after 6 h, a higher drug accumulation in the stratum corneum arising from NLCs compared to aqueous CP solution was observed. Thus, the NLCs demonstrated high potential for targeting CP to the skin and ensuring drug accumulation in the stratum corneum.Proprionato de clobetasol (CP é um potente corticóide tópico, que apresenta vários efeitos adversos cutâneos e sistêmicos. No presente trabalho, CP foi encapsulado em carreadores lipídicos nanoestruturados (NLCs visando aumentar a retenção do fármaco nas camadas superficiais da pele e a segurança da terapia tópica. NLCs foram preparados usando a técnica de diluição de microemulsão com mistura de lecitina, taurodesoxicolato, ácido esteárico e ácido oléico. Estudos de penetração in vitro foram realizados em células de difusão de Franz modificadas usando pele de orelha de porco como modelo de pele humana. Um método simples e sensível de cromatografia líquida foi desenvolvido e validado para

  18. Penetration of spherical and rod-like gold nanoparticles into intact and barrier-disrupted human skin

    Science.gov (United States)

    Graf, Christina; Nordmeyer, Daniel; Ahlberg, Sebastian; Raabe, Jörg; Vogt, Annika; Lademann, Jürgen; Rancan, Fiorenza; Rühl, Eckart

    2015-03-01

    The penetration of spherical and rod-like gold nanoparticles into human skin is reported. Several skin preparation techniques are applied, including cryo techniques, such as plunge freezing and freeze drying, and the use of wet cells. Their advantages and drawbacks for observing nanoparticle uptake are discussed. Independent of the particle shape no uptake into intact skin is observed by a combination of imaging approaches, including scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and scanning X-ray microscopy (STXM). These results are discussed along with suitable skin preparation approaches. Experiments on barrier-disrupted skin, i.e. mechanical lesions made by pricking, indicate, however, that gold particles can be identified deep in the dermis, as follows from STXM studies on wet skin samples.

  19. Efficiency of low-frequency ultrasound sonophoresis in skin penetration of histamine: a randomized study in humans.

    Science.gov (United States)

    Maruani, Annabel; Vierron, Emilie; Machet, Laurent; Giraudeau, Bruno; Boucaud, Alain

    2010-01-29

    Low-frequency ultrasound (US) applied to skin (sonophoresis) has been investigated to enhance the transdermal transport of various drugs. Histamine is usually used in allergy investigations. We aimed to investigate, in a randomized study, the transdermal penetration of histamine with sonophoresis. Ten subjects were included. Their right forearm was divided into three zones, which were randomly assigned a treatment: no US, US(1) (I(1)=2.72 W/cm(2)), US(2) (I(2)=3.50 W/cm(2)). The primary outcome was area of induced papule, which revealed histamine penetration. Secondary outcomes were echographic measurement of papule (skin thickness) and pruritus. Measurements were taken immediately after US application and after 30 min, 2 h and 24 h. Arm zones without US application showed no papules induced by histamine; 9/10 subjects receiving US showed papules. Their mean size increased with increased intensity of US but not significantly. The skin thickness increased with US. Pruritus occurred in 7/10 cases after US and histamine. The adverse events were skin erythema, pain and tinnitus. Though this study included a few number of patients, it confirms that sonophoresis enhances skin penetration of histamine. This technology could be used at therapeutic levels: histamine could be used with sonophoresis as a positive control in allergy testing instead of prick tests, which involve skin disruption with a lancet. 2009 Elsevier B.V. All rights reserved.

  20. Stress relaxation analysis facilitates a quantitative approach towards antimicrobial penetration into biofilms.

    Science.gov (United States)

    He, Yan; Peterson, Brandon W; Jongsma, Marije A; Ren, Yijin; Sharma, Prashant K; Busscher, Henk J; van der Mei, Henny C

    2013-01-01

    Biofilm-related infections can develop everywhere in the human body and are rarely cleared by the host immune system. Moreover, biofilms are often tolerant to antimicrobials, due to a combination of inherent properties of bacteria in their adhering, biofilm mode of growth and poor physical penetration of antimicrobials through biofilms. Current understanding of biofilm recalcitrance toward antimicrobial penetration is based on qualitative descriptions of biofilms. Here we hypothesize that stress relaxation of biofilms will relate with antimicrobial penetration. Stress relaxation analysis of single-species oral biofilms grown in vitro identified a fast, intermediate and slow response to an induced deformation, corresponding with outflow of water and extracellular polymeric substances, and bacterial re-arrangement, respectively. Penetration of chlorhexidine into these biofilms increased with increasing relative importance of the slow and decreasing importance of the fast relaxation element. Involvement of slow relaxation elements suggests that biofilm structures allowing extensive bacterial re-arrangement after deformation are more open, allowing better antimicrobial penetration. Involvement of fast relaxation elements suggests that water dilutes the antimicrobial upon penetration to an ineffective concentration in deeper layers of the biofilm. Next, we collected biofilms formed in intra-oral collection devices bonded to the buccal surfaces of the maxillary first molars of human volunteers. Ex situ chlorhexidine penetration into two weeks old in vivo formed biofilms followed a similar dependence on the importance of the fast and slow relaxation elements as observed for in vitro formed biofilms. This study demonstrates that biofilm properties can be derived that quantitatively explain antimicrobial penetration into a biofilm.

  1. Nuclear microprobe investigation of the penetration of ultrafine zinc oxide into human skin affected by atopic dermatitis

    Energy Technology Data Exchange (ETDEWEB)

    Szikszai, Z., E-mail: szikszai@atomki.hu [Institute of Nuclear Research of the Hungarian Academy of Sciences, Debrecen (Hungary); Kertesz, Zs. [Institute of Nuclear Research of the Hungarian Academy of Sciences, Debrecen (Hungary); Bodnar, E. [Department of Dermatology, University of Debrecen, Medical and Health Science Center, Debrecen (Hungary); Borbiro, I. [Abiol Ltd., Debrecen (Hungary); Angyal, A.; Csedreki, L.; Furu, E.; Szoboszlai, Z.; Kiss, A.Z. [Institute of Nuclear Research of the Hungarian Academy of Sciences, Debrecen (Hungary); Hunyadi, J. [Department of Dermatology, University of Debrecen, Medical and Health Science Center, Debrecen (Hungary)

    2011-10-15

    Skin penetration is one of the potential routes for nanoparticles to gain access into the human body. 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 particle size smaller than 200 nm makes the product more transparent compared to formulations containing coarser particles. The present study continues the work carried out in the frame of the NANODERM: 'Quality of skin as a barrier to ultrafine particles' European project and complements our previous investigations on human skin with compromised barrier function. Atopic dermatitis (a type of eczema) is an inflammatory, chronically relapsing, non-contagious skin disease. It is very common in children but may occur at any age. The exact cause of atopic dermatitis is unknown, but is likely due to a combination of impaired barrier function together with a malfunction in the body's immune system. In this study, skin samples were obtained from two patients suffering from atopic dermatitis. Our results indicate that the ultrafine zinc oxide particles, in a hydrophobic basis gel with an application time of 2 days or 2 weeks, have penetrated deeply into the stratum corneum in these patients. On the other hand, penetration into the stratum spinosum was not observed even in the case of the longer application time.

  2. Nuclear microprobe investigation of the penetration of ultrafine zinc oxide into human skin affected by atopic dermatitis

    Science.gov (United States)

    Szikszai, Z.; Kertész, Zs.; Bodnár, E.; Borbíró, I.; Angyal, A.; Csedreki, L.; Furu, E.; Szoboszlai, Z.; Kiss, Á. Z.; Hunyadi, J.

    2011-10-01

    Skin penetration is one of the potential routes for nanoparticles to gain access into the human body. 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 particle size smaller than 200 nm makes the product more transparent compared to formulations containing coarser particles. The present study continues the work carried out in the frame of the NANODERM: “Quality of skin as a barrier to ultrafine particles” European project and complements our previous investigations on human skin with compromised barrier function. Atopic dermatitis (a type of eczema) is an inflammatory, chronically relapsing, non-contagious skin disease. It is very common in children but may occur at any age. The exact cause of atopic dermatitis is unknown, but is likely due to a combination of impaired barrier function together with a malfunction in the body's immune system. In this study, skin samples were obtained from two patients suffering from atopic dermatitis. Our results indicate that the ultrafine zinc oxide particles, in a hydrophobic basis gel with an application time of 2 days or 2 weeks, have penetrated deeply into the stratum corneum in these patients. On the other hand, penetration into the stratum spinosum was not observed even in the case of the longer application time.

  3. Plasmin-driven fibrinolysis facilitates skin tumor growth in a gender-dependent manner

    DEFF Research Database (Denmark)

    Hald, Andreas; Eickhardt, Hanne; Maerkedahl, Rasmus Baadsgaard

    2012-01-01

    Rearrangement of the skin during wound healing depends on plasmin and plasminogen, which serve to degrade fibrin depositions in the provisional matrix and thereby facilitate keratinocyte migration. In the current study, we investigated whether plasmin and plasminogen likewise played a role during...... by superimposing heterozygous fibrinogen deficiency on Plg(-)(/)(-) mice. Tumors derived from these Fib(-)(/+);Plg(-)(/)(-) mice displayed a significantly decreased level of tumor thrombosis compared with Plg(-)(/)(-) mice. In summary, these data indicate that plasmin-driven fibrinolysis facilitates tumor growth...... by maintaining patency of the tumor vasculature.-Hald, A., Eickhardt, H., Maerkedahl, R. B., Feldborg, C. W., Egerod, K. L., Engelholm. L. H., Laerum, O. D., Lund, L. R., Rønø, B. Plasmin-driven fibrinolysis facilitates skin tumor growth in a gender-dependent manner....

  4. Synthesis of fluorescent C24-ceramide: evidence for acyl chain length dependent differences in penetration of exogenous NBD-ceramides into human skin.

    Science.gov (United States)

    Novotný, Jakub; Pospechová, Katerina; Hrabálek, Alexandr; Cáp, Robert; Vávrová, Katerina

    2009-12-15

    Topical skin lipid supplementation may provide opportunities for controlling ceramide (Cer) deficiency in skin diseases such as atopic dermatitis or psoriasis. Here we describe the synthesis of a long-chain 7-nitrobenzo[c][1,2,5]oxadiazol-4-yl (NBD)-labeled Cer and its different penetration through human skin compared to widely used short-chain fluorescent Cer tools.

  5. Needle-free jet injections: dependence of jet penetration and dispersion in the skin on jet power.

    Science.gov (United States)

    Schramm-Baxter, Joy; Mitragotri, Samir

    2004-07-07

    Jet injection is a needle-free drug delivery method in which a high-speed stream of fluid impacts the skin and delivers drugs. Although a number of jet injectors are commercially available, especially for insulin delivery, a quantitative understanding of the energetics of jet injection is still lacking. Here, we describe the dependence of jet injections into human skin on the power of the jet. Dermal delivery of liquid jets was quantified using two measurements, penetration of a radiolabeled solute, mannitol, into skin and the shape of jet dispersion in the skin which was visualized using sulforhodamine B (SRB). The power of the jet at the nozzle was varied from 1 to 600 W by independently altering the nozzle diameter (30-560 microm) and jet velocity (100-200 m/s). The dependence of the amount of liquid delivered in the skin and the geometric measurements of jet dispersion on nozzle diameter and jet velocity was captured by a single parameter, jet power. Additional experiments were performed using a model material, polyacrylamide gel, to further understand the dependence of jet penetration on jet power. These experiments demonstrated that jet power also effectively describes gel erosion due to liquid impingement.

  6. Relative Penetration of Zinc Oxide and Zinc Ions into Human Skin after Application of Different Zinc Oxide Formulations.

    Science.gov (United States)

    Holmes, Amy M; Song, Zhen; Moghimi, Hamid R; Roberts, Michael S

    2016-02-23

    Zinc oxide (ZnO) is frequently used in commercial sunscreen formulations to deliver their broad range of UV protection properties. Concern has been raised about the extent to which these ZnO particles (both micronized and nanoparticulate) penetrate the skin and their resultant toxicity. This work has explored the human epidermal skin penetration of zinc oxide and its labile zinc ion dissolution product that may potentially be formed after application of ZnO nanoparticles to human epidermis. Three ZnO nanoparticle formulations were used: a suspension in the oil, capric caprylic triglycerides (CCT), the base formulation commonly used in commercially available sunscreen products; an aqueous ZnO suspension at pH 6, similar to the natural skin surface pH; and an aqueous ZnO suspension at pH 9, a pH at which ZnO is stable and there is minimal pH-induced impairment of epidermal integrity. In each case, the ZnO in the formulations did not penetrate into the intact viable epidermis for any of the formulations but was associated with an enhanced increase in zinc ion fluorescence signal in both the stratum corneum and the viable epidermis. The highest labile zinc fluorescence was found for the ZnO suspension at pH 6. It is concluded that, while topically applied ZnO does not penetrate into the viable epidermis, these applications are associated with hydrolysis of ZnO on the skin surface, leading to an increase in zinc ion levels in the stratum corneum, thence in the viable epidermis and subsequently in the systemic circulation and the urine.

  7. Effect of Penetration Enhancer Containing Vesicles on the Percutaneous Delivery of Quercetin through New Born Pig Skin

    Directory of Open Access Journals (Sweden)

    Maria Manconi

    2011-08-01

    Full Text Available Quercetin (3,3′,4′,5,7-pentahydroxyflavone exerts multiple pharmacological effects: anti-oxidant activity, induction of apoptosis, modulation of cell cycle, anti-mutagenesis, and anti-inflammatory effect. In topical formulations quercetin inhibits oxidative skin damage and the inflammatory processes induced by solar UV radiation. In this work, quercetin (2 mg/mL was loaded in vesicular Penetration Enhancer containing Vesicles (PEVs, prepared using a mixture of lipids (Phospholipon® 50, P50 and one of four selected hydrophilic penetration enhancers: Transcutol® P, propylene glycol, polyethylene glycol 400, and Labrasol® at the same concentration (40% of water phase. Photon Correlation Spectroscopy results showed a mean diameter of drug loaded vesicles in the range 80–220 nm. All formulations showed a negative surface charge and incorporation efficiency in the range 48–75%. Transmission Electron Microscopy confirmed that size and morphology varied as a function of the used penetration enhancer. The influence of PEVs on ex vivo quercetin (transdermal delivery was evaluated using Franz-type diffusion cells, new born pig skin and Confocal Laser Scanning Microscopy. Results showed that drug delivery is affected by the penetration enhancer used in the PEVs' formulation.

  8. In vitro human skin penetration model for organophosphorus compounds with different physicochemical properties.

    Science.gov (United States)

    Thors, L; Koch, B; Koch, M; Hägglund, L; Bucht, A

    2016-04-01

    A flow-through diffusion cell was validated for in vitro human epidermal penetration studies of organophosphorus compounds (OPCs) applied by infinite dosing. By testing OPCs with similar molecular weight but different physicochemical properties, it was shown that hydrophilic and lipophilic properties are major determinants for the penetration rate. Lipophilic OPCs displayed maximum cumulative penetration in the 20-75% agent concentration range whereas the hydrophilic OPCs displayed maximum cumulative penetration at 10 or 20% agent concentration. Low penetration was observed for all agents at 1% agent concentration or when applied as neat agents. The impact of the receptor solution composition was evaluated by comparing the penetration using receptor solutions of different ratios of ethanol and water. For diluted OPCs, a high concentration of ethanol in the receptor solution significantly increased the penetration compared to lower concentrations. When OPCs were applied as neat agents, the composition of the receptor solution only affected the penetration for one of four tested compounds. In conclusion, the flow-through diffusion cell was useful for examining the penetration of OPCs through the epidermal membrane. It was also demonstrated that the penetration rates of OPCs are strongly influenced by dilution in water and the receptor fluid composition.

  9. Evaluation of Efficacy and Safety of Drugs Penetrated into Skin Using Their Physicochemical Parameters

    OpenAIRE

    押坂, 勇志; 藤堂, 浩明; 杉林, 堅次

    2012-01-01

    Skin has been paid attention as a site of application of prescription drugs, over-the-counter drugs (non-prescription drugs) and cosmetics. Skin permeation and skin concentration of the compounds should be considered after topical administration, as well as their blood concentration to evaluate efficacy and safety. Since the evaluation of the amount of drugs permeated through skin is important for topically applied drugs, studies on the skin permeation has been greatly advanced. In addition, ...

  10. Development and validation of an alternative disturbed skin model by mechanical abrasion to study drug penetration

    OpenAIRE

    Schlupp, P.; M. Weber; T. Schmidts; Geiger, K.; Runkel, F.

    2014-01-01

    Pharmaceuticals and cosmetics for dermal application are usually tested on healthy skin, although the primary permeation barrier, the stratum corneum, is often impaired by skin diseases or small skin lesions, especially on the hands. These skin conditions can considerably influence the permeation of chemicals and drugs. Furthermore, risk assessment for example of nanoparticles should be performed under various skin conditions to reflect the true circumstances. Therefore, an alternative and re...

  11. High-Throughput Screening of Potential Skin Penetration-Enhancers Using Stratum Corneum Lipid Liposomes: Preliminary Evaluation for Different Concentrations of Ethanol

    Science.gov (United States)

    Kitao, Yuki

    2017-01-01

    In this study, we developed a technique for high-throughput screening (HTS) of skin penetration-enhancers using stratum corneum lipid liposomes (SCLLs). A fluorescent marker, sodium fluorescein (FL), entrapped in SCLLs was prepared to provide a preliminary evaluation of the effect of different concentrations of ethanol on the disruption effect of SCLLs, which is an alternative for skin penetration-enhancing effects. In addition, SCLLs containing a fluorescent probe (DPH, TMA-DPH, or ANS) were also prepared and utilized to investigate SCLL fluidity. The results using SCLL-based techniques were compared with conventional skin permeation and skin impedance test using hairless rat skin. The obtained correlations were validated between FL leakage, SCLL fluidity with various probes, or skin impedance and increases in the skin permeation enhancement ratio (ER) of caffeine as a model penetrant. As a result, FL leakage and SCLL fluidity using ANS were considered to be good indices for the skin penetration-enhancing effect, suggesting that the action of ethanol on the SC lipid and penetration-enhancing is mainly on the polar head group of intercellular lipids. In addition, this screening method using SCLL could be utilized as an alternative HTS technique for conventional animal tests. Simultaneously, the method was found to be time-saving and sensitive compared with a direct assay using human and animal skins. PMID:28321359

  12. Enhancement of the in vitro penetration of quercetin through pig skin by combined microneedles and lipid microparticles.

    Science.gov (United States)

    Paleco, Roberto; Vučen, Sonja R; Crean, Abina M; Moore, Anne; Scalia, Santo

    2014-09-10

    Silicon microneedle patches were investigated, alone or in combination with lipid microparticles (LMs), as a system to improve the in vitro skin penetration of the antioxidant flavonoid, quercetin. LMs loaded with quercetin were prepared by melt emulsification and sonication. The flavonoid content of LMs was 11.7±0.3% and their mean diameter and polydispersity index were 8.1 μm and 0.66, respectively. Emulsions containing quercetin, free or microencapsulated, were applied to untreated- or microneedle-treated pig skin mounted in Franz diffusion cells. The amount of flavonoid penetrated into the stratum corneum and viable epidermis were measured by HPLC, after validated tape-stripping and bead mill homogenization procedures, respectively. Compared to intact skin, a marked increase in quercetin levels permeated into the stratum corneum (from 1.19 ± 0.12 μg/cm(2) to 2.23 ± 0.54 μg/cm(2)) and viable epidermis (from 0.10 ± 0.01 μg/cm(2) to 0.56 ± 0.27 μg/cm(2)) was achieved when skin was treated with the flavonoid-loaded LMs in combination with microneedle arrays. Conversely, perforation of the cutaneous surface by microneedles did not produce any significant improvement in the skin penetration of non-encapsulated quercetin. The enhanced (5.5-fold) intra-epidermal delivery of quercetin attained by the LM/microneedle strategy described here, is particularly relevant since the main quercetin site of action is in the epidermis.

  13. Fluorometric quantification of protoporphyrin IX in biological skin samples from in vitro penetration/permeation studies

    Directory of Open Access Journals (Sweden)

    Fábia Cristina Rossetti

    2010-12-01

    Full Text Available A fluorometric analytical method was developed for quantification of protoporphyrin IX (PpIX in skin samples and receptor phase solution after in vitro cutaneous penetration/permeation studies. Analytical conditions used were: excitation and emission wavelengths: 400 nm and 632 nm; bandwidth: 0.5 nm; excitation and emission slits: 10/10. PpIX was recovered from two different layers of skin, the stratum corneum (SC and the epidermis plus dermis ([E+D], by vortex homogenization, probe and bath sonication, using DMSO as an extraction solvent. The detection and quantification limits were 0.002 and 0.005 μg/mL, respectively. The assay was linear from 0.005 - 0.5 μg/mL. The within-day and between-day assay precision and accuracy in DMSO and receptor phase solution were each studied at the two concentration levels 0.04 and 0.2 μg/mL, and 0.01 and 0.08 μg/mL, respectively. The coefficients of variation and deviation from the theoretical values were lower than 5%. The skin recovery of PpIX from SC and [E+D] layers using two different concentrations (0.5 and 1.0 μg/mL were all above 90.0%. The method described has potential application to in vitro penetration/permeation studies of PpIX using porcine skin as a biological membrane model.Um método analítico por espectrofluorimetria foi desenvolvido para quantificar a protoporfirina IX (Pp IX em amostras de pele e fase receptora após a realização de testes in vitro de penetração/permeação cutâneas. As condições analíticas utilizadas foram: comprimentos de onda de excitação e emissão: 400 nm e 632 nm; largura de banda: 0,5 nm; fendas de excitação e emissão: 10/10. A PpIX foi extraída de amostras de estrato córneo (EC e da epiderme sem estrato córneo + derme ([E+D] através da agitação em vórtex e sonicação por haste e banho, utilizando-se o DMSO como solvente extrator. O limite de detecção e quantificação foram, respectivamente, de 0,002 e 0,005 μg/mL. O método mostrou

  14. Development and validation of an alternative disturbed skin model by mechanical abrasion to study drug penetration.

    Science.gov (United States)

    Schlupp, P; Weber, M; Schmidts, T; Geiger, K; Runkel, F

    2014-01-01

    Pharmaceuticals and cosmetics for dermal application are usually tested on healthy skin, although the primary permeation barrier, the stratum corneum, is often impaired by skin diseases or small skin lesions, especially on the hands. These skin conditions can considerably influence the permeation of chemicals and drugs. Furthermore, risk assessment for example of nanoparticles should be performed under various skin conditions to reflect the true circumstances. Therefore, an alternative and reproducible method for a high throughput of skin samples with impaired skin barrier was developed and verified by skin permeation studies (25 h) of caffeine, sorbic acid and testosterone compared to healthy (untreated) and tape-stripped skin. Skin barrier disruption was controlled by TEWL measurement. Skin permeation of the three substances was increased in tape-stripped and abraded skin compared to untreated skin due to the reduced barrier integrity. Enhancement of drug uptake was highest for the most hydrophilic substance, caffeine, followed by sorbic acid and lipophilic testosterone. No significant difference in drug uptake studies was observed between the new abrasion method with an aluminum-coated sponge and the tape-stripping method. The obtained results demonstrate that this abrasion method is an alternative way to achieve a disturbed skin barrier for drug and chemical uptake studies.

  15. Dermal uptake and percutaneous penetration of ten flame retardants in a human skin ex vivo model.

    Science.gov (United States)

    Frederiksen, Marie; Vorkamp, Katrin; Jensen, Niels Martin; Sørensen, Jens Ahm; Knudsen, Lisbeth E; Sørensen, Lars S; Webster, Thomas F; Nielsen, Jesper B

    2016-11-01

    The dermal uptake and percutaneous penetration of ten organic flame retardants was measured using an ex vivo human skin model. The studied compounds were DBDPE, BTBPE, TBP-DBPE, EH-TBB, BEH-TEBP, α, β and γ-HBCDD as well as syn- and anti-DDC-CO. Little or none of the applied flame retardants was recovered in either type of the receptor fluids used (physiological and worst-case). However, significant fractions were recovered in the skin depot, particularly in the upper skin layers. The primary effect of the worst-case receptor fluid was deeper penetration into the skin. The recovered mass was used to calculate lower- and upper-bound permeability coefficients kp. Despite large structural variation between the studied compounds, a clear, significant decreasing trend of kp was observed with increasing log Kow. The results indicate that the dermis may provide a significant barrier for these highly lipophilic compounds. However, based on our results, dermal uptake should be considered in exposure assessments, though it may proceed in a time-lagged manner compared to less hydrophobic compounds.

  16. Evaluation of Skin Penetration of Diclofenac from a Novel Topical Non Aqueous Solution: A Comparative Bioavailability Study.

    Science.gov (United States)

    Nivsarkar, Manish; Maroo, Sanjaykumar H; Patel, Ketan R; Patel, Dixit D

    2015-12-01

    Different topical formulations of diclofenac have varying skin penetration profile. Recent advances in science and technology has led to the development of many new formulations of drugs for topical drug delivery. One such technological development has led to the innovation of Dynapar QPS, a novel, non-aqueous, quick penetrating solution (QPS) of diclofenac diethylamine. This study was aimed to measure the total exposure from the drug penetrating the skin in healthy human subjects and comparing the relative systemic bioavailability of Dynapar QPS(®) with diclofenac emulgel. A 200 mg of diclofenac from either Dynapar QPS(®) (5 ml) or emulgel (20 g) was applied on back of subject as per the randomisation schedule. Blood samples were collected up to 16 hours post drug application. Plasma concentration of diclofenac was measured by pre-validated HPLC method. Pharmacokinetic (PK) parameters like Cmax, Tmax, t1/2, AUC0-t, AUC0-∞, and Kel, of diclofenac were determined for both the formulations. Mean Cmax after administration of Dynapar QPS(®) and diclofenac emulgel were 175.93 and 40.04 ng/ml, respectively. Tmax of diclofenac was almost half with QPS compared to emulgel (5.24 hrs versus 9.53 hrs respectively). The mean AUC0-t and AUC0-∞ after administration of Dynapar QPS(®) was higher as compared to diclofenac emulgel (AUC0-t: 1224.19 versus 289.78 ng.h/ml, respectively; AUC0-∞: 1718.21 versus 513.83 ng.h/ml, respectively). None of the subject experienced any adverse event during the study. The results indicate an enhanced penetration and subsequent absorption of diclofenac from Dynapar QPS(®) as compared to diclofenac emulgel. Higher penetration is likely to translate into better pain relief in patients.

  17. HIV-associated disruption of mucosal epithelium facilitates paracellular penetration by human papillomavirus.

    Science.gov (United States)

    Tugizov, Sharof M; Herrera, Rossana; Chin-Hong, Peter; Veluppillai, Piri; Greenspan, Deborah; Michael Berry, J; Pilcher, Christopher D; Shiboski, Caroline H; Jay, Naomi; Rubin, Mary; Chein, Aung; Palefsky, Joel M

    2013-11-01

    The incidence of human papillomavirus (HPV)-associated epithelial lesions is substantially higher in human immunodeficiency virus (HIV)-infected individuals than in HIV-uninfected individuals. The molecular mechanisms underlying the increased risk of HPV infection in HIV-infected individuals are poorly understood. We found that HIV proteins tat and gp120 were expressed within the oral and anal mucosal epithelial microenvironment of HIV-infected individuals. Expression of HIV proteins in the mucosal epithelium was correlated with the disruption of epithelial tight junctions (TJ). Treatment of polarized oral, cervical and anal epithelial cells, and oral tissue explants with tat and gp120 led to disruption of epithelial TJ and increased HPV pseudovirion (PsV) paracellular penetration in to the epithelium. PsV entry was observed in the basal/parabasal cells, the cells in which the HPV life cycle is initiated. Our data suggest that HIV-associated TJ disruption of mucosal epithelia may potentiate HPV infection and subsequent development of HPV-associated neoplasia.

  18. Confocal Raman microscopy and multivariate statistical analysis for determination of different penetration abilities of caffeine and propylene glycol applied simultaneously in a mixture on porcine skin ex vivo.

    Science.gov (United States)

    Mujica Ascencio, Saul; Choe, ChunSik; Meinke, Martina C; Müller, Rainer H; Maksimov, George V; Wigger-Alberti, Walter; Lademann, Juergen; Darvin, Maxim E

    2016-07-01

    Propylene glycol is one of the known substances added in cosmetic formulations as a penetration enhancer. Recently, nanocrystals have been employed also to increase the skin penetration of active components. Caffeine is a component with many applications and its penetration into the epidermis is controversially discussed in the literature. In the present study, the penetration ability of two components - caffeine nanocrystals and propylene glycol, applied topically on porcine ear skin in the form of a gel, was investigated ex vivo using two confocal Raman microscopes operated at different excitation wavelengths (785nm and 633nm). Several depth profiles were acquired in the fingerprint region and different spectral ranges, i.e., 526-600cm(-1) and 810-880cm(-1) were chosen for independent analysis of caffeine and propylene glycol penetration into the skin, respectively. Multivariate statistical methods such as principal component analysis (PCA) and linear discriminant analysis (LDA) combined with Student's t-test were employed to calculate the maximum penetration depths of each substance (caffeine and propylene glycol). The results show that propylene glycol penetrates significantly deeper than caffeine (20.7-22.0μm versus 12.3-13.0μm) without any penetration enhancement effect on caffeine. The results confirm that different substances, even if applied onto the skin as a mixture, can penetrate differently. The penetration depths of caffeine and propylene glycol obtained using two different confocal Raman microscopes are comparable showing that both types of microscopes are well suited for such investigations and that multivariate statistical PCA-LDA methods combined with Student's t-test are very useful for analyzing the penetration of different substances into the skin.

  19. Chitosan improves anti-biofilm efficacy of gentamicin through facilitating antibiotic penetration.

    Science.gov (United States)

    Mu, Haibo; Guo, Fan; Niu, Hong; Liu, Qianjin; Wang, Shunchun; Duan, Jinyou

    2014-12-03

    Antibiotic overuse is one of the major drivers in the generation of antibiotic resistant "super bugs" that can potentially cause serious effects on health. In this study, we reported that the polycationic polysaccharide, chitosan could improve the efficacy of a given antibiotic (gentamicin) to combat bacterial biofilms, the universal lifestyle of microbes in the world. Short- or long-term treatment with the mixture of chitosan and gentamicin resulted in the dispersal of Listeria monocytogenes (L. monocytogenes) biofilms. In this combination, chitosan with a moderate molecular mass (~13 kDa) and high N-deacetylation degree (~88% DD) elicited an optimal anti-biofilm and bactericidal activity. Mechanistic insights indicated that chitosan facilitated the entry of gentamicin into the architecture of L. monocytogenes biofilms. Finally, we showed that this combination was also effective in the eradication of biofilms built by two other Listeria species, Listeria welshimeri and Listeria innocua. Thus, our findings pointed out that chitosan supplementation might overcome the resistance of Listeria biofilms to gentamicin, which might be helpful in prevention of gentamicin overuse in case of combating Listeria biofilms when this specific antibiotic was recommended.

  20. Chitosan Improves Anti-Biofilm Efficacy of Gentamicin through Facilitating Antibiotic Penetration

    Directory of Open Access Journals (Sweden)

    Haibo Mu

    2014-12-01

    Full Text Available Antibiotic overuse is one of the major drivers in the generation of antibiotic resistant “super bugs” that can potentially cause serious effects on health. In this study, we reported that the polycationic polysaccharide, chitosan could improve the efficacy of a given antibiotic (gentamicin to combat bacterial biofilms, the universal lifestyle of microbes in the world. Short- or long-term treatment with the mixture of chitosan and gentamicin resulted in the dispersal of Listeria monocytogenes (L. monocytogenes biofilms. In this combination, chitosan with a moderate molecular mass (~13 kDa and high N-deacetylation degree (~88% DD elicited an optimal anti-biofilm and bactericidal activity. Mechanistic insights indicated that chitosan facilitated the entry of gentamicin into the architecture of L. monocytogenes biofilms. Finally, we showed that this combination was also effective in the eradication of biofilms built by two other Listeria species, Listeria welshimeri and Listeria innocua. Thus, our findings pointed out that chitosan supplementation might overcome the resistance of Listeria biofilms to gentamicin, which might be helpful in prevention of gentamicin overuse in case of combating Listeria biofilms when this specific antibiotic was recommended.

  1. Development and validation of an alternative disturbed skin model by mechanical abrasion to study drug penetration

    Directory of Open Access Journals (Sweden)

    P. Schlupp

    2014-01-01

    Skin permeation of the three substances was increased in tape-stripped and abraded skin compared to untreated skin due to the reduced barrier integrity. Enhancement of drug uptake was highest for the most hydrophilic substance, caffeine, followed by sorbic acid and lipophilic testosterone. No significant difference in drug uptake studies was observed between the new abrasion method with an aluminum-coated sponge and the tape-stripping method. The obtained results demonstrate that this abrasion method is an alternative way to achieve a disturbed skin barrier for drug and chemical uptake studies.

  2. Organic Pollutant Penetration through Fruit Polyester Skin: A Modified Three-compartment Diffusion Model

    Science.gov (United States)

    Li, Yungui; Li, Qingqing; Chen, Baoliang

    2016-03-01

    The surface of plants is covered by a continuous but heterogeneous cuticular membrane (CM). Serving as the first protective barrier, the uptake and transport behavior of organic pollutants at this interface continue to engage the research efforts of environmental chemist. To date, the contributions of cuticular components as a defense against the organic pollutants penetration remain unresolved. In this study, the unsteady-state penetration characteristics of phenanthrene (PHE) through isolated fruit CM was investigated. PHE penetration was differentiated by three cuticular compartments: epicuticular waxes (EW), cuticle proper (CP) and cuticular layer (CL). The driving force for PHE penetration was ascribed to the sharp concentration gradient built up endogenously by cuticular compartments with different lipophilic affinities. A modified penetration model was established and verified in terms of its general suitability for the hydrophobic chemicals and CMs of various plant species (apple, tomato and potato). The new three-compartment model demonstrates much higher accuracy in characterizing the uptake and transport behavior of semivolatile chemicals with fewer limitations in terms of environmental conditions and complexity (e.g., coexisting contaminants and temperature). This model could contribute to a more comprehensive understanding on the role of polymeric lipids in the organic pollutant sorption and transport into plants.

  3. Topical delivery of 5-aminolevulinic acid-encapsulated ethosomes in a hyperproliferative skin animal model using the CLSM technique to evaluate the penetration behavior.

    Science.gov (United States)

    Fang, Yi-Ping; Huang, Yaw-Bin; Wu, Pao-Chu; Tsai, Yi-Hung

    2009-11-01

    Psoriasis, an inflammatory skin disease, exhibits recurring itching, soreness, and cracked and bleeding skin. Currently, the topical delivery of 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) is an optional treatment for psoriasis which provides long-term therapeutic effects, is non-toxic and enjoys better compliance with patients. However, the precursor of ALA is hydrophilic, and thus its ability to penetrate the skin is limited. Also, little research has provided a platform to investigate the penetration behavior in disordered skin. We employed a highly potent ethosomal carrier (phosphatidylethanolamine; PE) to investigate the penetration behavior of ALA and the recovery of skin in a hyperproliferative murine model. We found that the application of ethosomes produced a significant increase in cumulative amounts of 5-26-fold in normal and hyperproliferative murine skin samples when compared to an ALA aqueous solution; and the ALA aqueous solution appeared less precise in terms of the penetration mode in hyperproliferative murine skin. After the ethosomes had been applied, the protoporphyrin IX (PpIX) intensity increased about 3.64-fold compared with that of the ALA aqueous solution, and the penetration depth reached 30-80 microm. The results demonstrated that the ethosomal carrier significantly improved the delivery of ALA and the formation of PpIX in both normal and hyperproliferative murine skin samples, and the expression level of tumor necrosis factor (TNF)-alpha was reduced after the ALA-ethosomes were applied to treat hyperproliferative murine skin. Furthermore, the results of present study encourage more investigations on the mechanism of the interaction with ethosomes and hyperproliferative murine skin.

  4. Submicron polymeric particles prepared by vibrational spray-drying: Semisolid formulation and skin penetration/permeation studies.

    Science.gov (United States)

    Beber, T C; Andrade, D F; Kann, B; Fontana, M C; Coradini, K; Windbergs, M; Beck, R C R

    2014-11-01

    Topical glucocorticoids (TG) such as dexamethasone (DEX) have been used for decades for the treatment of skin diseases. However, TG present well-documented side effects and their delivery to the skin is often insufficient. Therefore, many efforts have been undergone to improve the amount of drug delivered to the skin and to reduce side effects at the same time. In this work, the feasibility of DEX-submicron polymeric particles (SP) prepared by vibrational spray-drying as an approach to overcome the challenges associated with the topical administration of this drug class was evaluated. DEX was homogeneously dispersed in the SP matrix, according to confocal Raman microscopy analysis. Drug-loaded SP were incorporated into the oil phase of oil-in-water emulsions (creams). The formulation containing polymeric submicron particles (C-SP) showed controlled drug release kinetics and a significant drug accumulation in skin compared to formulations containing non-polymeric particles or free drug. DEX accumulation in the stratum corneum was evaluated by tape stripping and a depot effect over time was observed for C-SP, while the formulation containing the free drug showed a decrease over time. Similarly, C-SP presented higher drug retention in epidermis and dermis in skin penetration studies performed on pig skin in Franz diffusion cells, while drug permeation into the receptor compartment was negligible. It was demonstrated, for the first time, the advantageous application of submicron polymeric particles obtained by vibrational spray-drying in semisolid formulations for cutaneous administration to overcome challenges related to the therapy with TG such as DEX.

  5. Use of fractional laser microablation and ultrasound to facilitate the delivery of gold nanoparticles into skin in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Terentyuk, G S; Genina, Elina A; Bashkatov, A N; Ryzhova, M V; Tsyganova, N A; Chumakov, D S; Khlebtsov, B N; Sazonov, A A; Dolotov, L E; Tuchin, Valerii V; Khlebtsov, Nikolai G; Inozemtseva, O A

    2012-06-30

    The delivery of gold nanoparticles (nanocages coated with a layer of silicon dioxide (40/20 nm)) dispersed in the solution (glycerol + polyethylene glycol-400, 1 : 1) into the skin tissue is studied experimentally in vivo. From the data of optical coherence tomography and histochemical analysis it follows that simple application of suspension of nanoparticles is not efficient enough for delivery of the particles into the skin as a result of passive diffusion. It is shown that fractional laser microablation of skin before the application of the suspension, followed by the topical treatment by ultrasound allows penetration through the epidermis layer and delivery of nanoparticles into dermis and hypodermis.

  6. Monte Carlo study of skin optical clearing to enhance light penetration in the tissue: implications for photodynamic therapy of acne vulgaris

    Science.gov (United States)

    Bashkatov, Alexey N.; Genina, Elina A.; Tuchin, Valery V.; Altshuler, Gregory B.; Yaroslavsky, Ilya V.

    2008-06-01

    Result of Monte Carlo simulations of skin optical clearing is presented. The model calculations were carried out with the aim of studying of spectral response of skin under immersion liquids action and calculation of enhancement of light penetration depth. In summary, we have shown that: 1) application of glucose, propylene glycol and glycerol produced significant decrease of light scattering in different skin layers; 2) maximal clearing effect will be obtained in case of optical clearing of skin dermis, however, absorbed light fraction in skin dermis changed insignificantly, independently on clearing agent and place it administration; 3) in contrast to it, the light absorbed fraction in skin adipose layer increased significantly in case of optical clearing of skin dermis. It is very important because it can be used for development of optical methods of obesity treatment; 4) optical clearing of superficial skin layers can be used for decreasing of power of light radiation used for treatment of acne vulgaris.

  7. A cyclohexanecarboxamide derivative with inhibitory effects on Schistosoma mansoni cercarial serine protease and penetration of mice skin by the parasite.

    Science.gov (United States)

    Bahgat, Mahmoud; Aboul-Enein, Mohamed N; El Azzouny, Aida A; Maghraby, Amany; Ruppel, Andreas; Soliman, Wael M

    2009-01-01

    A cyclohexanecarboxamide derivative, N-phenyl-N-[1-(piperidine-1-carbonyl)cyclohexyl] benzamide (MNRC-5), was evaluated for its inhibitory effects on Schistosoma mansoni cercarial serine protease activity and cercarial penetration. MNRC-5 exerted an inhibitory effect on S. mansoni cercarial serine protease at serial concentrations of the specific chromogenic substrate Boc-Val-Leu-Gly-Arg-PNA for such enzyme family and the inhibitory coefficient (Ki) value was deduced. Moreover, topical treatment of mice tails with the most potent inhibitory concentration of MNRC-5 formulated in jojoba oil successfully blocked cercarial penetration as demonstrated by a significant reduction (75%; p jojoba oil base containing no MNRC-5. In addition, the IgM and IgG reactivities to crude S. mansoni cercarial, worm and egg antigens were generally lower in sera from treated infected mice than untreated infected mice. In conclusion, we report on a new serine protease inhibitor capable for blocking penetration of host skin by S. mansoni cercariae as measured by lowering worm burden and decrease in the levels of both IgM and IgG towards different bilharzial antigens upon topical treatment.

  8. Penetration profile and human cadaver skin distribution of finasteride from vesicular nanocarriers.

    Science.gov (United States)

    Rao, Yuefeng; Zheng, Feiyue; Liang, Xingguang; Wang, Huiyuan; Zhang, Jin; Lu, Xiaoyang

    2015-12-01

    The skin accumulation of therapeutic agents affects the efficiency of topical drug delivery. In this study, in vitro distribution of finasteride of ethosomes and liposomes in human cadaver skin after percutaneous delivery were investigated. Experiments were performed using modified Franz diffusion cells. Finasteride ethosomes, liposomes or hydroethanolic solutions were used as donor medium. Drug distribution at different skin layers and depths were studied by hotplate separation and frozen horizontal slicing technique. The result showed that the accumulation of finasteride in skin ranged from 9.7-24.3 μg/cm(2) at 12 or 24 hours. The ethosomes demonstrated better enhancing ability to deliver finasteride into the dermis layer than liposomes did. The finasteride concentration in the dermis layer from ethosomes was more than sevenfold higher than from liposomes. The finasteride accumulation in ethosomes group showed a distinctive reversed distribution profile. This distinctive reversed distribution profile is meaningful for exerting a favorable pharmacological effect for finasteride. The drug distribution profile in skin layers showed no significant difference between 12 and 24 hours application (p > 0.05). The study demonstrated that finasteride can be accumulated at target site more effectively and maintained at higher level through the application of novel ethosomal carriers.

  9. Titanium Dioxide Nanoparticle Penetration into the Skin and Effects on HaCaT Cells.

    Science.gov (United States)

    Crosera, Matteo; Prodi, Andrea; Mauro, Marcella; Pelin, Marco; Florio, Chiara; Bellomo, Francesca; Adami, Gianpiero; Apostoli, Pietro; De Palma, Giuseppe; Bovenzi, Massimo; Campanini, Marco; Filon, Francesca Larese

    2015-08-07

    Titanium dioxide nanoparticles (TiO2NPs) suspensions (concentration 1.0 g/L) in synthetic sweat solution were applied on Franz cells for 24 h using intact and needle-abraded human skin. Titanium content into skin and receiving phases was determined. Cytotoxicity (MTT, AlamarBlue(®) and propidium iodide, PI, uptake assays) was evaluated on HaCat keratinocytes after 24 h, 48 h, and seven days of exposure. After 24 h of exposure, no titanium was detectable in receiving solutions for both intact and damaged skin. Titanium was found in the epidermal layer after 24 h of exposure (0.47 ± 0.33 μg/cm(2)) while in the dermal layer, the concentration was below the limit of detection. Damaged skin, in its whole, has shown a similar concentration (0.53 ± 0.26 μg/cm(2)). Cytotoxicity studies on HaCaT cells demonstrated that TiO2NPs induced cytotoxic effects only at very high concentrations, reducing cell viability after seven days of exposure with EC50s of 8.8 × 10(-4) M (MTT assay), 3.8 × 10(-5) M (AlamarBlue(®) assay), and 7.6 × 10(-4) M (PI uptake, index of a necrotic cell death). Our study demonstrated that TiO2NPs cannot permeate intact and damaged skin and can be found only in the stratum corneum and epidermis. Moreover, the low cytotoxic effect observed on human HaCaT keratinocytes suggests that these nano-compounds have a potential toxic effect at the skin level only after long-term exposure.

  10. Titanium Dioxide Nanoparticle Penetration into the Skin and Effects on HaCaT Cells

    Directory of Open Access Journals (Sweden)

    Matteo Crosera

    2015-08-01

    Full Text Available Titanium dioxide nanoparticles (TiO2NPs suspensions (concentration 1.0 g/L in synthetic sweat solution were applied on Franz cells for 24 h using intact and needle-abraded human skin. Titanium content into skin and receiving phases was determined. Cytotoxicity (MTT, AlamarBlue® and propidium iodide, PI, uptake assays was evaluated on HaCat keratinocytes after 24 h, 48 h, and seven days of exposure. After 24 h of exposure, no titanium was detectable in receiving solutions for both intact and damaged skin. Titanium was found in the epidermal layer after 24 h of exposure (0.47 ± 0.33 μg/cm2 while in the dermal layer, the concentration was below the limit of detection. Damaged skin, in its whole, has shown a similar concentration (0.53 ± 0.26 μg/cm2. Cytotoxicity studies on HaCaT cells demonstrated that TiO2NPs induced cytotoxic effects only at very high concentrations, reducing cell viability after seven days of exposure with EC50s of 8.8 × 10−4 M (MTT assay, 3.8 × 10−5 M (AlamarBlue® assay, and 7.6 × 10−4 M (PI uptake, index of a necrotic cell death. Our study demonstrated that TiO2NPs cannot permeate intact and damaged skin and can be found only in the stratum corneum and epidermis. Moreover, the low cytotoxic effect observed on human HaCaT keratinocytes suggests that these nano-compounds have a potential toxic effect at the skin level only after long-term exposure.

  11. Titanium Dioxide Nanoparticle Penetration into the Skin and Effects on HaCaT Cells

    OpenAIRE

    Matteo Crosera; Andrea Prodi; Marcella Mauro; Marco Pelin; Chiara Florio; Francesca Bellomo; Gianpiero Adami; Pietro Apostoli; Giuseppe Palma; Massimo Bovenzi; Marco Campanini; Francesca Larese Filon

    2015-01-01

    Titanium dioxide nanoparticles (TiO2NPs) suspensions (concentration 1.0 g/L) in synthetic sweat solution were applied on Franz cells for 24 h using intact and needle-abraded human skin. Titanium content into skin and receiving phases was determined. Cytotoxicity (MTT, AlamarBlue® and propidium iodide, PI, uptake assays) was evaluated on HaCat keratinocytes after 24 h, 48 h, and seven days of exposure. After 24 h of exposure, no titanium was detectable in receiving solutions for both intact an...

  12. Effect of vehicles and penetration enhancers on the in vitro percutaneous absorption of tenoxicam through hairless mouse skin.

    Science.gov (United States)

    Gwak, Hye Sun; Chun, In Koo

    2002-04-02

    The effects of vehicles and penetration enhancers on the in vitro permeation of tenoxicam from saturated solutions through dorsal hairless mouse skin were investigated. Various types of vehicles, including ester-, alcohol-, and ether-types and their mixtures, were used as vehicles, and then a series of fatty acids and amines were employed as enhancers, respectively. Even though the fluxes of tenoxicam from saturated pure vehicles were generally low (0.1-1.1 microg/cm2 per h), the skin permeability of tenoxicam was significantly increased by the combination of diethylene glycol monoethyl ether (DGME) and propylene glycol monolaurate (PGML) or propylene glycol monocaprylate (PGMC); the highest fluxes were achieved at 40% of DGME in both of the two cosolvents. The marked synergistic enhancement was also obtained by using propylene glycol (PG)-oleyl alcohol (OAl) cosolvent. The greatest flux was attained by the addition of unsaturated fatty acids at 3% concentration to PG. But saturated fatty acids failed to show a significant enhancing effect. The enhancement factors with the addition of oleic acid (OA) or linoleic acid (LOA) to PG were 348 and 238, respectively. Tromethamine (TM) showed an enhancing effect by the increased solubility; however, triethanolamine (TEA) did not show a significant enhancing effect. Rather, it decreased the fluxes of tenoxicam when added to PG with fatty acids. The above results indicate that the combinations of lipophilic vehicles like OA, LOA or OAl and hydrophilic vehicles like PG can be used for enhancing the skin permeation of tenoxicam.

  13. Synergistic efficacy of salicylic acid with a penetration enhancer on human skin monitored by OCT and diffuse reflectance spectroscopy

    Science.gov (United States)

    Zhao, Qingliang; Dai, Cuixia; Fan, Shanhui; Lv, Jing; Nie, Liming

    2016-10-01

    Salicylic acid (SA) has been frequently used as a facial chemical peeling agent (FCPA) in various cosmetics for facial rejuvenation and dermatological treatments in the clinic. However, there is a tradeoff between therapeutic effectiveness and possible adverse effects caused by this agent for cosmetologists. To optimize the cosmetic efficacy with minimal concentration, we proposed a chemical permeation enhancer (CPE) azone to synergistically work with SA on human skin in vivo. The optical properties of human skin after being treated with SA alone and SA combined with azone (SA@azone) were successively investigated by diffuse reflectance spectroscopy (DRS) and optical coherence tomography (OCT). Our results revealed that as the SA concentration increased, the light reflectance decreased and the absorption increased. We also found that SA@azone exhibited a synergistic effect on enhancing light penetration and OCT imaging depth. We demonstrated that the combination of DRS and OCT techniques could be used as a noninvasive, rapid and accurate measurement method to monitor the subtle changes of skin tissue after treatment with FCPA and CPE. The approach will greatly benefit the development of clinical cosmetic surgery, dermatosis diagnosis and therapeutic effect inspection in related biomedical studies.

  14. Synergistic efficacy of salicylic acid with a penetration enhancer on human skin monitored by OCT and diffuse reflectance spectroscopy

    Science.gov (United States)

    Zhao, Qingliang; Dai, Cuixia; Fan, Shanhui; Lv, Jing; Nie, Liming

    2016-01-01

    Salicylic acid (SA) has been frequently used as a facial chemical peeling agent (FCPA) in various cosmetics for facial rejuvenation and dermatological treatments in the clinic. However, there is a tradeoff between therapeutic effectiveness and possible adverse effects caused by this agent for cosmetologists. To optimize the cosmetic efficacy with minimal concentration, we proposed a chemical permeation enhancer (CPE) azone to synergistically work with SA on human skin in vivo. The optical properties of human skin after being treated with SA alone and SA combined with azone (SA@azone) were successively investigated by diffuse reflectance spectroscopy (DRS) and optical coherence tomography (OCT). Our results revealed that as the SA concentration increased, the light reflectance decreased and the absorption increased. We also found that SA@azone exhibited a synergistic effect on enhancing light penetration and OCT imaging depth. We demonstrated that the combination of DRS and OCT techniques could be used as a noninvasive, rapid and accurate measurement method to monitor the subtle changes of skin tissue after treatment with FCPA and CPE. The approach will greatly benefit the development of clinical cosmetic surgery, dermatosis diagnosis and therapeutic effect inspection in related biomedical studies. PMID:27721398

  15. Non-respiratory tuberculosis with Mycobacterium tuberculosis after penetrating lesions of the skin : five case histories

    NARCIS (Netherlands)

    de Jong, JW; van Altena, R

    2000-01-01

    Tuberculosis is primarily transmitted from person to person via the respiratory route. We describe five cases of patients who developed tuberculosis at the site of a skin injury: three after being treated repeatedly with local corticosteroids via intramuscular injections, and two who cut themselves

  16. Non-respiratory tuberculosis with Mycobacterium tuberculosis after penetrating lesions of the skin : five case histories

    NARCIS (Netherlands)

    de Jong, JW; van Altena, R

    2000-01-01

    Tuberculosis is primarily transmitted from person to person via the respiratory route. We describe five cases of patients who developed tuberculosis at the site of a skin injury: three after being treated repeatedly with local corticosteroids via intramuscular injections, and two who cut themselves

  17. Ethosomes - novel vesicular carriers for enhanced delivery: characterization and skin penetration properties.

    Science.gov (United States)

    Touitou, E; Dayan, N; Bergelson, L; Godin, B; Eliaz, M

    2000-04-03

    This work describes a novel carrier for enhanced skin delivery, the ethosomal system, which is composed of phospholipid, ethanol and water. Ethosomal systems were much more efficient at delivering a fluorescent probe to the skin in terms of quantity and depth, than either liposomes or hydroalcoholic solution. The ethosomal system dramatically enhanced the skin permeation of minoxidil in vitro compared with either ethanolic or hydroethanolic solution or phospholipid ethanolic micellar solution of minoxidil. In addition, the transdermal delivery of testosterone from an ethosomal patch was greater both in vitro and in vivo than from commercially available patches. Skin permeation of ethosomal components, ethanol and phospholipid, was demonstrated in diffusion-cell experiments. Ethosomal systems composed of soy phosphatidylcholine 2%, ethanol 30% and water were shown by electron microscopy to contain multilamellar vesicles. 31P-NMR studies confirmed the bilayer configuration of the lipids. Calorimetry and fluorescence measurements suggested that the vesicular bilayers are flexible, having a relatively low T(m) and fluorescence anisotropy compared with liposomes obtained in the absence of ethanol. Dynamic light scattering measurements indicated that ethanol imparted a negative charge to the vesicles. The average vesicle size, as measured by dynamic light scattering, was modulated by altering the ethosome composition. Experiments using fluorescent probes and ultracentrifugation showed that the ethosomes had a high entrapment capacity for molecules of various lyophilicities.

  18. Modelling the Penetration of Salicylates through Skin Using a Silicone Membrane

    Science.gov (United States)

    Wilkins, Andrew; Parmenter, Emily

    2012-01-01

    A diffusion cell to model the permeation of salicylate drugs through the skin using low-cost materials and a sensitive colorimetric analytical technique is described. The diffusion apparatus has been used at a further education college by a student for her AS-level Extended Project to investigate the permeation rates of salicylic acid…

  19. Evaluation of formulation properties and skin penetration in the same additive-containing formulation

    Directory of Open Access Journals (Sweden)

    Yutaka Inoue

    2014-01-01

    Full Text Available The aim of this study is to examine the physicochemical properties of the external preparation, the effect on the skin permeability and the human senses. Miconazole nitrate cream formulation (MCZ-A: bland name and MCZ-B, −C, −D: generics to measure the physicochemical properties, was performed by the skin permeation test and human sensory test. The flattening, viscoelasticity, and water content of each cream were measured and each cream was subjected to near-infrared (NIR absorption spectroscopy and human sensory testing. The yield value was calculated based on measured flattening and was 734.8 dynes/cm2 for MCZ-A, 1198.9 dynes/cm2 for MCZ-B, 461.3 dynes/cm2 for MCZ-C and 3112.3 dynes/cm2 for MCZ-D. Measurement of viscoelasticity and viscosity revealed that MCZ-C had a smaller tanδ than the other 3 creams at 25 °C. NIR absorption spectroscopy revealed that MCZ-A had the highest absorption peak due to hydroxyl groups, followed by MCZ-C, −B, and then −D. Measurement of water content revealed that MCZ-A had a water content of 65.9%, MCZ-B, −C, and −D had a water content of around 56.3%. Human sensory testing revealed differences between MCZ-A and MCZ-C and between MCZ-B and MCZ-D in terms of spreadability and feel. These findings indicate that differences in water and oil content and emulsification resulted in the creams having different physical properties, such as flattening, internal structure, and dynamic viscoelasticity. NIR absorption spectroscopy, which allows non-destructive measurement of a sample’s physicochemical properties, and measurement of viscoelasticity and viscosity, which allows measurement of a sample’s dynamic viscoelasticity, revealed differences in the physical properties of creams. The skin permeation test, skin MCZ amount was 7.48 µg/cm2 for MCZ-A, 5.11 µg/cm2 for MCZ-B, 12.08 µg/cm2 for MCZ-C and 3.75 µg/cm2 for MCZ-D. In addition, since the drug spread is good about the skin migration

  20. Penetration enhancement in mouse skin and lipolysis in adipocytes by TAT-GKH, a new cosmetic ingredient.

    Science.gov (United States)

    Lim, Jun Man; Chang, Min Youl; Park, Sun Gyoo; Kang, Nae Gyu; Song, Young Sook; Lee, Young Hwa; Yoo, Young Chang; Cho, Wan Goo; Choi, Soo Young; Kang, She Hoon

    2003-01-01

    Since the basic domain of human immunodeficiency virus type I (HIV-1) transactivator of transcription (TAT) protein was reported to possess the ability to traverse biological membranes efficiently, various therapeutic proteins have been attached to TAT for the purpose of therapy. In this study, the tripeptide GKH (glycine-lysine-histidine) derived from parathyroid hormone (PTH), known as lipolytic peptide, was attached to 9-poly lysine (TAT) to be used as a cosmetic ingredient in slimming products. TAT-GKH at 10(-5) M induced approximately 37.6% and 41.5% maximal lipolytic effects in cultured 3T3-L1 differentiated adipocytes and in epididymal adipocytes isolated from rats, respectively, compared with basal lipolysis. The lipolytic effect of GKH was not changed by TAT-GKH fusion. In cytotoxicity tests, there was no cytotoxicity in any dose concentration of TAT-GKH. We confirmed that TAT-GKH induced lipolytic activity by GKH without cytotoxicity and with the possibility of its use as a safe cosmetic ingredient. TAT-GKH elevated penetration into excised hairless mice skin 36 times more efficiently than GKH. TAT-GKH can be used as a cosmetic ingredient in slimming products, with both penetration enhancement and lipolytic effect without cytotoxicity.

  1. The isolated blood-perfused pig ear: an inexpensive and animal-saving model for skin penetration studies.

    Science.gov (United States)

    de Lange, J; van Eck, P; Elliott, G R; de Kort, W L; Wolthuis, O L

    1992-04-01

    To overcome most of the disadvantages of current models to investigate percutaneous penetration of drugs or toxic substances, a model is proposed here based on the isolated pig ear, which is obtained at the slaughterhouse, and perfused with oxygenated blood from the same pig. To determine the viability of the preparations, we measured glucose consumption and lactate production as metabolic parameters, Na+ and K+ ions, as well as lactate dehydrogenase activity in blood as markers for cell damage, whereas vasomotor reactivity was assessed by administering noradrenaline and isoxsuprine. After 60 min of equilibration, only insignificant changes in these parameters were observed during the subsequent 3-hr test period (longer periods were not tested). A slight weight increase was noted during the total period 4 hr, presumably due to slight edema formation. On the basis of several types of measurements, such as in vivo blood flow and ear temperature and in vitro glucose metabolism, standard procedures were developed. It is concluded that this technique offers an easy to handle, cost-efficient, and animal-saving model for skin penetration studies that lacks most of the disadvantages of existing models.

  2. Comparison of Franz cells and microdialysis for assessing salicylic acid penetration through human skin.

    Science.gov (United States)

    Leveque, N; Makki, S; Hadgraft, J; Humbert, Ph

    2004-01-28

    The purpose of the present study was to compare Franz cells (FC) and microdialysis (MD) for monitoring the skin absorption of salicylic acid (SA). The influence of pH on SA flux was also assessed by these two techniques. Excised abdominal human skin was used in the experiments. SA was dissolved in phosphate buffer solutions of pH 2, 5 and 7 (2 mg/ml). SA concentrations in the receptor FC solutions and in MD samples were assessed by high performance liquid chromatography (HPLC). The results demonstrate that the flux of SA decreased with increased pH. The profiles permeation determined by Franz cells and microdialysis were similar. However, whatever the pH, the SA flux was higher with microdialysis than with Franz cells. The results showed that SA percutaneous permeation conformed to the pH partition hypothesis. The flux of SA was different when it was determined by the two techniques. The collect of SA, by these two techniques is different. The results of the two techniques are compared and discussed.

  3. Ultra-small lipid nanoparticles promote the penetration of coenzyme Q10 in skin cells and counteract oxidative stress.

    Science.gov (United States)

    Lohan, Silke B; Bauersachs, Sonja; Ahlberg, Sebastian; Baisaeng, Nuttakorn; Keck, Cornelia M; Müller, Rainer H; Witte, Ellen; Wolk, Kerstin; Hackbarth, Steffen; Röder, Beate; Lademann, Jürgen; Meinke, Martina C

    2015-01-01

    UV irradiation leads to the formation of reactive oxygen species (ROS). An imbalance between the antioxidant system and ROS can lead to cell damage, premature skin aging or skin cancer. To counteract these processes, antioxidants such as coenzyme Q10 (CoQ10) are contained in many cosmetics. To improve and optimize cell/tissue penetration properties of the lipophilic CoQ10, ultra-small lipid nanoparticles (usNLC) were developed. The antioxidant effectiveness of CoQ10-loaded usNLC compared to conventional nanocarriers was investigated in the human keratinocyte cell line HaCaT. Using confocal laser scanning microscopy investigations of the carriers additionally loaded with nile red showed a clear uptake into cells and their distribution within the cytoplasm. By use of the XTT cell viability test, CoQ10 concentrations of 10-50 μg/ml were shown to be non-toxic, and the antioxidant potential of 10 μg/ml CoQ10 loaded usNLC in the HaCaT cells was analyzed via electron paramagnetic resonance spectroscopy after cellular exposure to UVA (1J/cm(2)) and UVB (18 mJ/cm(2)) irradiation. In comparison with the CoQ10-loaded conventional carriers, usNLC-CoQ10 demonstrated the strongest reduction of the radical formation; reaching up to 23% compared to control cells without nanocarrier treatment. Therefore, usNLC-CoQ10 are very suitable to increase the antioxidant potential of skin.

  4. Application of Single Molecule Fluorescence Microscopy to Characterize the Penetration of a Large Amphiphilic Molecule in the Stratum Corneum of Human Skin

    Directory of Open Access Journals (Sweden)

    Pierre Volz

    2015-03-01

    Full Text Available We report here on the application of laser-based single molecule total internal reflection fluorescence microscopy (TIRFM to study the penetration of molecules through the skin. Penetration of topically applied drug molecules is often observed to be limited by the size of the respective drug. However, the molecular mechanisms which govern the penetration of molecules through the outermost layer of the skin are still largely unknown. As a model compound we have chosen a larger amphiphilic molecule (fluorescent dye ATTO-Oxa12 with a molecular weight >700 Da that was applied to excised human skin. ATTO-Oxa12 penetrated through the stratum corneum (SC into the viable epidermis as revealed by TIRFM of cryosections. Single particle tracking of ATTO-Oxa12 within SC sheets obtained by tape stripping allowed us to gain information on the localization as well as the lateral diffusion dynamics of these molecules. ATTO-Oxa12 appeared to be highly confined in the SC lipid region between (intercellular space or close to the envelope of the corneocytes. Three main distinct confinement sizes of 52 ± 6, 118 ± 4, and 205 ± 5 nm were determined. We conclude that for this amphiphilic model compound several pathways through the skin exist.

  5. Application of single molecule fluorescence microscopy to characterize the penetration of a large amphiphilic molecule in the stratum corneum of human skin.

    Science.gov (United States)

    Volz, Pierre; Boreham, Alexander; Wolf, Alexander; Kim, Tai-Yang; Balke, Jens; Frombach, Janna; Hadam, Sabrina; Afraz, Zahra; Rancan, Fiorenza; Blume-Peytavi, Ulrike; Vogt, Annika; Alexiev, Ulrike

    2015-03-27

    We report here on the application of laser-based single molecule total internal reflection fluorescence microscopy (TIRFM) to study the penetration of molecules through the skin. Penetration of topically applied drug molecules is often observed to be limited by the size of the respective drug. However, the molecular mechanisms which govern the penetration of molecules through the outermost layer of the skin are still largely unknown. As a model compound we have chosen a larger amphiphilic molecule (fluorescent dye ATTO-Oxa12) with a molecular weight >700 Da that was applied to excised human skin. ATTO-Oxa12 penetrated through the stratum corneum (SC) into the viable epidermis as revealed by TIRFM of cryosections. Single particle tracking of ATTO-Oxa12 within SC sheets obtained by tape stripping allowed us to gain information on the localization as well as the lateral diffusion dynamics of these molecules. ATTO-Oxa12 appeared to be highly confined in the SC lipid region between (intercellular space) or close to the envelope of the corneocytes. Three main distinct confinement sizes of 52 ± 6, 118 ± 4, and 205 ± 5 nm were determined. We conclude that for this amphiphilic model compound several pathways through the skin exist.

  6. Human skin penetration of the major components of Australian tea tree oil applied in its pure form and as a 20% solution in vitro.

    Science.gov (United States)

    Cross, Sheree E; Russell, Michael; Southwell, Ian; Roberts, Michael S

    2008-05-01

    The safety of topical application of Australian tea tree Oil (TTO) is confounded by a lack of transdermal penetration data, which adequately informs opinions and recommendations. In this study we applied TTO in its pure form and as a 20% solution in ethanol in vitro to human epidermal membranes from three different donors, mounted in horizontal Franz-type diffusion cells, using normal 'in use' dosing conditions (10 mg/cm2). In addition, we examined the effect of partially occluding the application site on the penetration of TTO components. Our data showed that only a small quantity of TTO components, 1.1-1.9% and 2-4% of the applied amount following application of a 20% TTO solution and pure TTO, respectively, penetrated into or through human epidermis. The largest TTO component penetrating the skin was terpinen-4-ol. Following partial occlusion of the application site, the penetration of terpinen-4-ol increased to approximately 7% of the applied TTO. Measurement of the rate of evaporation of tea tree oil from filter paper (7.4 mg/cm2) showed that 98% of the oil evaporated in 4 hours. Overall, it is apparent that the penetration of TTO components through human skin is limited.

  7. Skin penetration and deposition of carboxyfluorescein and temoporfin from different lipid vesicular systems: In vitro study with finite and infinite dosage application.

    Science.gov (United States)

    Chen, Ming; Liu, Xiangli; Fahr, Alfred

    2011-04-15

    The aim of the present research is to evaluate the influence of different lipid vesicular systems as well as the effect of application mode on skin penetration and deposition behaviors of carboxyfluorescein (hydrophilic model drug) and temoporfin (lipophilic model drug). All of the lipid vesicular systems, including conventional liposomes, invasomes and ethosomes, were prepared by film hydration method and characterized for particle size distribution, ζ-potential, vesicular shape and surface morphology, in vitro human skin penetration and skin deposition. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) defined that all of lipid vesicles had almost spherical structures with low polydispersity (PDI ethosomes and invasomes, compared with non-vesicular systems, can significantly improve the delivery of hydrophilic drug such as carboxyfluorescein into skin deep layers or across the skin. While in the case of mTHPC with finite and infinite dose application, most of drug accumulation was observed in the skin superficial layer for both lipid vesicular systems and non-vesicular systems. The results also revealed that the factors influencing the drug skin distribution concern the physicochemical characteristics of the drug, the choice of the vehicle formulation and the application mode applied.

  8. Ethosomes for skin delivery of ropivacaine: preparation, characterization and ex vivo penetration properties.

    Science.gov (United States)

    Zhai, Yingjie; Xu, Rui; Wang, Yi; Liu, Jiyong; Wang, Zimin; Zhai, Guangxi

    2015-01-01

    Ropivacaine, a novel long-acting local anesthetic, has been proved to own superior advantage. However, Naropin® Injection, the applied form in clinic, can cause patient non-convenience. The purpose of this study was to formulate ropivacaine (RPV) in ethosomes and evaluate the potential of ethosome formulation in delivering RPV transdermally. The RPV-loaded ethosomes were prepared with thin-film dispersion technique and the formulation was characterized in terms of size, zeta potential, differential scanning calorimetry (DSC) analysis and X-ray diffraction (XRD) study. The results showed that the optimized RPV-ethosomes displayed a typical lipid bilayer structure with a narrow size distribution of 73.86 ± 2.40 nm and drug loading of 8.27 ± 0.37%, EE of 68.92 ± 0.29%. The results of DSC and XRD study indicated that RPV was in amorphous state when encapsulated into ethosomes. Furthermore, the results of ex vivo permeation study proved that RPV-ethosomes could promote the permeability in a high-efficient, rapid way (349.0 ± 11.5 μg cm(-2) at 12 h and 178.8 ± 7.1 μg cm(-2) at 0.5 h). The outcomes of histopathology study forecasted that the interaction between ethosomes and skin could loosen the tight conjugation of corneocyte layers and weaken the permeation barrier. In conclusion, RPV-ethosomes could be a promising delivery system to encapsulate RPV and deliver RPV for transdermal administration.

  9. Radiation formation of functionalized polysaccharide-protein based skin mimicking semi- inter penetrating network for biomedical application.

    Science.gov (United States)

    Singh, Baljit; Kumar, Ajay

    2016-11-01

    Radiation treatment of chitosan, gelatin, polyvinyl alcohol (PVA) and polyacrylamide [poly(AAm)] will form the sterile hydrogel wound dressings which can mimic the artificial skin function in wound therapy. These polymers have been characterized by cryo-scanning electron micrographs (cryo-SEMs), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR) and (13)C solid state nuclear magnetic resonance (NMR) spectroscopy and swelling studies. Some important properties of hydrogel wound dressings like drug delivery, blood compatibility, wound fluid absorption, antioxidant activity, oxygen permeability, water vapour permeability, microbial penetration, mucoadhesion and mechanical properties have also been determined. The release profile of moxifloxacin from the polyacrylamide functionalized chitosan-gelatin matrix followed Fickian diffusion mechanism and release profile best fitted in Korsmeyer-Peppas kinetic model. The hydrogel films are permeable to O2 and H2O vapour and impermeable to microbes in open environment and showed high wound absorption, good mucoadhesion and antioxidant activity. Beside release of antibiotic, the inherent wound healing potential of chitosan, adhesion capacity of gelatin, film forming ability of PVA and wound fluid absorption of poly(AAm), may enhance wound healing potential of these hydrogel wound dressings.

  10. An integral transform approach for a mixed boundary problem involving a flowing partially penetrating well with infinitesimal well skin

    Science.gov (United States)

    Chang, Chien-Chieh; Chen, Chia-Shyun

    2002-06-01

    A flowing partially penetrating well with infinitesimal well skin is a mixed boundary because a Cauchy condition is prescribed along the screen length and a Neumann condition of no flux is stipulated over the remaining unscreened part. An analytical approach based on the integral transform technique is developed to determine the Laplace domain solution for such a mixed boundary problem in a confined aquifer of finite thickness. First, the mixed boundary is changed into a homogeneous Neumann boundary by substituting the Cauchy condition with a Neumann condition in terms of well bore flux that varies along the screen length and is time dependent. Despite the well bore flux being unknown a priori, the modified model containing this homogeneous Neumann boundary can be solved with the Laplace and the finite Fourier cosine transforms. To determine well bore flux, screen length is discretized into a finite number of segments, to which the Cauchy condition is reinstated. This reinstatement also restores the relation between the original model and the solutions obtained. For a given time, the numerical inversion of the Laplace domain solution yields the drawdown distributions, well bore flux, and the well discharge. This analytical approach provides an alternative for dealing with the mixed boundary problems, especially when aquifer thickness is assumed to be finite.

  11. Skin cleaning with kerosene facilitates passage of carcinogens to the lungs of animals treated with used gasoline engine oil.

    Science.gov (United States)

    Lee, J H; Roh, J H; Burks, D; Warshawsky, D; Talaska, G

    2000-04-01

    Solvents such as kerosene or gasoline may be used by workers to clean their skin following contact with oily materials. This practice is not recommended, as it is well known that the solvent will defat the skin. Many also suspect that solvent washing may increase exposure by carrying materials through the skin; however, there is little documentation of this. Auto mechanics may be exposed to used gasoline engine oil (UGEO), an animal carcinogen which forms carcinogen-DNA adducts in skin and lung following topical application. This study was designed to determine if cleaning with kerosene following exposure to UGEO altered absorption of carcinogens from this material. UGEO or new oil (NO) was applied to the shaved skins of groups of HSD-ICR mice for five days. At 1 or 8 hours after application, the treated skins were cleaned with either kerosene or a commercial cleaner, or were not cleaned. Animals were sacrificed 24 hours after the last application, skins and lungs harvested, and DNA analyzed for carcinogen-DNA adducts by 32P-postlabeling. Five applications of UGEO significantly increased carcinogen-DNA adduct levels in both lungs and skin compared to animals treated with NO. DNA adduct levels in the skin were reduced significantly in groups washed with kerosene or commercial cleaner. Washing at one as opposed to eight hours after UGEO application resulted in lower adduct levels regardless of cleaner. DNA adduct levels in the lung were reduced when the commercial cleaner was used, again in a time-related fashion. However, cleaning with kerosene resulted in mean carcinogen-DNA adduct levels in the lung which were significantly higher than even the positive controls, regardless of cleaning time. This is the first demonstration that kerosene cleaning facilitates passage of carcinogens through the skin, resulting in higher levels of genetic damage in a critical internal organ.

  12. Localization of dexamethasone within dendritic core-multishell (CMS) nanoparticles and skin penetration properties studied by multi-frequency electron paramagnetic resonance (EPR) spectroscopy.

    Science.gov (United States)

    Saeidpour, S; Lohan, S B; Anske, M; Unbehauen, M; Fleige, E; Haag, R; Meinke, M C; Bittl, R; Teutloff, C

    2016-10-15

    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.

  13. Molecular profiling reveals diversity of stress signal transduction cascades in highly penetrant Alzheimer's disease human skin fibroblasts.

    Directory of Open Access Journals (Sweden)

    Graziella Mendonsa

    Full Text Available The serious and growing impact of the neurodegenerative disorder Alzheimer's disease (AD as an individual and societal burden raises a number of key questions: Can a blanket test for Alzheimer's disease be devised forecasting long-term risk for acquiring this disorder? Can a unified therapy be devised to forestall the development of AD as well as improve the lot of present sufferers? Inflammatory and oxidative stresses are associated with enhanced risk for AD. Can an AD molecular signature be identified in signaling pathways for communication within and among cells during inflammatory and oxidative stress, suggesting possible biomarkers and therapeutic avenues? We postulated a unique molecular signature of dysfunctional activity profiles in AD-relevant signaling pathways in peripheral tissues, based on a gain of function in G-protein-coupled bradykinin B2 receptor (BKB2R inflammatory stress signaling in skin fibroblasts from AD patients that results in tau protein Ser hyperphosphorylation. Such a signaling profile, routed through both phosphorylation and proteolytic cascades activated by inflammatory and oxidative stresses in highly penetrant familial monogenic forms of AD, could be informative for pathogenesis of the complex multigenic sporadic form of AD. Comparing stimulus-specific cascades of signal transduction revealed a striking diversity of molecular signaling profiles in AD human skin fibroblasts that express endogenous levels of mutant presenilins PS-1 or PS-2 or the Trisomy 21 proteome. AD fibroblasts bearing the PS-1 M146L mutation associated with highly aggressive AD displayed persistent BKB2R signaling plus decreased ERK activation by BK, correctible by gamma-secretase inhibitor Compound E. Lack of these effects in the homologous PS-2 mutant cells indicates specificity of presenilin gamma-secretase catalytic components in BK signaling biology directed toward MAPK activation. Oxidative stress revealed a JNK-dependent survival

  14. 蚊子口针刺入皮肤的刺入力分析%Insertion Force of Mosquito Fascicle Penetrating into Human Skin

    Institute of Scientific and Technical Information of China (English)

    孔祥清; 曲艳东; 章文姣; 吴承伟

    2013-01-01

    A mosquito uses a natural "microneedle" system called fascicle,with a large ratio of the length to the diameter and high flexibility and strength,to painlessly penetrate into human skin and suck blood.The strength of natural "microneedle" system has never problem in the penetrating process.A set of force measurement device with high precision of micro-Newton is designed to measure the insertion force to understand the penetrating process of mosquito fascicle into human skin.The measured results show that the penetrating force of mosquito fascicle into skin is approximately 16μ N.In addition,it has also been found that after the mosquito fascicle tip penetrates into the surface of skin,the force of the mosquito's fascicle penetrating deeper into the skin will decrease as the insertion depth increase,and then levels out at a surprisingly low mean force (even almost be zero).While the insertion force of an artificial needle is 165mN,the force of the artificial needle penetrating deeper into the skin will continue to increase.The study on the insertion mechanism of the mosquito fascicle shows that the mosquito's micronano-structure fascicle and its amazing oscillation inserting skill make it easily penetrate into human skin with a surprising low force.The results are helpful for the optimum design of the microneedles and transdermal drug delivery system.%蚊子能够依靠一个大长径比的高弹性、高强度的天然“微针”——口针无痛地刺入人体皮肤并吸食血液,且刺入过程中从未发生过任何强度问题.本文设计1套高精度微力测量系统对蚊子口针刺入皮肤的刺入力进行在体测量.测量结果表明,蚊子口针刺破皮肤时的刺入力仅约16μN,而且蚊子在进一步的刺入皮肤过程中,口针作用力还将进一步减小并保持在一个极小的值(甚至接近零)附近上下波动,而采用同样实验方案测量的特制人造针头(尖端曲率半径仅约1μm)的刺入力可达165mN,且随

  15. Paclitaxel-loaded lipid nanoparticles for topical application: the influence of oil content on lipid dynamic behavior, stability, and drug skin penetration

    Science.gov (United States)

    Tosta, Fabiana Vaz; Andrade, Lígia Marquez; Mendes, Lívia Palmerston; Anjos, Jorge Luiz V.; Alonso, Antonio; Marreto, Ricardo Neves; Lima, Eliana Martins; Taveira, Stephânia Fleury

    2014-12-01

    Paclitaxel (PAC) has shown potential for regulating hyperkeratosis in skin diseases and its encapsulation in lipid nanoparticles could improve topical treatments. So, solid lipid nanoparticles (SLN) and nanostructured lipid carriers with 12.5 % (NLC1) and 25 % (NLC2) oil content were obtained and characterized. Lipid dynamic behavior was investigated through electron paramagnetic resonance spectroscopy (EPR) and comparative evaluations of EPR, and stability and skin permeation studies were performed. High entrapment efficiency was obtained for all formulations (over 90 %). The absence (SLN) or addition of 12.5 % oil (NLC1) did not significantly alter nanoparticle mean diameter, but 25 % oil (NLC2) produced smaller particles (270.6 ± 13.5 nm). EPR studies showed that 12.5 % oil increased NLC1 fluidity at the surface. Surprisingly, more oil increased NLC2 superficial rigidity, due to the decrease in nanoparticle mean diameter and additional PAC accumulation in the superficial environment. The oil in lipid matrices improved the physicochemical stability of NLC formulations, and drug-oil chemical affinity prevented PAC expulsion during storage time. NLC2 improved PAC skin penetration and was the only formulation capable of enhancing PAC penetration to deeper skin layers (about 6.48 ± 1.39 µg/cm2). PAC-NLC2 seemed to be very promising nanocarriers for the topical delivery of PAC.

  16. Paclitaxel-loaded lipid nanoparticles for topical application: the influence of oil content on lipid dynamic behavior, stability, and drug skin penetration

    Energy Technology Data Exchange (ETDEWEB)

    Tosta, Fabiana Vaz; Andrade, Lígia Marquez; Mendes, Lívia Palmerston [Universidade Federal de Goiás (UFG), Pharmaceutical Technology Laboratory, School of Pharmacy (Brazil); Anjos, Jorge Luiz V. [Universidade Federal de Goiás (UFG), Physics Department (Brazil); Alonso, Antonio [Universidade Federal de Goiás (UFG), Biophysics Laboratory, Physics Institute (Brazil); Marreto, Ricardo Neves; Lima, Eliana Martins; Taveira, Stephânia Fleury, E-mail: stephaniafleury@ufg.br [Universidade Federal de Goiás (UFG), Pharmaceutical Technology Laboratory, School of Pharmacy (Brazil)

    2014-12-15

    Paclitaxel (PAC) has shown potential for regulating hyperkeratosis in skin diseases and its encapsulation in lipid nanoparticles could improve topical treatments. So, solid lipid nanoparticles (SLN) and nanostructured lipid carriers with 12.5 % (NLC1) and 25 % (NLC2) oil content were obtained and characterized. Lipid dynamic behavior was investigated through electron paramagnetic resonance spectroscopy (EPR) and comparative evaluations of EPR, and stability and skin permeation studies were performed. High entrapment efficiency was obtained for all formulations (over 90 %). The absence (SLN) or addition of 12.5 % oil (NLC1) did not significantly alter nanoparticle mean diameter, but 25 % oil (NLC2) produced smaller particles (270.6 ± 13.5 nm). EPR studies showed that 12.5 % oil increased NLC1 fluidity at the surface. Surprisingly, more oil increased NLC2 superficial rigidity, due to the decrease in nanoparticle mean diameter and additional PAC accumulation in the superficial environment. The oil in lipid matrices improved the physicochemical stability of NLC formulations, and drug-oil chemical affinity prevented PAC expulsion during storage time. NLC2 improved PAC skin penetration and was the only formulation capable of enhancing PAC penetration to deeper skin layers (about 6.48 ± 1.39 µg/cm{sup 2}). PAC-NLC2 seemed to be very promising nanocarriers for the topical delivery of PAC.

  17. Ultradeformable lipid vesicles can penetrate the skin and other semi-permeable barriers unfragmented. Evidence from double label CLSM experiments and direct size measurements.

    Science.gov (United States)

    Cevc, Gregor; Schätzlein, Andreas; Richardsen, Holger

    2002-08-19

    The stability of various aggregates in the form of lipid bilayer vesicles was tested by three different methods before and after crossing different semi-permeable barriers. First, polymer membranes with pores significantly smaller than the average aggregate diameter were used as the skin barrier model; dynamic light scattering was employed to monitor vesicle size changes after barrier passage for several lipid mixtures with different bilayer elasticities. This revealed that vesicles must adapt their size and/or shape, dependent on bilayer stability and elasto-mechanics, to overcome an otherwise confining pore. For the mixed lipid aggregates with highly flexible bilayers (Transfersomes), the change is transient and only involves vesicle shape and volume adaptation. The constancy of ultradeformable vesicle size before and after pores penetration proves this. This is remarkable in light of the very strong aggregate deformation during an enforced barrier passage. Simple phosphatidylcholine vesicles, with less flexible bilayers, lack such capability and stability. Conventional liposomes are therefore fractured during transport through a semi-permeable barrier; as reported by other researchers, liposomes are fragmented to the size of a narrow pore if sufficient pressure is applied across the barrier; otherwise, liposomes clog the pores. The precise outcome depends on trans-barrier flux and/or on relative vesicle vs. pore size. Lipid vesicles applied on the skin behave accordingly. Mixed lipid vesicles penetrate the skin if they are sufficiently deformable. If this is the case, they cross inter-cellular constrictions in the organ without significant composition or size modification. To prove this, we labelled vesicles with two different fluorescent markers and applied the suspension on intact murine skin without occlusion. The confocal laser scanning microscopy (CLSM) of the skin then revealed a practically indistinguishable distribution of both labels in the stratum

  18. Improvement in UV protection retention capability and reduction in skin penetration of benzophenone-3 with mesoporous silica as drug carrier by encapsulation.

    Science.gov (United States)

    Li, C C; Lin, Y T; Chen, Y T; Sie, S F; Chen-Yang, Y W

    2015-07-01

    In this study, various amounts of benzophenone-3 (BP-3), a solid-type of organic UV-filter, were encapsulated in mesoporous silica (MS) to form the BP-3 encapsulated by MS UV-filters (BESs), BES-1 and BES-2, via in-situ sol-gel process. The characterization of BESs was completed using Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The results showed that of the BES filters, BES-2 containing emulsion (BES-2-E) exhibited about 2 times and 1.64 times higher SPF and erythemal UV-A PF values, respectively, and after 3 months about 7-8 times higher protection retention capability than the free BP-3 containing emulsion (BP-3-E). Moreover, the result of the in vitro skin penetration test using Franz glass diffusion cell indicated that the skin permeation of BP-3 from BESs was about 3 times lower than from BP-3-E. This property is particularly important for sunscreens because the amount of sunscreen penetration inside the stratum corneum directly correlates to its UV protection ability, and consequently its ability to reduce phototoxic and photo-allergic reactions that are damaging to the skin. The results of this study demonstrated the potential of as-prepared BES-2 as a UV-filter for cosmetic products.

  19. Effects of Sizes and Conformations of Fish-Scale Collagen Peptides on Facial Skin Qualities and Transdermal Penetration Efficiency

    Directory of Open Access Journals (Sweden)

    Huey-Jine Chai

    2010-01-01

    Full Text Available Fish-scale collagen peptides (FSCPs were prepared using a given combination of proteases to hydrolyze tilapia (Oreochromis sp. scales. FSCPs were determined to stimulate fibroblast cells proliferation and procollagen synthesis in a time- and dose-dependent manner. The transdermal penetration capabilities of the fractionationed FSCPs were evaluated using the Franz-type diffusion cell model. The heavier FSCPs, 3500 and 4500 Da, showed higher cumulative penetration capability as opposed to the lighter FSCPs, 2000 and 1300 Da. In addition, the heavier seemed to preserve favorable coiled structures comparing to the lighter that presents mainly as linear under confocal scanning laser microscopy. FSCPs, particularly the heavier, were concluded to efficiently penetrate stratum corneum to epidermis and dermis, activate fibroblasts, and accelerate collagen synthesis. The heavier outweighs the lighter in transdermal penetration likely as a result of preserving the given desired structure feature.

  20. Hair follicle targeting, penetration enhancement and Langerhans cell activation make cyanoacrylate skin surface stripping a promising delivery technique for transcutaneous immunization with large molecules and particle-based vaccines.

    Science.gov (United States)

    Vogt, Annika; Hadam, Sabrina; Deckert, Iliane; Schmidt, Julia; Stroux, Andrea; Afraz, Zahra; Rancan, Fiorenza; Lademann, Jürgen; Combadiere, Behazine; Blume-Peytavi, Ulrike

    2015-01-01

    Transcutaneous immunization (TCI) requires targeting of a maximum number of skin antigen-presenting cells as non-invasive as possible on small skin areas. In two clinical trials, we introduced cyanoacrylate skin surface stripping (CSSS) as a safe method for TCI. Here, using ex vivo human skin, we demonstrate that one CSSS procedure removed only 30% of stratum corneum, but significantly increased the penetration of 200 nm polystyrene particles deep into vellus and intermediate hair follicles from where they could not been retrieved by conventional tape stripping. Two subsequent CSSS had no striking additional effect. CSSS increased particle penetration in superficial stratum corneum and induced Langerhans cell activation. Formulation in amphiphilic ointment or massage did not substantially influences the interfollicular penetration profiles. Hair follicle (HF) targeting by CSSS could become a highly effective tool for TCI when combined with carrier-based delivery and is gaining new attention as our understanding on the HF immune system increases.

  1. Development of an in vivo animal model for skin penetration in hairless rats assessed by mass balance

    DEFF Research Database (Denmark)

    Simonsen, Lene; Petersen, Mads B; Benfeldt, Eva

    2002-01-01

    acid and (14)C-butyl salicylate were topically applied. Rapid and differentiated percutaneous absorption of both compounds were shown by urinary excretion data. For (14)C-salicylic acid the amount on the skin surface, in the stratum corneum and in the viable skin was determined. Total mass balance...... rat and free mobility throughout the test period. By consecutive tape stripping, monitored by measurements of transepidermal water loss and confirmed by histological examination of skin biopsies, 10 tape strippings were found to remove the stratum corneum completely. For assessment of the model, (14)C-salicylic...

  2. A validated HPLC analytical method for the analysis of solasonine and solamargine in in vitro skin penetration studies

    Directory of Open Access Journals (Sweden)

    Renata F. J. Tiossi

    2012-01-01

    Full Text Available To assess topical delivery studies of glycoalkaloids, an analytical method by HPLC-UV was developed and validated for the determination of solasonine (SN and solamargine (SM in different skin layers, as well as in a topical formulation. The method was linear within the ranges 0.86 to 990.00 µg/mL for SN and 1.74 to 1000.00 µg/mL for SM (r = 0.9996. Moreover, the recoveries for both glycoalkaloids were higher than 88.94 and 93.23% from skin samples and topical formulation, respectively. The method developed is reliable and suitable for topical delivery skin studies and for determining the content of SN and SM in topical formulations.

  3. Development of an in vivo animal model for skin penetration in hairless rats assessed by mass balance

    DEFF Research Database (Denmark)

    Simonsen, Lene; Petersen, Mads B; Benfeldt, Eva

    2002-01-01

    rat and free mobility throughout the test period. By consecutive tape stripping, monitored by measurements of transepidermal water loss and confirmed by histological examination of skin biopsies, 10 tape strippings were found to remove the stratum corneum completely. For assessment of the model, (14)C...

  4. Skin Penetration Study of Nanotopes Uitra- Small Carrier System%纳能托[注]超微载体系统的透皮性能研究

    Institute of Scientific and Technical Information of China (English)

    张贵民

    2001-01-01

    This paper studied the in- vitro viable skin penetration of 2 % ( w/% ) vitamin E acetate in Nanotopes ultra- small carrier system, small liposomes and caprylic/capric triglyceride solution respectively. Total vitamin E and free vitamin E in different depth of the skin was measured quantitatively. The experiments carried out on modified Franz diffusion cell by using viable human skin obtained from hospitals in Munchen, Germany within 2 of surgical operation indicated that with its ultra - small particle size ( av. d < 30nm) and compact single lecithin layer structure, Nanotopes loaded with vitamin E acetate- Tinederm E can effectively pass stratum corneum (the homy layer) of human skin thus carries the active into epidermis, dennis, subcutis and up to fat layers as deep as 1, 250 μm from skin surface. The vitamin E acetate transported into viable skin by the Nanotope system was then converted into free vitamin E (tocopherol) by enzymes in the skin. It is proved that only by releasing or hydrolyzed into free vitamin E or tocopherol can ritamin E acetate act as an effective antioxidant and free radical scavenger as well as providing good cell nutrition.%研究了质量分数为2%维生素E醋酸酯分别在纳能托[注]超微载体系统、超小脂质体系统以及辛酸/癸酸甘油三酯溶液中的体外活皮肤渗透性能。精确测定了皮肤不同深度层面区间中总维生素E以及纯维生素E的含量。研究发现:含有维生素E醋酸酯的纳能托[注]超微载体一天来达[注]E能够以其超小的体积(d平均<30nm)和紧密的结构有效通过人体皮肤的角质层屏障到达表皮层、真皮层、皮下组织以及深达1 250μm的皮肤脂肪层,并能够在皮肤中活性酶的作用下大量转化成为具有活性的纯维生素E(即维生素E醇),从而有效营养皮肤,防止皮肤细胞质的氧化及紫外线引起的自由基老化等。

  5. Identification and partial sequencing of a crocodile poxvirus associated with deeply penetrating skin lesions in farmed Nile crocodiles, Crocodylus niloticus.

    Science.gov (United States)

    Huchzermeyer, F W; Wallace, D B; Putterill, J F; Gerdes, G H

    2009-09-01

    When large numbers of crocodile skins were downgraded because of the presence of small pin prick-like holes, collapsed epidermal cysts were found deep in the dermis of juvenile crocodiles while forming cysts were observed in hatchlings. Histopathology of these forming cysts showed the presence of intracytoplasmic inclusions in proliferating and ballooning epidermal cells. Pox virions were seen in electron microscope preparations made from the scabs of such early lesions. The partial sequencing of virus material from scrapings of these lesions and comparison of it with the published sequence of crocodile poxvirus showed the virus associated with the deep lesions to be closely related, but different. To differentiate between the two forms of crocodile pox infection it is suggested that the previously known form should be called "classical crocodile pox" and the newly discovered form "atypical crocodile pox". The application of strict hygiene measures brought about a decline in the percentage of downgraded skins.

  6. Identification and partial sequencing of a crocodile poxvirus associated with deeply penetrating skin lesions in farmed Nile crocodiles, Crocodylus niloticus

    Directory of Open Access Journals (Sweden)

    F.W. Huchzermeyer

    2009-09-01

    Full Text Available When large numbers of crocodile skins were downgraded because of the presence of small pin pricklike holes, collapsed epidermal cysts were found deep in the dermis of juvenile crocodiles while forming cysts were observed in hatchlings. Histopathology of these forming cysts showed the presence of intracytoplasmic inclusions in proliferating and ballooning epidermal cells. Pox virions were seen in electron microscope preparations made from the scabs of such early lesions. The partial sequencing of virus material from scrapings of these lesions and comparison of it with the published sequence of crocodile poxvirus showed the virus associated with the deep lesions to be closely related, but different. To differentiate between the two forms of crocodile pox infection it is suggested that the previously known form should be called ''classical crocodile pox'' and the newly discovered form ''atypical crocodile pox''. The application of strict hygiene measures brought about a decline in the percentage of downgraded skins.

  7. Role of the charge, carbon chain length, and content of surfactant on the skin penetration of meloxicam-loaded liposomes

    Directory of Open Access Journals (Sweden)

    Duangjit S

    2014-04-01

    Full Text Available Sureewan Duangjit,1,2 Boonnada Pamornpathomkul,1 Praneet Opanasopit,1 Theerasak Rojanarata,1 Yasuko Obata,2 Kozo Takayama,2 Tanasait Ngawhirunpat11Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand; 2Department of Pharmaceutics, Hoshi University, Shinagawa-ku, Tokyo, JapanAbstract: The objective of this study was to investigate the influence of surfactant charge, surfactant carbon chain length, and surfactant content on the physicochemical characteristics (ie, vesicle size, zeta potential, elasticity, and entrapment efficiency, morphology, stability, and in vitro skin permeability of meloxicam (MX-loaded liposome. Moreover, the mechanism for the liposome-enhanced skin permeation of MX was determined by Fourier transform infrared spectroscopy and differential scanning calorimetry. The model formulation used in this study was obtained using a response surface method incorporating multivariate spline interpolation (RSM-S. Liposome formulations with varying surfactant charge (anionic, neutral, and cationic, surfactant carbon chain length (C4, C12, and C16, and surfactant content (10%, 20%, and 29% were prepared. The formulation comprising 29% cationic surfactant with a C16 chain length was found to be the optimal liposome for the transdermal delivery of MX. The skin permeation flux of the optimal formulation was 2.69-fold higher than that of a conventional liposome formulation. Our study revealed that surfactants affected the physicochemical characteristics, stability, and skin permeability of MX-loaded liposomes. These findings provide important fundamental information for the development of liposomes as transdermal drug delivery systems.Keywords: optimal liposome, optimization, transdermal drug delivery, surfactant charge, surfactant carbon chain length, surfactant content

  8. Investigating the ability of nanoparticle-loaded hydroxypropyl methylcellulose and xanthan gum gels to enhance drug penetration into the skin.

    Science.gov (United States)

    Cai, X J; Mesquida, P; Jones, S A

    2016-11-20

    Nanoparticle-loaded topical formulations can disrupt drug aggregation through controlled drug-nanoparticle interactions to enhance topical drug delivery. However, the complex relationship between the drug, nanoparticle and formulation vehicle requires further understanding. The aim of this study was to use nanoparticle-loaded hydroxypropyl methylcellulose (HPMC) and xanthan gum gels to probe how the drug, nanoparticle and formulation vehicle interactions influenced the delivery of an aggregated drug into the skin. Tetracaine was chosen as a model drug. It was loaded into HPMC and xanthan gum gels, and it was presented to porcine skin using infinite and finite dosing protocols. Gel infinite doses showed no important differences in tetracaine skin permeation rate, but HPMC gel finite doses delivered the drug more efficiently (46.99±7.96μg/cm(2)/h) compared to the xanthan gum (1.16±0.14μg/cm(2)/h). Finite doses of the nanoparticle-loaded HPMC gel generated a 10-fold increase in drug flux (109.95±28.63μg/cm(2)/h) compared to the equivalent xanthan gum system (14.19±2.27μg/cm(2)/h). Rheology measurements suggested that the differences in the gels ability to administer the drug into the skin were not a consequence of gel-nanoparticle interactions rather, they were a consequence of the dehydration mediated diffusional restriction imparted on the drug by xanthan gum compared to the viscosity independent interactions of HPMC with the drug.

  9. Improved Skin Penetration Using In Situ Nanoparticulate Diclofenac Diethylamine in Hydrogel Systems: In Vitro and In Vivo Studies.

    Science.gov (United States)

    Sengupta, Soma; Banerjee, Sarita; Sinha, Biswadip; Mukherjee, Biswajit

    2016-04-01

    Delivering diclofenac diethylamine transdermally by means of a hydrogel is an approach to reduce or avoid systemic toxicity of the drug while providing local action for a prolonged period. In the present investigation, a process was developed to produce nanosize particles (about 10 nm) of diclofenac diethylamine in situ during the development of hydrogel, using simple mixing technique. Hydrogel was developed with polyvinyl alcohol (PVA) (5.8% w/w) and carbopol 71G (1.5% w/w). The formulations were evaluated on the basis of field emission scanning electron microscopy, texture analysis, and the assessment of various physiochemical properties. Viscosity (163-165 cps for hydrogel containing microsize drug particles and 171-173 cps for hydrogel containing nanosize drug particles, respectively) and swelling index (varied between 0.62 and 0.68) data favor the hydrogels for satisfactory topical applications. The measured hardness of the different hydrogels was uniform indicating a uniform spreadability. Data of in vitro skin (cadaver) permeation for 10 h showed that the enhancement ratios of the flux of the formulation containing nanosize drug (without the permeation enhancer) were 9.72 and 1.30 compared to the formulation containing microsized drug and the marketed formulations, respectively. In vivo plasma level of the drug increased predominantly for the hydrogel containing nanosize drug-clusters. The study depicts a simple technique for preparing hydrogel containing nanosize diclofenac diethylamine particles in situ, which can be commercially viable. The study also shows the advantage of the experimental transdermal hydrogel with nanosize drug particles over the hydrogel with microsize drug particles.

  10. Human lung fibroblast-derived matrix facilitates vascular morphogenesis in 3D environment and enhances skin wound healing.

    Science.gov (United States)

    Du, Ping; Suhaeri, Muhammad; Ha, Sang Su; Oh, Seung Ja; Kim, Sang-Heon; Park, Kwideok

    2017-05-01

    challenging due to the difficulty of recapitulating the complex angiogenic extracellular matrix (ECM) environment. Herein, we present a simple and practical method to create an angiogenic 3D environment via incorporation of human lung fibroblast-derived matrix (hFDM) into collagen hydrogel. We found that hFDM offers a significantly improved angiogenic microenvironment for HUVECs on 2D substrates and in 3D construct. A synergistic effect of hFDM and angiogenic growth factors has been well confirmed in 3D condition. The prevascularized 3D collagen constructs also facilitate skin wound healing. We believe that current system should be a convenient and powerful platform in engineering 3D vasculature in vitro, and in delivering cells for therapeutic purposes in vivo. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  11. Antimicrobial and anti-thrombogenic features combined in hydrophilic surface coatings for skin-penetrating catheters. Synergy of co-embedded silver particles and heparin.

    Science.gov (United States)

    Croes, Sander; Stobberingh, Ellen E; Stevens, Kris N J; Knetsch, Menno L W; Koole, Leo H

    2011-07-01

    Percutaneous (skin-penetrating) catheters such as central venous catheters (CVCs), are used ubiquitously in the treatment of critically ill patients, although it is known that the risks for serious complications, particularly bloodstream infection and thromboembolism, are high. Materials science and engineering offer important new perspectives regarding further improvement of CVCs. A promising approach is the use of synthetic biocompatible hydrogel coatings with both silver particles and heparin embedded therein. Such formulations combine the well-known broad-spectrum antimicrobial features of silver with the anticoagulant activity of immobilized heparin. Previous work revealed that heparin augments antimicrobial activity of silver, while maintaining its anticoagulant function. This study set out to investigate the synergy of heparin and silver in more detail. Exit-challenge tests, experiments on bacterial killing and adherence, as well as in vitro challenge tests with three Staphylococcus aureus strains (one reference strain, and two clinical isolates) consistently showed the synergistic effect. In addition, the impact of changing the coating's hydrophilicity, and changing the silver concentration in the coatings, were examined. The experimental results, taken together and combined with data from the literature, point out that synergy of heparin and silver is best explained by binding of Ag(+) ions to heparin within the swollen coating, followed by release of heparin-Ag(+) complexes upon immersion of the coatings in an aqueous environment such as blood. Possible implications of this work regarding the development of improved/safer CVCs are briefly discussed.

  12. Cleansing Formulations That Respect Skin Barrier Integrity

    Directory of Open Access Journals (Sweden)

    Russel M. Walters

    2012-01-01

    Full Text Available Surfactants in skin cleansers interact with the skin in several manners. In addition to the desired benefit of providing skin hygiene, surfactants also extract skin components during cleansing and remain in the stratum corneum (SC after rinsing. These side effects disrupt SC structure and degrade its barrier properties. Recent applications of vibrational spectroscopy and two-photon microscopy in skin research have provided molecular-level information to facilitate our understanding of the interaction between skin and surfactant. In the arena of commercial skin cleansers, technologies have been developed to produce cleansers that both cleanse and respect skin barrier. The main approach is to minimize surfactant interaction with skin through altering its solution properties. Recently, hydrophobically modified polymers (HMPs have been introduced to create skin compatible cleansing systems. At the presence of HMP, surfactants assemble into larger, more stable structures. These structures are less likely to penetrate the skin, thereby resulting in less aggressive cleansers and the integrity of the skin barrier is maintained. In this paper, we reviewed our recent findings on surfactant and SC interactions at molecular level and provided an overview of the HM technology for developing cleansers that respect skin barrier.

  13. [Comments on the paper by D. Tausch et al. Experiments on the penetration power of various bullets into skin and muscle tissue (author's transl)].

    Science.gov (United States)

    Dammermann, W

    1979-07-17

    The objections in the following comments on a recent paper by Tausch et al. (1978) are raised principally to the points that the mass of the projectile is given an importance for the penetration which is not justified, and that the inherent uncertainty of the measurement data and the scope of validity of the empirical formulas are not sufficiently taken into account. The discussion on the process of penetration and a discontinuity of the depth of penetration as a function of the velocity of the bullet is of fundamental significance, with consequences for the definition of the critical velocity.

  14. Controlled Penetration of a Novel Dimeric Ceramide into and across the Stratum Corneum Using Microemulsions and Various Types of Semisolid Formulations.

    Science.gov (United States)

    Neubert, Reinhard H H; Sonnenberger, Stefan; Dobner, Bodo; Gray, Charles W; Barger, K Natalie; Sevi-Maxwell, Kara; Sommer, Elfi; Wohlrab, Johannes

    2016-01-01

    Ceramides (CERs) are integral parts of the intercellular lipid lamellae of the stratum corneum (SC), which is responsible for the barrier function of the skin. Many skin diseases such as atopic dermatitis and psoriasis are associated with the depletion or disturbance of the level of CERs in the SC. Administration of an exogenous novel dimeric ceramide (dCER) deep into the SC may help to stabilize the SC barrier substantially and to treat some skin disease conditions. Consequently, with the help of the existing technology, it might be possible to formulate various pharmaceutical dosage forms that can facilitate penetration of dCER into the SC. Therefore, the penetration of dCER was studied using a high-performance liquid chromatography/atmospheric-pressure ionization/mass spectrometry method for the detection and quantification of exogenous dCER in the SC as well as other skin layers. Penetration studies were carried out in the Franz diffusion cell using excised human skin ex vivo. Penetration of dCER was studied with 3 model formulations: a colloidal formulation (microemulsion), a cream formulation with ethoxydiglycol as penetration enhancer and a nanoformulation. The highest concentrations of dCER in the different skin layers were found after application of the cream with penetration enhancer. Surprisingly, the lowest concentrations of dCER in the different skin layers were found after application of the microemulsion. © 2016 S. Karger AG, Basel.

  15. 苦鲜湿疹凝胶剂的制备及体外渗透性%Preparation of Kuxian eczema gel and its skin penetration properties in vitro

    Institute of Scientific and Technical Information of China (English)

    吕立华; 张玉碧; 杨蓝

    2011-01-01

    目的:研究苦鲜湿疹凝胶剂的制备及其体外渗透性.方法:羟丙基甲基纤维素(HPMC)和聚乙烯吡咯烷酮(PVP)为基质,制备苦鲜湿疹凝胶剂.采用改良Franz扩散池,以离体小鼠皮肤为透皮屏障,用HPLC法测定苦参碱的累积渗透量.结果:090416:Y2=614.95X2-463.75,r2=0.9939,090423:Y2=601.41X2-426.32,r'2=0.996 9,080428:Y2=635.90X2-481.08,r2''=0.997 8,经皮渗透过程符合Higuchi方程(r=0.998).结论:苦鲜湿疹凝胶剂中的苦参碱以Higuchi动力学经皮渗透.%OBJECTIVE To prepare Kuxian eczema gel and to study the skin penetration in vitro. METHODS Kuxian eczema gel was prepared with Carbomer-940, hydroxypropyl methylcellulose( HPMC)and polyvinylpyrrolidone(PVP) as base materials. Using improved Franz-type diffusion cell and isolated mice skin as transdermal barrine, the cumulative permeation quantity of matrine was determined by HPLC method. RESULTS 090416:Y2 = 614. 95X2 - 463. 75,r2 = 0. 993 9, 090423:Y2' = 601.41 X2 - 426. 32, r2' = 0. 996 9, 080428: Y2" = 635. 90X2 - 481.08, r2" = 0. 997 8, The penetration equation of matrine in eczema gel was Higuchi (r= 0. 998). CONCLUSION The penetration of matrine of Kuxian eczema gel through the mice skin follows Higuchi kinetics.

  16. Investigation of the cutaneous penetration behavior of dexamethasone loaded to nano-sized lipid particles by EPR spectroscopy, and confocal Raman and laser scanning microscopy.

    Science.gov (United States)

    Lohan, Silke B; Saeidpour, Siavash; Solik, Agnieszka; Schanzer, Sabine; Richter, Heike; Dong, Pin; Darvin, Maxim E; Bodmeier, Roland; Patzelt, Alexa; Zoubari, Gaith; Unbehauen, Michael; Haag, Rainer; Lademann, Jürgen; Teutloff, Christian; Bittl, Robert; Meinke, Martina C

    2017-07-01

    An improvement of the penetration efficiency combined with the controlled release of actives in the skin can facilitate the medical treatment of skin diseases immensely. Dexamethasone (Dx), a synthetic glucocorticoid, is frequently used for the treatment of inflammatory skin diseases. To investigate the penetration of nano-sized lipid particles (NLP) loaded with Dx in comparison to a commercially available base cream, different techniques were applied. Electron paramagnetic resonance (EPR) spectroscopy was used to monitor the penetration of Dx, which was covalently labeled with the spin probe 3-(Carboxy)-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (PCA). The penetration into hair follicles was studied using confocal laser scanning microscopy (CLSM) with curcumin-loaded NLP. The penetration of the vehicle was followed by confocal Raman microscopy (CRM). Penetration studies using excised porcine skin revealed a more than twofold higher penetration efficiency for DxPCA into the stratum corneum (SC) after 24h incubation compared to 4h incubation when loaded to the NLP, whereas when applied in the base cream, almost no further penetration was observed beyond 4h. The distribution of DxPCA within the SC was investigated by consecutive tape stripping. The release of DxPCA from the base cream after 24h in deeper SC layers and the viable epidermis was shown by EPR. For NLP, no release from the carrier was observed, although DxPCA was detectable in the skin after the complete SC was removed. This phenomenon can be explained by the penetration of the NLP into the hair follicles. However, penetration profiles measured by CRM indicate that NLP did not penetrate as deeply into the SC as the base cream formulation. In conclusion, NLP can improve the accumulation of Dx in the skin and provide a reservoir within the SC and in the follicular infundibula. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Skin penetration and metabolism of topically applied chemicals in six mammalian species, including man: an in vitro study with benzo(a)pyrene and testosterone

    Energy Technology Data Exchange (ETDEWEB)

    Kao, J.; Patterson, F.K.; Hall, J.

    1985-12-01

    Because viable skin possesses enzyme activities, including those involved in the metabolism of xenobiotics, the extent to which cutaneous metabolism may influence the percutaneous fate of topically applied chemicals in the skin was examined in mammalian skin maintained as short-term organ cultures. Skin samples from mouse, rat, rabbit, guinea pig, marmoset, and man were examined. The results from studies with benzo(a)pyrene (BP) and testosterone showed that, in all species, metabolic viability was a major factor involved in the in vitro skin permeation of surface-applied chemicals. Permeation was accompanied by extensive cutaneous first pass metabolism; both parent compounds and a full spectrum of metabolites were found in the receptor fluid from viable skin preparations. However, in previously frozen nonviable skin preparations, essentially only unchanged parent compounds were detected in the receptor fluid. Permeation of BP and testosterone was highest in mouse skin, and significant species variations in the metabolite profiles were observed. Studies with mouse skin also demonstrated that induction of cutaneous drug-metabolizing enzymes can result in a two- to threefold increase in the in vitro permeation of topical BP, and a significant reduction in permeation was observed when KCN was added to the perfusion medium. These results indicate that diffusional and metabolic processes are intimately involved in the percutaneous fate of surface-applied chemicals. The relative importance of these processes is dependent upon the physicochemical properties of the compounds and the metabolic capabilities of the skin toward the compounds in question. Furthermore, these findings suggest that meaningful in vitro studies on skin absorption should consider both diffusion and cutaneous biotransformation of the applied compound.

  18. Penetration equations

    Energy Technology Data Exchange (ETDEWEB)

    Young, C.W. [Applied Research Associates, Inc., Albuquerque, NM (United States)

    1997-10-01

    In 1967, Sandia National Laboratories published empirical equations to predict penetration into natural earth materials and concrete. Since that time there have been several small changes to the basic equations, and several more additions to the overall technique for predicting penetration into soil, rock, concrete, ice, and frozen soil. The most recent update to the equations was published in 1988, and since that time there have been changes in the equations to better match the expanding data base, especially in concrete penetration. This is a standalone report documenting the latest version of the Young/Sandia penetration equations and related analytical techniques to predict penetration into natural earth materials and concrete. 11 refs., 6 tabs.

  19. Biodegradable Gelatin Microcarriers Facilitate Re-Epithelialization of Human Cutaneous Wounds - An In Vitro Study in Human Skin.

    Science.gov (United States)

    Lönnqvist, Susanna; Rakar, Jonathan; Briheim, Kristina; Kratz, Gunnar

    2015-01-01

    The possibility to use a suspended tridimensional matrix as scaffolding for re-epithelialization of in vitro cutaneous wounds was investigated with the aid of a human in vitro wound healing model based on viable full thickness skin. Macroporous gelatin microcarriers, CultiSpher-S, were applied to in vitro wounds and cultured for 21 days. Tissue sections showed incorporation of wound edge keratinocytes into the microcarriers and thicker neoepidermis in wounds treated with microcarriers. Thickness of the neoepidermis was measured digitally, using immunohistochemical staining of keratins as epithelial demarcation. Air-lifting of wounds enhanced stratification in control wounds as well as wounds with CultiSpher-S. Immunohistochemical staining revealed expression of keratin 5, keratin 10, and laminin 5 in the neoepidermal component. We conclude that the CultiSpher-S microcarriers can function as tissue guiding scaffold for re-epithelialization of cutaneous wounds.

  20. Development of a stratum corneum substitute for in vitro percutaneous penetration studies : a skin barrier model comprising synthetic stratum corneum lipids

    NARCIS (Netherlands)

    Jager, Miranda Wilhelmina de

    2006-01-01

    The research outlined in this thesis was focused on the development of a skin barrier model, which can substitute for stratum corneum in diffusion studies. This so-called stratum corneum substitute (SCS) was prepared with reconstituted SC lipids (cholesterol, free fatty acids and ceramides) on a por

  1. Development of a stratum corneum substitute for in vitro percutaneous penetration studies : a skin barrier model comprising synthetic stratum corneum lipids

    NARCIS (Netherlands)

    Jager, Miranda Wilhelmina de

    2006-01-01

    The research outlined in this thesis was focused on the development of a skin barrier model, which can substitute for stratum corneum in diffusion studies. This so-called stratum corneum substitute (SCS) was prepared with reconstituted SC lipids (cholesterol, free fatty acids and ceramides) on a

  2. Penetration-enhancing effect of ethanol-water solvent system and ethanolic solution of carvone on transdermal permeability of nimodipine from HPMC gel across rat abdominal skin.

    Science.gov (United States)

    Krishnaiah, Y S R; Bhaskar, P; Satyanarayana, V

    2004-01-01

    The aim of this investigation was to find the effect of the ethanol-water solvent system and the ethanolic solution of carvone on the permeation of nimodipine across rat abdominal skin in order to select a suitable solvent system and optimal concentration of carvone for the development of membrane-moderated transdermal therapeutic system of nimodipine. The solubility of nimodipine in water, ethanol, and ethanol-water cosolvent systems, or the selected concentration of carvone [2% (w/w) to 12% (w/w)] in 60:40 (v/v) ethanol-water were determined. The effect of these solvents or cosolvent systems on the transdermal permeation of nimodipine was also studied using in vitro permeability studies across the rat abdominal skin. The co-solvent system containing 60:40 (v/v) of ethanol-water showed highest permeability across the rat abdominal skin. Further, the effect of ethanolic solution [60% (v/v) ethanol-water] of carvone [2% (w/w) to 12% (w/w)] on the in vitro permeation of nimodipine across the rat abdominal skin from 2% (w/w) hydroxypropyl methylcellulose (HPMC) gel was also investigated. The transdermal permeability of nimodipine across rat abdominal skin was enhanced further by the addition of carvone to HPMC gel prepared with 60% (v/v) of ethanol. There was a steady effect on the flux of nimodipine (161.02 +/- 4.14 microg/cm2/hr) with an enhancement ratio of 4.56 when carvone was incorporated at a concentration of 10% (w/w) in HPMC gels prepared with 60% (v/v) ethanol. The Fourier transform infrared data indicated that ethanolic solution of carvone increased the transdermal permeability of nimodipine across the rat abdominal skin by partial extraction of lipids in the stratum corneum. The results suggest that 10% (w/w) of carvone in 60% (v/v) ethanol-water, along with HPMC as antinucleating agent may be useful for enhancing the skin permeability of nimodipine from the membrane-moderated transdermal therapeutic system.

  3. Use of a molecular form technique for the penetration of supersaturated solutions of salicylic acid across silicone membranes and human skin in vitro.

    Science.gov (United States)

    Leveque, N; Raghavan, S L; Lane, M E; Hadgraft, J

    2006-08-01

    Permeation enhancement of salicylic acid (SA) from supersaturated solutions formed using a 'molecular form' technique was investigated. In a conventional cosolvent technique, two solvents are used, one in which the drug is considerably more soluble than the other. Propylene glycol and water have been predominantly used as cosolvents to create supersaturation in skin permeation enhancement. In this paper, we report the use of buffer solutions with different pHs as media for producing different molecular forms. Supersaturated solutions were prepared using pH 8:pH 2 (80:20 v/v), which gave a nominal pH when mixed of around 5. Model silicone membranes and human skin were used. Hydroxypropyl methyl cellulose (HPMC) was employed to stabilise the supersaturated states. Stability data showed that while the SA supersaturated solutions without HPMC crystallised between 15 min and 46 h depending on the degree of supersaturation, the solutions with HPMC were stable for more than 2 months. The flux of SA increased with the degree of saturation for solutions prepared in a 80:20 buffer pH 8/buffer pH 2 mixture. Although the fluxes of SA with and without HPMC were similar both through silicone membrane and human skin, HPMC was found to be effective in increasing the stability of supersaturated solutions of SA.

  4. 戊二醛向破坏氢键后绵羊皮胶原中的渗透过程研究%The Penetration of Glutaraldehyde into Sheep Skin Collagen with Broken Hydrogen Bond

    Institute of Scientific and Technical Information of China (English)

    洪婉晨; 陈丽; 褚舒骅; 王亚娟; 蒋岚

    2014-01-01

    The influence of urea solution, which employed as a hydrogen bond breaking agent, on the mi-crostructure and thermal stability of sheep skin collagen was investigated. Skin collagen with broken hy-drogen bond was tanned with glutaraldehyde, and then the concentration of tanning agent and shrinkage temperature of collagen at different stage was measured. By doing this, the penetration of glutaraldehyde into the sheep skin collagen can be explored. The results showed that both thermal stability of collagen and the penetration rate of glutaraldehyde decreased with the increase in urea concentration. The collagen sample treated with 6 mol/L urea solutions possessed the worst thermal stability in this experiment. All these results suggested hydrogen bond played an important but not primary role in stabilizing the confor-mation of collagen fiber.%以尿素为氢键破坏剂,研究了不同浓度尿素对浸酸绵羊皮胶原纤维的形貌及热稳定性的影响,之后以打破氢键后的胶原为原料,通过检测不同鞣制阶段残留在鞣液中的鞣剂浓度及相应皮胶原的收缩温度,探索了戊二醛向其内部的渗透情况。结果发现:尿素浓度越高,对胶原的形貌及收缩温度影响越大;鞣前胶原的氢键被破坏越严重,戊二醛向其内部渗透越慢、越少,最终鞣制后样品的热稳定性也越差;在戊二醛与胶原的结合力中,氢键发挥着一定的积极作用,但不是主要作用。

  5. Ultrastructure and penetration of cell co-culture model of human skin equivalent%细胞共培养人体皮肤类似物超微结构观察及其渗透性测试

    Institute of Scientific and Technical Information of China (English)

    李辉; 王景雁; 林红梅; 于竞新; 章烨雯; 毛颖秋; 吴清

    2016-01-01

    目的:观察人体皮肤类似物模型形态结构,对其屏障功能进行初步评价。方法通过胶原蛋白包被成纤维细胞,制备真皮层,真皮层表面接种角质细胞,浸没培养1周后,气-液界面培养以促进角质细胞的分化形成角质层,3周后收获皮肤模型;通过肉眼观察、电镜观察皮肤类似物的宏观结构和超微结构;以吲哚美辛作为模型药物,进行体外透皮实验考察细胞共培养皮肤类似物模型的屏障功能。结果皮肤类似物形成与人类皮肤相似的真皮层和表皮层,表皮层表面形成完整的角质层,具有与人类皮肤类似的超微结构;24 h 内渗透性实验结果显示皮肤类似物屏障功能略低于大鼠腹部皮肤,但22~24 h,皮肤类似物对模型药的透过速率远小于大鼠腹部皮肤(约为其28%),且2种皮肤模型对吲哚美辛经皮渗透的稳态流速没有显著性差异(P >0.05)。结论皮肤类似物有与人体皮肤相类似的形态结构特征,与大鼠腹部皮肤相比对吲哚美辛有相似的屏障作用,有望替代动物皮肤成为经皮给药系统评价的新型皮肤模型。%Abatract:Objective To observe the structure of human skin equivalent (HSE)model in vitro,and to preliminarily assess the barrier function of HSE.Methods The HSE model was established by two steps:preparation of dermal layer and preparation of full-thickness skin.Keratinocytes were inoculated on the surface of dermal layer prepared by type 1 collagen coating fibroblasts.After submerged cultured for one week,air-liquid interface cultured for three weeks to enhance the proliferation of keratinocytes,the HSE model was obtained.Then the macroscopical structure and electon microscopical structure of HSE were studied.To investigate the barrier function of HSE model,indometacin was selected as the model drug for the penetration testing in vitro.Results The structures similar to dermal layer and

  6. Case Report: Penetrating Cardiac Injury

    Directory of Open Access Journals (Sweden)

    Adem Grbolar

    2013-10-01

    Full Text Available Summary: Penetrating cardiac injurys caused by gunshots and penetrating tools have high mortality rates. The way of injury, how the cardiac area is effected and the presence of cardiac tamponadecauses mortality in different rates. However the better treatment quality of hospitals, increasingoperative techniques, and internel care unit quality has not been change during the years. Searching the literature, we want to present a 42 years old male patient whowas injured by knife and had a 1 cm skin wound on chest with cardiac tamponade. After sternotomy a 7 cm laseration was observed in heart. Cardioraphy was performed.

  7. Rho kinase inhibitor y-27632 prolongs the life span of adult human keratinocytes, enhances skin equivalent development, and facilitates lentiviral transduction.

    NARCIS (Netherlands)

    Bogaard, E.H.J. van den; Rodijk-Olthuis, D.; Jansen, P.A.M.; Vlijmen-Willems, I.M.J.J. van; Erp, P.E.J. van; Joosten, I.; Zeeuwen, P.L.J.M.; Schalkwijk, J.

    2012-01-01

    The use of tissue-engineered human skin equivalents (HSE) for fundamental research and industrial application requires the expansion of keratinocytes from a limited number of skin biopsies donated by adult healthy volunteers or patients. A pharmacological inhibitor of Rho-associated protein kinases,

  8. Proniosomes for Penetration Enhancement in Transdermal System

    Directory of Open Access Journals (Sweden)

    Samita Singla

    2012-06-01

    Full Text Available Over the last few years an inclusive research has been done over provesicular approach for transdermal drug delivery. Skin has a very tough diffusion barrier inhibiting penetration of drug moiety which is rate limiting barrier for penetration of drugs. There are several approaches that deal with penetration enhancement across the skin. Vesicular and provesicular systems are promising amongst them. Vesicular systems including (niosomes, ethosomes, transfersomes and liposomes are promising systems to cross this permeation barrier. But their major drawback is their unstability, which can be overcome by using provesicular approaches like proniosomes, protransfersomes and proliposomes. Provesicular approaches have been proposed to enhance the stability of vesicles. These approaches may overcome skin barrier properties and enhance percutaneous absorption. In these systems both type of drugs, hydrophilic and lipophillic drugs can be incorporated. The focus of this review is to bring together different aspects related to mechanism of skin permeation of provesicular system, proniosomes preparation and its applications as a carrier system

  9. Natural Terpenes as Penetration Enhancers for Transdermal Drug Delivery

    OpenAIRE

    Jun Chen; Qiu-Dong Jiang; Ya-Ping Chai; Hui Zhang; Pei Peng; Xi-Xiong Yang

    2016-01-01

    The greatest hindrance for transdermal drug delivery (TDD) is the barrier property of skin, especially the stratum corneum (SC). Various methodologies have been investigated and developed to enhance the penetration of drugs through the skin. Among them, the most popular approach is the application of penetration enhancers (PEs), including natural terpenes, a very safe and effective class of PEs. In the present paper, we focused on terpenes as skin PEs for TDD. The mechanism of their action, t...

  10. 雷公藤红素醇质体的制备及体外透皮性能研究%Study on Preparation of Celastrol Ethosome and Its Skin Penetration Properties in Vitro

    Institute of Scientific and Technical Information of China (English)

    吴军; 吴明; 刘荻; 马卓

    2015-01-01

    Objective To prepare celastrol ethosomes and to observe the permeability characteristics of the ethosomes which act as the transdermal delivery carriers of celastrol in vitro. Methods Celastrol ethosomes were prepared by ethanol injection method, and then the encapsulation efficiency, particle size, polydispersity index ( PDI) and zeta potential of the ethosomes were analyzed. TP2A intelligent percutaneous penetration instrument was used to compare the skin penetration properties of celastrol ethosomes, celastrol solution and the mixture of blank ethosomes with celastrol solution. Results The prepared celastrol ethosomes were spherical, and the average particle size was (401.3 ± 5.5) nm, PDI was 0.21± 0.02, steady zeta potential was (-2.75 ± 0.1) mV, and average encapsulation efficiency was ( 80.6 ± 0.7) %. The amount of accumulative penetration of celastrol ethosomes at 48 h was 76.86 μg·cm -2 and the permeation rate was 1.640 9 μg·cm -2·h -1, which were significantly higher than the celastrol solution and the mixture of blank ethosomes with celastrol solution. Conclusion The prepared ethosomes have high encapsulation efficiency, uniform particle size and stable quality, and are beneficial to the transdermal absorption of celastrol.%【目的】制备雷公藤红素(Cel)醇质体,并考察醇质体作为雷公藤红素经皮给药载体的渗透特性。【方法】采用乙醇注入法制备雷公藤红素醇质体,并对其包封率、粒径、多分散指数(PDI)及Zeta电位进行分析;采用TP2A型智能透皮试验仪进行体外透皮试验,比较雷公藤红素醇质体、空白醇质体/Cel溶液和Cel溶液的透皮行为。【结果】此方法制备的雷公藤红素醇质体为类球形结构,平均粒径为(401.3±5.5) nm, PDI为(0.21±0.02), Zeta电位为(-2.75±0.1) mV,平均包封率为(80.6±0.7)%;醇质体48 h的累积透过量76.86μg·cm-2,渗透速率为1.6409μg·cm-2·h-1,与空白

  11. Sagging Skin

    Science.gov (United States)

    ... Skin Scars Skin Growths Skin Lesions Spider Veins Stretch Marks Sun-damaged Skin Unwanted Hair Unwanted Tattoos Varicose ... Skin Scars Skin Growths Skin Lesions Spider Veins Stretch Marks Sun-damaged Skin Unwanted Hair Unwanted Tattoos Varicose ...

  12. Skin absorption through atopic dermatitis skin

    DEFF Research Database (Denmark)

    Halling-Overgaard, A-S; Kezic, S; Jakasa, I

    2017-01-01

    Patients with atopic dermatitis have skin barrier impairment in both lesional and non-lesional skin. They are typically exposed to emollients daily and topical anti-inflammatory medicaments intermittently, hereby increasing the risk of developing contact allergy and systemic exposed to chemicals...... ingredients found in these topical preparations. We systematically searched for studies that investigated skin absorption of various penetrants, including medicaments, in atopic dermatitis patients, but also animals with experimentally induced dermatitis. We identified 40 articles, i.e. 11 human studies...... examining model penetrants, 26 human studies examining atopic dermatitis drugs and 3 animal studies. We conclude that atopic dermatitis patients have nearly two-fold increased skin absorption when compared to healthy controls. There is a need for well-designed epidemiological and dermato...

  13. 乙肝疫苗体外经大鼠皮肤渗透与离子导入给药特性研究%In vitro study of transdermal penetration and iontophoresis of hepatitis B vaccines through rat skin

    Institute of Scientific and Technical Information of China (English)

    徐婷; 徐月红; 韦敏燕; 邓礼荷; 吴传斌

    2011-01-01

    对乙肝疫苗进行体外经皮实验以评价疫苗在被动扩散和离子导入情况下的经皮渗透特性.体外透皮研究采用Franz扩散池,以SD大鼠的腹部皮肤为渗透屏障,以酶联免疫法测定药物累积渗透量和在皮肤中的滞留量.乙肝疫苗(质量浓度为23μg·mL-1与46μg·mL-1)经完整皮肤被动扩散的经皮渗透量与皮肤滞留量均极少,24h累积渗透量仅(2.1 ±0.1)ng·cm-2和(2.3±0.1)ng·cm-2.去除角质层后,经皮渗透量与皮肤滞留量分别提高至(383.7±86.2)ng·cm-2和(16.8±4.6)ng·cm-2,是完整皮肤的171.6倍与2.1倍(46μg·mL-1).离子导入对于乙肝疫苗具有明显的经皮渗透促进作用:完整皮肤经皮离子导入6h,乙肝疫苗的累积渗透量是被动扩散6 h的2.7倍(23 μg·mL-1)和6.6倍(46 μg·mL-1);去角质层皮肤离子导入,乙肝疫苗的累积渗透量是被动扩散6 h的1.6倍(23 μg·mL-1)和1.8倍(46 μg·mL-1).离子导入也能显著增加疫苗在皮肤中的滞留量.离子导入6 h疫苗在完整皮肤中的滞留量和去角质层皮肤中的滞留量均与被动扩散24 h的皮肤滞留量接近[完整皮肤:(16.8±4.6)ng·cm2 vs (13.3±5.4)ng·cm-2;去角质层皮肤:(36.7±14.1)ng·cm-2 vs (26.8±11.2)ng·cm-2](P>0.05).研究结果表明,离子导入是促进乙肝疫苗等生物活性大分子经皮渗透的有效手段,有希望应用于乙肝疫苗的经皮免疫领域.%In vitro percutaneous delivery of hepatitis B vaccines was investigated in order to assess the penetration of vaccine under passive diffusion and iontophoresis conditions. The study was carried out using Franz vertical diffusion cell through the hairless abdominal skin of Sprague-Dawley (SD) rats. Enzyme-linked immunosorbent assay (ELISA) was used to determine the cumulative amount of permeation and the retention amount of drug in skin. Passive diffusion alone resulted in less skin permeation and retention of hepatitis B vaccines, only (2.1 ±0.1) ng·cm-2 and (2.3±0

  14. METHOD ON ESTIMATION OF DRUG'S PENETRATED PARAMETERS

    Institute of Scientific and Technical Information of China (English)

    刘宇红; 曾衍钧; 许景锋; 张梅

    2004-01-01

    Transdermal drug delivery system (TDDS) is a new method for drug delivery. The analysis of plenty of experiments in vitro can lead to a suitable mathematical model for the description of the process of the drug's penetration through the skin, together with the important parameters that are related to the characters of the drugs.After the research work of the experiments data,a suitable nonlinear regression model was selected. Using this model, the most important parameter-penetrated coefficient of 20 drugs was computed.In the result one can find, this work supports the theory that the skin can be regarded as singular membrane.

  15. Study of surfactant-skin interactions by skin impedance measurements.

    Science.gov (United States)

    Lu, Guojin; Moore, David J

    2012-02-01

    The stratum corneum (SC) plays a very critical physiological role as skin barrier in regulating water loss through the skin and protects the body from a wide range of physical and chemical exogenous insults. Surfactant-containing formulations can induce skin damage and irritation owing to surfactant absorption and penetration. It is generally accepted that reduction in skin barrier properties occurs only after surfactants have penetrated/permeated into the skin barrier. To mitigate the harshness of surfactant-based cleansing products, penetration/permeation of surfactants should be reduced. Skin impedance measurements have been taken in vitro on porcine skin using vertical Franz diffusion cells to investigate the impact of surfactants, temperature and pH on skin barrier integrity. These skin impedance results demonstrate excellent correlation with other published methods for assessing skin damage and irritation from different surfactant chemistry, concentration, pH, time of exposure and temperature. This study demonstrates that skin impedance can be utilized as a routine approach to screen surfactant-containing formulations for their propensity to compromise the skin barrier and hence likely lead to skin irritation.

  16. β-环糊精和促透剂对辣椒碱经皮透过特性的影响%Effect of β-cyclodextrin and penetration enhancers on in vitro permeation of capsaicin through rat skin

    Institute of Scientific and Technical Information of China (English)

    安茜; 李宏树; 张莉; 陈莉; 张梅平

    2013-01-01

    研究不同浓度β-环糊精及促透剂对辣椒碱体外经皮渗透的影响.[方法]采用改良的Franz扩散池法,以离体鼠皮为透皮屏障,用高效液相色谱法测定接受液中辣椒碱的含量,计算药物的累积透过量,采用滞留时间法求算经皮渗透参数,考察不同浓度β-环糊精以及不同浓度十二烷基硫酸钠(sodium dodecyl sulfate,SDS)、尿素与辣椒碱-β-环糊精包合物对辣椒碱的促透作用.[结果]β-环糊精与辣椒碱形成包合物后透皮速率提高;添加SDS或尿素的辣椒碱-β-环糊精包合物透皮速率进一步增高,其中0.1%SDS的促透效果最为明显,而不同浓度的尿素促透效果相近.[结论]β-环糊精包合的辣椒碱经皮透过量增加,选择10 g/L β-环糊精制备辣椒碱β-环糊精包合物较适宜,SDS或尿素可进一步促进包合物中辣椒碱的透皮吸收.%[Objective] To study the in vitro effects of β -cyclodextrin and 2 kinds of penetration enhancers on the percutaneous absorption of capsaicin through isolated rat skin. [Methods] A modified Franz diffusion apparatus was used in this experiment. HPLC method was established to determine the content of capsaicin in receivers at specified time points. All the percutaneous parameters like amount permeated (Q), diffusivity (Dapp), permeability coefficient (Pm), partition coefficient (Kapp) and release rate constant (J) were calculated statistically. [Results] β-cyclodextrin enhanced the percutaneous absorption of capsaicin. Release rate constant increased more when urea or SDS was added into capsaicin- β -cyclodextrin inclusion compound. 0.1% SDS was more effective for transdermal permeability of capsaicin in rats. [Conclusions] β-cyclodextrin can be used as transdermal permeation enhancer in topical preparation of capsaicin. The optimal concentration of β -cyclodextrin is 10 g/L. The coapplication of SDS and urea can enhance absorption more significantly.

  17. Use of a graphics processing unit (GPU) to facilitate real-time 3D graphic presentation of the patient skin-dose distribution during fluoroscopic interventional procedures.

    Science.gov (United States)

    Rana, Vijay; Rudin, Stephen; Bednarek, Daniel R

    2012-02-23

    We have developed a dose-tracking system (DTS) that calculates the radiation dose to the patient's skin in real-time by acquiring exposure parameters and imaging-system-geometry from the digital bus on a Toshiba Infinix C-arm unit. The cumulative dose values are then displayed as a color map on an OpenGL-based 3D graphic of the patient for immediate feedback to the interventionalist. Determination of those elements on the surface of the patient 3D-graphic that intersect the beam and calculation of the dose for these elements in real time demands fast computation. Reducing the size of the elements results in more computation load on the computer processor and therefore a tradeoff occurs between the resolution of the patient graphic and the real-time performance of the DTS. The speed of the DTS for calculating dose to the skin is limited by the central processing unit (CPU) and can be improved by using the parallel processing power of a graphics processing unit (GPU). Here, we compare the performance speed of GPU-based DTS software to that of the current CPU-based software as a function of the resolution of the patient graphics. Results show a tremendous improvement in speed using the GPU. While an increase in the spatial resolution of the patient graphics resulted in slowing down the computational speed of the DTS on the CPU, the speed of the GPU-based DTS was hardly affected. This GPU-based DTS can be a powerful tool for providing accurate, real-time feedback about patient skin-dose to physicians while performing interventional procedures.

  18. Use of a graphics processing unit (GPU) to facilitate real-time 3D graphic presentation of the patient skin-dose distribution during fluoroscopic interventional procedures

    Science.gov (United States)

    Rana, Vijay; Rudin, Stephen; Bednarek, Daniel R.

    2012-03-01

    We have developed a dose-tracking system (DTS) that calculates the radiation dose to the patient's skin in realtime by acquiring exposure parameters and imaging-system-geometry from the digital bus on a Toshiba Infinix C-arm unit. The cumulative dose values are then displayed as a color map on an OpenGL-based 3D graphic of the patient for immediate feedback to the interventionalist. Determination of those elements on the surface of the patient 3D-graphic that intersect the beam and calculation of the dose for these elements in real time demands fast computation. Reducing the size of the elements results in more computation load on the computer processor and therefore a tradeoff occurs between the resolution of the patient graphic and the real-time performance of the DTS. The speed of the DTS for calculating dose to the skin is limited by the central processing unit (CPU) and can be improved by using the parallel processing power of a graphics processing unit (GPU). Here, we compare the performance speed of GPU-based DTS software to that of the current CPU-based software as a function of the resolution of the patient graphics. Results show a tremendous improvement in speed using the GPU. While an increase in the spatial resolution of the patient graphics resulted in slowing down the computational speed of the DTS on the CPU, the speed of the GPU-based DTS was hardly affected. This GPU-based DTS can be a powerful tool for providing accurate, real-time feedback about patient skin-dose to physicians while performing interventional procedures.

  19. The Skin as a Route of Allergen Exposure: Part II. Allergens and Role of the Microbiome and Environmental Exposures.

    Science.gov (United States)

    Knaysi, George; Smith, Anna R; Wilson, Jeffrey M; Wisniewski, Julia A

    2017-01-01

    This second part of the article aims to highlight recent contributions in the literature that enhance our understanding of the cutaneous immune response to allergen. Several properties of allergens facilitate barrier disruption and cutaneous sensitization. There is a strong epidemiologic relationship between the microbiome, both the gut and skin, and atopic dermatitis (AD). The mechanisms connecting these two entities remain enigmatic; however, recent murine models show that commensal skin bacteria play an active role in supporting skin barrier homeostasis and defense against microbial penetration. Likewise, the association between the lack of colonization with Staph species and AD development suggests a potentially functional role for these organisms in regulating the skin barrier and response to environmental allergens. In undisrupted skin, evidence suggests that the cutaneous route may promote allergen tolerance. Properties of environmental allergens and commensal bacteria add to the complex landscape of skin immunity. Further investigation is needed to elucidate how these properties regulate the cutaneous immune response to allergen.

  20. Rho Kinase Inhibitor Y-27632 Prolongs the Life Span of Adult Human Keratinocytes, Enhances Skin Equivalent Development, and Facilitates Lentiviral Transduction

    Science.gov (United States)

    Rodijk-Olthuis, Diana; Jansen, Patrick A.M.; van Vlijmen-Willems, Ivonne M.J.J.; van Erp, Piet E.; Joosten, Irma; Zeeuwen, Patrick L.J.M.

    2012-01-01

    The use of tissue-engineered human skin equivalents (HSE) for fundamental research and industrial application requires the expansion of keratinocytes from a limited number of skin biopsies donated by adult healthy volunteers or patients. A pharmacological inhibitor of Rho-associated protein kinases, Y-27632, was recently reported to immortalize neonatal human foreskin keratinocytes. Here, we investigated the potential use of Y-27632 to expand human adult keratinocytes and evaluated its effects on HSE development and in vitro gene delivery assays. Y-27632 was found to significantly increase the life span of human adult keratinocytes (up to five to eight passages). The epidermal morphology of HSEs generated from high-passage, Y-27632-treated keratinocytes resembled the native epidermis and was improved by supplementing Y-27632 during the submerged phase of HSE development. In addition, Y-27632-treated keratinocytes responded normally to inflammatory stimuli, and could be used to generate HSEs with a psoriatic phenotype, upon stimulation with relevant cytokines. Furthermore, Y-27632 significantly enhanced both lentiviral transduction efficiency of primary adult keratinocytes and epidermal morphology of HSEs generated thereof. Our study indicates that Y-27632 is a potentially powerful tool that is used for a variety of applications of adult human keratinocytes. PMID:22519508

  1. Impact of adult atopic dermatitis on topical drug penetration

    DEFF Research Database (Denmark)

    Garcia Ortiz, Patricia; Hansen, Steen H; Shah, Vinod P

    2009-01-01

    Appropriate methodologies for the determination of drug penetration in diseased skin have not yet been established. The aim of this study was to determine the cutaneous penetration of a metronidazole cream formulation in atopic dermatitis, employing dermal microdialysis and tape strip sampling...

  2. Glycosphingolipid-facilitated membrane insertion and internalization of cobra cardiotoxin. The sulfatide.cardiotoxin complex structure in a membrane-like environment suggests a lipid-dependent cell-penetrating mechanism for membrane binding polypeptides.

    Science.gov (United States)

    Wang, Chia-Hui; Liu, Jyung-Hurng; Lee, Shao-Chen; Hsiao, Chwan-Deng; Wu, Wen-Guey

    2006-01-06

    Cobra cardiotoxins, a family of basic polypeptides having lipid- and heparin-binding capacities similar to the cell-penetrating peptides, induce severe tissue necrosis and systolic heart arrest in snakebite victims. Whereas cardiotoxins are specifically retained on the cell surface via heparan sulfate-mediated processes, their lipid binding ability appears to be responsible, at least in part, for cardiotoxin-induced membrane leakage and cell death. Although the exact role of lipids involved in toxin-mediated cytotoxicity remains largely unknown, monoclonal anti-sulfatide antibody O4 has recently been shown to inhibit the action of CTX A3, the major cardiotoxin from Taiwan cobra venom, on cardiomyocytes by preventing cardiotoxin-induced membrane leakage and CTX A3 internalization into mitochondria. Here, we show that anti-sulfatide acts by blocking the binding of CTX A3 to the sulfatides in the plasma membrane to prevent sulfatide-dependent CTX A3 membrane pore formation and internalization. We also describe the crystal structure of a CTX A3-sulfatide complex in a membrane-like environment at 2.3 angstroms resolution. The unexpected orientation of the sulfatide fatty chains in the structure allows prediction of the mode of toxin insertion into the plasma membrane. CTX A3 recognizes both the headgroup and the ceramide interfacial region of sulfatide to induce a lipid conformational change that may play a key role in CTX A3 oligomerization and cellular internalization. This proposed lipid-mediated toxin translocation mechanism may also shed light on the cellular uptake mechanism of the amphiphilic cell-penetrating peptides known to involve multiple internalization pathways.

  3. Skin barrier function

    DEFF Research Database (Denmark)

    2016-01-01

    Renowned experts present the latest knowledge Although a very fragile structure, the skin barrier is probably one of the most important organs of the body. Inward/out it is responsible for body integrity and outward/in for keeping microbes, chemicals, and allergens from penetrating the skin. Since...... the role of barrier integrity in atopic dermatitis and the relationship to filaggrin mutations was discovered a decade ago, research focus has been on the skin barrier, and numerous new publications have become available. This book is an interdisciplinary update offering a wide range of information...... on the subject. It covers new basic research on skin markers, including results on filaggrin and on methods for the assessment of the barrier function. Biological variation and aspects of skin barrier function restoration are discussed as well. Further sections are dedicated to clinical implications of skin...

  4. Skin absorption of inorganic lead (PbO) and the effect of skin cleansers.

    Science.gov (United States)

    Filon, Francesca Larese; Boeniger, Mark; Maina, Giovanni; Adami, Gianpiero; Spinelli, Paolo; Damian, Adriano

    2006-07-01

    The aim of this study was to investigate the percutaneous penetration of lead oxide (PbO) powder and the effect of rapid skin decontamination with two different detergents. Franz cells were used to study in vitro PbO skin penetration through human skin during a 24-hour period. The tests were performed without or with decontamination using either Ivory Liquid soap or a new experimental cleanser 30 minutes after the start of exposure. We confirm that PbO can pass through the skin with a median penetration of 2.9 ng/cm (25-75th percentiles 0.35-6). The cleaning procedure using Ivory Liquid soap significantly increased skin penetration with a median value of 23.6 ng/cm (25-75th percentiles 12-47.1; Mann-Whitney U test, P = 0.0002), whereas the new experimental cleanser only marginally increased penetration (7.1 ng/cm). Our results indicate that it is necessary to prevent skin contamination from occurring because a short contact can increase skin content and penetration even if quickly followed by washing. This study demonstrated that PbO powder can pass through the skin and that skin decontamination done after 30 minutes of exposure did not decrease skin absorption occurring over 24 hours and stresses the need to prevent skin contamination when using toxic substances.

  5. Skin Diseases: Skin Health and Skin Diseases

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Skin Diseases Skin Health and Skin Diseases Past Issues / Fall 2008 Table of Contents ... acne to wrinkles Did you know that your skin is the largest organ of your body? It ...

  6. PENETRATION ENHANCERS: A NOVEL STRATEGY FOR ENHANCING TRANSDERMAL DRUG DELIVERY

    Directory of Open Access Journals (Sweden)

    Singla Vikas

    2011-12-01

    Full Text Available Skin penetration enhancers have been used to improve bioavailability and increase the range of drugs to be administered by topical and transdermal route. Enhancement in skin penetration via modification of the stratum corneum by hydration, or via use of chemical enhancers acting on the structure of the stratum corneum lipids and keratin, partitioning and solubility effects. The mechanism of action of penetration enhancers are used as an aid in potential clinical applications. Synthetic chemicals generally used for this purposes are rapidly losing their value in transdermal patches due to reports of their absorption into the systemic circulation and subsequent possible toxic effect upon long term application. Terpenes are included in the list of Generally Recognized as Safe (GRAS substances and have low irritancy potential. In this review, we have discussed the chemical penetration as well as natural penetration enhancement technology for transdermal drug delivery as well as the probable mechanisms of action.

  7. Investigating the potential of essential oils as penetration enhancer for transdermal losartan delivery: Effectiveness and mechanism of action

    Directory of Open Access Journals (Sweden)

    Indu Vashisth

    2014-10-01

    Full Text Available The effect of tea tree oil (TTO, cumin oil (CO, rose oil (RO and aloe vera oil (AVO on the skin permeation of losartan potassium (LP was investigated. In vitro skin permeation studies were carried out using rat skin. The mechanism of skin permeation enhancement of LP by essential oils treatment was evaluated by FTIR, DSC, activation energy measurement and histopathological examination. Both concurrent ethanol/enhancer treatment and neat enhancer pretreatment of rat SC with all the oils produced significance increase in the LP flux over the control. The effectiveness of the oils as the penetration enhancers was found to be in the following descending order: AVO > RO > CO > TTO. However, only AVO was the only enhancer to provide target flux required to deliver the therapeutic transdermal dose of LP. FTIR and DSC spectra of the enhancer treated SC indicated that TTO, CO, RO and AVO increased the LP permeation by extraction of SC lipids. The results of thermodynamic studies and histopathological examination of AVO treated SC suggested additional mechanisms for AVO facilitated permeation i.e. transient reduction in barrier resistance of SC and intracellular transport by dekeratinization of corneocytes which may be attributed to the presence of triglycerides as constituents of AVO. It is feasible to deliver therapeutically effective dose of LP via transdermal route using AVO as penetration enhancer.

  8. Penetration Testing of the OPRA Regolith Penetrator

    Science.gov (United States)

    El Shafie, A.; Kegege, O.; Barrows, S.; Roe, L.; Ulrich, R.

    2008-03-01

    Our work focuses on the mechanical design and penetration forces for the Optical Probe for Regolith Analysis. This is a spike-shaped probe delivered to a planet, asteroid, or cometary body by a lander to provide IR spectroscopy of the subsurface.

  9. Tissue Engineered Human Skin Equivalents

    Directory of Open Access Journals (Sweden)

    Zheng Zhang

    2012-01-01

    Full Text Available Human skin not only serves as an important barrier against the penetration of exogenous substances into the body, but also provides a potential avenue for the transport of functional active drugs/reagents/ingredients into the skin (topical delivery and/or the body (transdermal delivery. In the past three decades, research and development in human skin equivalents have advanced in parallel with those in tissue engineering and regenerative medicine. The human skin equivalents are used commercially as clinical skin substitutes and as models for permeation and toxicity screening. Several academic laboratories have developed their own human skin equivalent models and applied these models for studying skin permeation, corrosivity and irritation, compound toxicity, biochemistry, metabolism and cellular pharmacology. Various aspects of the state of the art of human skin equivalents are reviewed and discussed.

  10. Follicular penetration and targeting.

    Science.gov (United States)

    Lademann, Jürgen; Otberg, Nina; Jacobi, Ute; Hoffman, Robert M; Blume-Peytavi, Ulrike

    2005-12-01

    In the past, intercellular penetration was assumed to be the most important penetration pathway of topically applied substances. First hints that follicular penetration needs to be taken into consideration were confirmed by recent investigations, presented during the workshop "Follicular Penetration and Targeting" at the 4th Intercontinental Meeting of Hair Research Societies", in Berlin 2004. Hair follicles represent an efficient reservoir for the penetration of topically applied substances with subsequent targeting of distinct cell populations, e.g., nestin-expressing follicular bulge cells. The volume of this reservoir can be determined by differential stripping technology. The follicular penetration processes are significantly influenced by the state of the follicular infundibulum; recent experimental investigations could demonstrate that it is essential to distinguish between open and closed hair follicles. Topically applied substances can only penetrate into open hair follicle. Knowledge of follicular penetration is of high clinical relevance for functional targeting of distinct follicular regions. Human hair follicles show a hair-cycle-dependent variation of the dense neuronal and vascular network. Moreover, during hair follicle cycling with initiation of anagen, newly formed vessels occur. Thus, the potential of nestin-expressing hair follicle stem cells to form neurons and blood vessels was investigated.

  11. Skin Keratins.

    Science.gov (United States)

    Wang, Fengrong; Zieman, Abigail; Coulombe, Pierre A

    2016-01-01

    Keratins comprise the type I and type II intermediate filament-forming proteins and occur primarily in epithelial cells. They are encoded by 54 evolutionarily conserved genes (28 type I, 26 type II) and regulated in a pairwise and tissue type-, differentiation-, and context-dependent manner. Keratins serve multiple homeostatic and stress-enhanced mechanical and nonmechanical functions in epithelia, including the maintenance of cellular integrity, regulation of cell growth and migration, and protection from apoptosis. These functions are tightly regulated by posttranslational modifications as well as keratin-associated proteins. Genetically determined alterations in keratin-coding sequences underlie highly penetrant and rare disorders whose pathophysiology reflects cell fragility and/or altered tissue homeostasis. Moreover, keratin mutation or misregulation represents risk factors or genetic modifiers for several acute and chronic diseases. This chapter focuses on keratins that are expressed in skin epithelia, and details a number of basic protocols and assays that have proven useful for analyses being carried out in skin.

  12. Metasploit penetration testing cookbook

    CERN Document Server

    Agarwal, Monika

    2013-01-01

    This book follows a Cookbook style with recipes explaining the steps for penetration testing with WLAN, VOIP, and even cloud computing. There is plenty of code and commands used to make your learning curve easy and quick.This book targets both professional penetration testers as well as new users of Metasploit, who wish to gain expertise over the framework and learn an additional skill of penetration testing, not limited to a particular OS. The book requires basic knowledge of scanning, exploitation, and the Ruby language.

  13. In vitro dermal penetration study of carbofuran, carbosulfan, and furathiocarb

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Kwang-Hyeon [Department of Pharmacology, Inje University, College of Medicine, 614-735, Busan (Korea); Kim, Jeong-Han [School of Agricultural Biotechnology, Seoul National University, 441-744, Suwon (Korea)

    2003-05-01

    In this study, the dermal penetration rate of carbofuran, carbosulfan, and furathiocarb has been measured with rat abdominal skin using the static diffusion cell. The technical grades of three compounds were applied at different doses on skin surface mounted in static diffusion cell and incubated at 32 C for 48 h with shaking. The same procedures were carried out with furathiocarb EC (emulsifiable concentrate) and WP (wettable powder). At regular intervals, the receptor fluid in cell was sampled and analyzed by HPLC. Only carbofuran was found in carbosulfan- or furathiocarb-treated samples, suggesting they converted into carbofuran while passing through the skin layer. The quantity of insecticide penetrating skin increased with time and applied dose. The skin penetration rate increased with the water solubility of insecticides. The dermal penetration rates of carbofuran, furathiocarb, and carbosulfan were determined as 1.05 {mu}g/cm{sup 2} per h (r{sup 2}=0.991), 0.46 {mu}g/cm{sup 2} per h (r{sup 2}=0.984) and 0.14 {mu}g/cm{sup 2} per h (r{sup 2}=0.967), respectively. There was no significant difference in rate of skin penetration between furathiocarb EC (1.42 {mu}g/cm{sup 2} per h, r{sup 2}=0.988) and WP (1.35 {mu}g/cm{sup 2} per h, r{sup 2}=0.982), while furathiocarb technical grade showed a lower skin penetration rate. In vitro models may be used to predict percutaneous absorption and are useful in selecting safer formulations for field application of pesticide. (orig.)

  14. Your Skin

    Science.gov (United States)

    ... Room? What Happens in the Operating Room? Your Skin KidsHealth > For Kids > Your Skin Print A A ... are really dead skin cells. continue Bye-Bye Skin Cells These old cells are tough and strong, ...

  15. Biohydrogels for the In Vitro Re-construction and In Situ Regeneration of Human Skin

    Science.gov (United States)

    Korkina, Liudmila; Kostyuk, Vladimir; Guerra, Liliana

    Natural and synthetic biohydrogels are of great interest for the development of innovative medicinal and cosmetic products feasible for the treatment of numerous skin diseases and age-related changes in skin structure and function. Here, the characteristics of bio-resorbable hydrogels as scaffolds for the in vitro re-construction of temporary skin substitutes or full skin equivalents for further transplantation are reviewed. Another fast developing area of regenerative medicine is the in situ regeneration of human skin. The approach is mainly applicable to activate and facilitate the skin regeneration process and angiogenesis in chronic wounds with impaired healing. In this case, extracellular matrix resembling polymers are used to stimulate cell growth, adhesion, and movement. Better results could be achieved by activation of biocompatible hydrogels either with proteins (growth factors, adhesion molecules or/and cytokines) or with allogenic skin cells producing and releasing these molecules. Hydrogels are widely applied as carriers of low molecular weight substances with antioxidant, anti-inflammatory, anti-ageing, and wound healing action. Incorporation of these substances into hydrogels enhances their penetration through the skin barrier and prevents their destruction by oxidation. Potential roles of hydrogel-based products for modern dermatology and cosmetology are also discussed.

  16. Penetration testing with Perl

    CERN Document Server

    Berdeaux, Douglas

    2014-01-01

    If you are an expert Perl programmer interested in penetration testing or information security, this guide is designed for you. However, it will also be helpful for you even if you have little or no Linux shell experience.

  17. Ultrasound-mediated transdermal drug delivery of fluorescent nanoparticles and hyaluronic acid into porcine skin in vitro

    Science.gov (United States)

    Wang, Huan-Lei; Fan, Peng-Fei; Guo, Xia-Sheng; Tu, Juan; Ma, Yong; Zhang, Dong

    2016-12-01

    Transdermal drug delivery (TDD) can effectively bypass the first-pass effect. In this paper, ultrasound-facilitated TDD on fresh porcine skin was studied under various acoustic parameters, including frequency, amplitude, and exposure time. The delivery of yellow-green fluorescent nanoparticles and high molecular weight hyaluronic acid (HA) in the skin samples was observed by laser confocal microscopy and ultraviolet spectrometry, respectively. The results showed that, with the application of ultrasound exposures, the permeability of the skin to these markers (e.g., their penetration depth and concentration) could be raised above its passive diffusion permeability. Moreover, ultrasound-facilitated TDD was also tested with/without the presence of ultrasound contrast agents (UCAs). When the ultrasound was applied without UCAs, low ultrasound frequency will give a better drug delivery effect than high frequency, but the penetration depth was less likely to exceed 200 μm. However, with the help of the ultrasound-induced microbubble cavitation effect, both the penetration depth and concentration in the skin were significantly enhanced even more. The best ultrasound-facilitated TDD could be achieved with a drug penetration depth of over 600 μm, and the penetration concentrations of fluorescent nanoparticles and HA increased up to about 4-5 folds. In order to get better understanding of ultrasound-facilitated TDD, scanning electron microscopy was used to examine the surface morphology of skin samples, which showed that the skin structure changed greatly under the treatment of ultrasound and UCA. The present work suggests that, for TDD applications (e.g., nanoparticle drug carriers, transdermal patches and cosmetics), protocols and methods presented in this paper are potentially useful. Project partially supported by the National Natural Science Foundation of China (Grant Nos. 81127901, 81227004, 81473692, 81673995, 11374155, 11574156, 11274170, 11274176, 11474001

  18. The 2008 ICOH Workshop on Skin Notation

    DEFF Research Database (Denmark)

    Sartorelli, P; Ahlers, H W; Cherrie, J W

    2010-01-01

    BACKGROUND: On 29 March 2008 the International Commission on Occupational Health (ICOH) Scientific Committee on Occupational and Environmental Dermatoses organized a Skin Notation Workshop hosted by the 11th International Percutaneous Penetration Perspectives Conference (La Grande Motte, France)....

  19. Chemical engineering of cell penetrating antibodies.

    Science.gov (United States)

    Zhao, Y; Lou, D; Burkett, J; Kohler, H

    2001-08-01

    Antibodies, being exquisitely specific tools in biology, are routinely used to detect and identify intra-cellular structures. However, current intra-cellular application of antibodies requires that the membrane be rendered leaky, resulting in the death of cells. Here, we present a novel method to allow antibodies to penetrate the cellular membrane of living cells without affecting cell viability. A peptide (MTS, membrane transport sequence) that facilitates transport across membranes has been site-specifically attached to antibodies. MTS-antibodies enter the living cells in culture and can be detected by immunofluorescence and ELISA after extraction. Cellular structures are visualized in living cells using a specific MTS-antibody. Antibodies with membrane penetrating properties can become an important tool for the study of intra-cellular processes in living cells. Furthermore, such membrane penetrating antibodies can be used to selectively stimulate or suppress functions of the cellular machinery.

  20. Physics of Armour penetration

    Directory of Open Access Journals (Sweden)

    Sampooran Singh

    1953-01-01

    Full Text Available When a “Shaped-Charge” projectile is spin-stabilized during its flight, its penetration is greatly reduced, hence such a projectile is fin-stabilized and consequently the range is less and accuracy is poor. Attempts are being made to combine the penetrating power of a bazooka, and range and accuracy of rifled weapon. Just as the introduction of fire-arms brought about the extinction of the armour knights because a bullet could easily penetrate the kind of armour that the knights could put on; similarly “Shaped-Charge” projectiles having the range and accuracy of a rifled weapon will seriously affect the tactical use of amour in the battle-field.

  1. Session: Hard Rock Penetration

    Energy Technology Data Exchange (ETDEWEB)

    Tennyson, George P. Jr.; Dunn, James C.; Drumheller, Douglas S.; Glowka, David A.; Lysne, Peter

    1992-01-01

    This session at the Geothermal Energy Program Review X: Geothermal Energy and the Utility Market consisted of five presentations: ''Hard Rock Penetration - Summary'' by George P. Tennyson, Jr.; ''Overview - Hard Rock Penetration'' by James C. Dunn; ''An Overview of Acoustic Telemetry'' by Douglas S. Drumheller; ''Lost Circulation Technology Development Status'' by David A. Glowka; ''Downhole Memory-Logging Tools'' by Peter Lysne.

  2. Ground penetrating radar

    CERN Document Server

    Daniels, David J

    2004-01-01

    Ground-penetrating radar has come to public attention in recent criminal investigations, but has actually been a developing and maturing remote sensing field for some time. In the light of recent expansion of the technique to a wide range of applications, the need for an up-to-date reference has become pressing. This fully revised and expanded edition of the best-selling Surface-Penetrating Radar (IEE, 1996) presents, for the non-specialist user or engineer, all the key elements of this technique, which span several disciplines including electromagnetics, geophysics and signal processing. The

  3. Skin Biopsy

    Science.gov (United States)

    ... I Help Someone Who's Being Bullied? Volunteering Skin Biopsy KidsHealth > For Teens > Skin Biopsy Print A A ... español Biopsia de piel What Is a Skin Biopsy and Who Would Need One? In a biopsy, ...

  4. Skin Conditions

    Science.gov (United States)

    Your skin is your body's largest organ. It covers and protects your body. Your skin Holds body fluids in, preventing dehydration Keeps harmful ... it Anything that irritates, clogs, or inflames your skin can cause symptoms such as redness, swelling, burning, ...

  5. Compound antimalarial ethosomal cataplasm: preparation, evaluation, and mechanism of penetration enhancement.

    Science.gov (United States)

    Shen, Shuo; Liu, Shu-Zhi; Zhang, Yu-Shi; Du, Mao-Bo; Liang, Ai-Hua; Song, Li-Hua; Ye, Zu-Guang

    2015-01-01

    Malaria is still a serious public health problem in some parts of the world. The problems of recurrence and drug resistance are increasingly more serious. Thus, it is necessary to develop a novel antimalarial agent. The objectives of this study were to construct a novel compound antimalarial transdermal nanosystem-ethosomal cataplasm, to investigate its characteristics and efficiency, and to systematically explore the penetration-enhancing mechanisms of ethosomal cataplasm. Artesunate-loaded ethosomes and febrifugine-loaded ethosomes were prepared, and their characteristics were evaluated. Drug-loaded ethosomes were incorporated in the matrix of cataplasm to form the compound antimalarial ethosomal cataplasm. With the help of ethosomal technology, the accumulated permeation quantity of artesunate significantly increased at 8 hours after administration, which was 1.57 times as much as that of conventional cataplasm. Soon after administration, the ethosomal cataplasm could make a large quantity of antimalarial drug quickly penetrate through skin, then the remaining drug in the ethosomal cataplasm could be steadily released. These characteristics of ethosomal cataplasm are favorable for antimalarial drugs to kill Plasmodium spp. quickly and prevent the resurgence of Plasmodium spp. As expected, the ethosomal cataplasm showed good antimalarial efficiency in this experiment. The negative conversion rates were 100% and the recurrence rates were 0% at all dosages. The mechanism of penetration enhancement of the ethosomal cataplasm was systematically explored using an optics microscope, polarization microscope, and transmission electron microscopy. The microstructure, ultrastructure, and birefringent structure in skin were observed. Data obtained in this study showed that the application of ethosomal technology to antimalarial cataplasm could improve the transdermal delivery of drug, enhance the efficacy, and facilitate practical application in clinic.

  6. Tumor penetrating peptides

    Directory of Open Access Journals (Sweden)

    Tambet eTeesalu

    2013-08-01

    Full Text Available Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC, contains the integrin-binding RGD motif. RGD mediates tumor homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular zip code of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is

  7. Skin abscess

    Science.gov (United States)

    Abscess - skin; Cutaneous abscess; Subcutaneous abscess; MRSA - abscess; Staph infection - abscess ... Skin abscesses are common and affect people of all ages. They occur when an infection causes pus ...

  8. [Skin to skin contact and breast-feeding after birth: not always without risk!

    NARCIS (Netherlands)

    Matthijsse, P.R.; Semmekrot, B.A.; Liem, K.D.

    2016-01-01

    Skin-to-skin contact after birth is propagated to facilitate breast-feeding and mother-child bonding. We describe two term infants with sudden unexpected postnatal collapse (SUPC) during skin-to-skin contact. The infants were found with abnormal colour, hypotonia and apnoea, in a prone position on t

  9. [Skin to skin contact and breast-feeding after birth: not always without risk!

    NARCIS (Netherlands)

    Matthijsse, P.R.; Semmekrot, B.A.; Liem, K.D.

    2016-01-01

    Skin-to-skin contact after birth is propagated to facilitate breast-feeding and mother-child bonding. We describe two term infants with sudden unexpected postnatal collapse (SUPC) during skin-to-skin contact. The infants were found with abnormal colour, hypotonia and apnoea, in a prone position on

  10. Influence of metabolism in skin on dosimetry after topical exposure.

    OpenAIRE

    1994-01-01

    Metabolism of chemicals occurs in skin and therefore should be taken into account when one determines topical exposure dose. Skin metabolism is difficult to measure in vivo because biological specimens may also contain metabolites from other tissues. Metabolism in skin during percutaneous absorption can be studied with viable skin in flow-through diffusion cells. Several compounds metabolized by microsomal enzymes in skin (benzo[a]pyrene and 7-ethoxycoumarin) penetrated human and hairless gui...

  11. Effects of soap-water wash on human epidermal penetration.

    Science.gov (United States)

    Zhu, Hanjiang; Jung, Eui-Chang; Phuong, Christina; Hui, Xiaoying; Maibach, Howard

    2016-08-01

    Skin decontamination is a primary interventional method used to decrease dermal absorption of hazardous contaminants, including chemical warfare agents, pesticides and industrial pollutants. Soap and water wash, the most common and readily available decontamination system, may enhance percutaneous absorption through the "wash-in effect." To understand better the effect of soap-water wash on percutaneous penetration, and provide insight to improving skin decontamination methods, in vitro human epidermal penetration rates of four C(14) -labeled model chemicals (hydroquinone, clonidine, benzoic acid and paraoxon) were assayed using flow-through diffusion cells. Stratum corneum (SC) absorption rates of these chemicals at various hydration levels (0-295% of the dry SC weights) were determined and compared with the results of the epidermal penetration study to clarify the effect of SC hydration on skin permeability. Results showed accelerated penetration curves of benzoic acid and paraoxon after surface wash at 30 min postdosing. Thirty minutes after washing (60 min postdosing), penetration rates of hydroquinone and benzoic acid decreased due to reduced amounts of chemical on the skin surface and in the SC. At the end of the experiment (90 min postdosing), a soap-water wash resulted in lower hydroquinone penetration, greater paraoxon penetration and similar levels of benzoic acid and clonidine penetration compared to penetration levels in the non-wash groups. The observed wash-in effect agrees with the enhancement effect of SC hydration on the SC chemical absorption rate. These results suggest SC hydration derived from surface wash to be one cause of the wash-in effect. Further, the occurrence of a wash-in effect is dependent on chemical identity and elapsed time between exposure and onset of decontamination. By reducing chemical residue quantity on skin surface and in the SC reservoir, the soap-water wash may decrease the total quantity of chemical absorbed in the

  12. Utilization of reconstructed cultured human skin models as an alternative skin for permeation studies of chemical compounds

    OpenAIRE

    Kano, Satoshi; 藤堂, 浩明; 杉江, 謙一; 藤本, 英哲; 中田, 圭一; 徳留, 嘉寛; 橋本, フミ惠; 杉林, 堅次

    2010-01-01

    Two reconstructed human skin models, EpiskinSM and EpiDermTM, have been approved as alternative membranes for skin corrosive/irritation experiments due to their close correlation with animal skin. Such reconstructed human skin models were evaluated as alternative membranes for skin permeation experiments. Seven drugs with different lipophilicities and almost the same molecular weight were used as test penetrants. Relationships were investigated between permeability coefficients (P values) of ...

  13. Skin Infections

    Science.gov (United States)

    ... Old Feeding Your 8- to 12-Month-Old Feeding Your 1- to 2-Year-Old First Aid: Skin ... (bacterial infection of the deeper layers of the skin and tissues beneath) are typical childhood skin infections. The usual bacterial culprits in skin ...

  14. Python penetration testing essentials

    CERN Document Server

    Mohit

    2015-01-01

    If you are a Python programmer or a security researcher who has basic knowledge of Python programming and want to learn about penetration testing with the help of Python, this book is ideal for you. Even if you are new to the field of ethical hacking, this book can help you find the vulnerabilities in your system so that you are ready to tackle any kind of attack or intrusion.

  15. Skin Biomes.

    Science.gov (United States)

    Fyhrquist, N; Salava, A; Auvinen, P; Lauerma, A

    2016-05-01

    The cutaneous microbiome has been investigated broadly in recent years and some traditional perspectives are beginning to change. A diverse microbiome exists on human skin and has a potential to influence pathogenic microbes and modulate the course of skin disorders, e.g. atopic dermatitis. In addition to the known dysfunctions in barrier function of the skin and immunologic disturbances, evidence is rising that frequent skin disorders, e.g. atopic dermatitis, might be connected to a dysbiosis of the microbial community and changes in the skin microbiome. As a future perspective, examining the skin microbiome could be seen as a potential new diagnostic and therapeutic target in inflammatory skin disorders.

  16. Optical coherence tomography for imaging of skin and skin diseases

    DEFF Research Database (Denmark)

    Mogensen, Mette; Thrane, Lars; Jørgensen, Thomas Martini

    2009-01-01

    , as have many diseases. The method can provide accurate measures of epidermal and nail changes in normal tissue. Skin cancer and other tumors, as well as inflammatory diseases, have been studied and good agreement found between OCT images and histopathological architecture. OCT also allows noninvasive......Optical coherence tomography (OCT) is an emerging imaging technology based on light reflection. It provides real-time images with up to 2-mm penetration into the skin and a resolution of approximately 10 μm. It is routinely used in ophthalmology. The normal skin and its appendages have been studied...... monitoring of morphologic changes in skin diseases and may have a particular role in the monitoring of medical treatment of nonmelanoma skin cancer. The technology is however still evolving and continued technological development will necessitate an ongoing evaluation of its diagnostic accuracy. Several...

  17. Market penetration of biodiesel

    Directory of Open Access Journals (Sweden)

    Kenneth R. Szulczyk, Bruce A. McCarl

    2010-01-01

    Full Text Available This research examines in detail the technology and economics of substituting biodiesel for diesel #2. This endeavor examines three areas. First, the benefits of biodiesel are examined, and the technical problems of large-scale implementation. Second, the biodiesel production possibilities are examined for soybean oil, corn oil, tallow, and yellow grease, which are the largest sources of feedstocks for the United States. Examining in detail the production possibilities allows to identity the extent of technological change, production costs, byproducts, and greenhouse gas (GHG emissions. Finally, a U.S. agricultural model, FASOMGHG was used to predict market penetration of biodiesel, given technological progress, variety of technologies and feedstocks, market interactions, energy prices, and carbon dioxide equivalent prices. FASOMGHG has several interesting results. First, diesel fuel prices have an expansionary impact on the biodiesel industry. The higher the diesel fuel prices, the more biodiesel is produced. However, given the most favorable circumstances, the maximum biodiesel market penetration is 9% in 2030 with a wholesale diesel price of $4 per gallon. Second, the two dominant sources of biodiesel are from corn and soybeans. Sources like tallow and yellow grease are more limited, because they are byproducts of other industries. Third, GHG prices have an expansionary impact on the biodiesel prices, because biodiesel is quite GHG efficient. Finally, U.S. government subsidies on biofuels have an expansionary impact on biodiesel production, and increase market penetration at least an additional 3%.

  18. Market penetration of biodiesel

    Energy Technology Data Exchange (ETDEWEB)

    Szulczyk, Kenneth R. [Department of Economics, Orbita 3, Suleyman Demirel University, Almaty, 050043 (Kazakhstan); McCarl, Bruce A. [Department of Agricultural Economics, 2124 TAMU, Texas A& amp; M University, College Station, Texas, 77843 (United States)

    2010-07-01

    This research examines in detail the technology and economics of substituting biodiesel for diesel number 2. This endeavor examines three areas. First, the benefits of biodiesel are examined, and the technical problems of large-scale implementation. Second, the biodiesel production possibilities are examined for soybean oil, corn oil, tallow, and yellow grease, which are the largest sources of feedstocks for the United States. Examining in detail the production possibilities allows to identity the extent of technological change, production costs, byproducts, and greenhouse gas (GHG) emissions. Finally, a U.S. agricultural model, FASOMGHG was used to predict market penetration of biodiesel, given technological progress, variety of technologies and feedstocks, market interactions, energy prices, and carbon dioxide equivalent prices. FASOMGHG has several interesting results. First, diesel fuel prices have an expansionary impact on the biodiesel industry. The higher the diesel fuel prices, the more biodiesel is produced. However, given the most favorable circumstances, the maximum biodiesel market penetration is 9% in 2030 with a wholesale diesel price of $4 per gallon. Second, the two dominant sources of biodiesel are from corn and soybeans. Sources like tallow and yellow grease are more limited, because they are byproducts of other industries. Third, GHG prices have an expansionary impact on the biodiesel prices, because biodiesel is quite GHG efficient. Finally, U.S. government subsidies on biofuels have an expansionary impact on biodiesel production, and increase market penetration at least an additional 3%.

  19. Prediction of alumina penetration

    Energy Technology Data Exchange (ETDEWEB)

    Mandell, D A

    1993-02-01

    The MESA hydrocode was used to predict two-dimensional tests of L/D 10 and L/D 15 tungsten rods impacting AD 90 alumina with a steel backing. The residual penetration into the steel is the measured quantity in these experiments conducted at the Southwest Research Institute (SWR). The interface velocity as a function of time between an alumina target and a lithium fluoride window, impacted by an alumina disk at velocities between 544 m/s and 2329 m/s, was also predicted. These one-dimensional flyer plate experiments were conducted at Sandia National Laboratories using Coors AD 995 alumina. The material strength and fracture models are important in the prediction of ceramic experiments. The models used in these predictions are discussed. The penetrations in the two-dimensional tests were predicted to 11.4 percent or better. In five of the six experiments, the predicted penetration depth was deeper than the measured value. This trend is expected since the calculation is based on ideal conditions. The results show that good agreement between the 1-D flyer plate data and the MESA predictions exists at the lower impact velocities, but the maximum velocity is overpredicted as the flyer plate velocity increases. At a flyer plate velocity of 2329 m/s the code overpredicted the data by 12.3 percent.

  20. Ethnische Unterschiede in der Hautphysiologie, Haarfollikelmorphologie und follikulären Penetration von topisch applizierten Substanzen

    OpenAIRE

    Luther, Natalie

    2012-01-01

    There is increasing evidence that different ethnic groups exhibit varieties in skin physiological parameters and penetration behaviour, although data available are inconsistent. Likewise variations in hair follicle morphology have been described although its influence on the follicular penetration process has not been investigated until now. Therefore, the aim of the present study was to investigate skin physiological parameters, the hair follicle morphology and the follicular and interce...

  1. An Overview of Penetration Testing

    OpenAIRE

    2011-01-01

    Penetration testing is a series of activities undertaken to identify and exploit security vulnerabilities. It helps confirm the effectiveness or ineffectiveness of the security measures that have been implemented. This paper provides an overview of penetration testing. It discusses the benefits, the strategies and the methodology of conducting penetration testing. The methodology of penetration testing includes three phases: test preparation, test and test analysis. The test phase involves ...

  2. A technique for pediatric total skin electron irradiation

    Directory of Open Access Journals (Sweden)

    Bao Qinan

    2012-03-01

    Full Text Available Abstract Background Total skin electron irradiation (TSEI is a special radiotherapy technique which has generally been used for treating adult patients with mycosis fungoides. Recently, two infants presented with leukemia cutis isolated to the skin requiring TSEI. This work discusses the commissioning and quality assurance (QA methods for implementing a modified Stanford technique using a rotating harness system to position sedated pediatric patients treated with electrons to the total skin. Methods and Results Commissioning of pediatric TSEI consisted of absolute calibration, measurement of dosimetric parameters, and subsequent verification in a pediatric patient sized cylindrical phantom using radiographic film and optically stimulated luminance (OSL dosimeters. The depth of dose penetration under TSEI treatment condition was evaluated using radiographic film sandwiched in the phantom and demonstrated a 2 cm penetration depth with the maximum dose located at the phantom surface. Dosimetry measurements on the cylindrical phantom and in-vivo measurements from the patients suggested that, the factor relating the skin and calibration point doses (i.e., the B-factor was larger for the pediatric TSEI treatments as compared to adult TSEI treatments. Custom made equipment, including a rotating plate and harness, was fabricated and added to a standard total body irradiation stand and tested to facilitate patient setup under sedated condition. A pediatric TSEI QA program, consisting of daily output, energy, flatness, and symmetry measurements as well as in-vivo dosimetry verification for the first cycle was developed. With a long interval between pediatric TSEI cases, absolute dosimetry was also repeated as part of the QA program. In-vivo dosimetry for the first two infants showed that a dose of ± 10% of the prescription dose can be achieved over the entire patient body. Conclusion Though pediatric leukemia cutis and the subsequent need for TSEI are

  3. Millimeter wave dosimetry of human skin.

    Science.gov (United States)

    Alekseev, S I; Radzievsky, A A; Logani, M K; Ziskin, M C

    2008-01-01

    To identify the mechanisms of biological effects of mm waves it is important to develop accurate methods for evaluating absorption and penetration depth of mm waves in the epidermis and dermis. The main characteristics of mm wave skin dosimetry were calculated using a homogeneous unilayer model and two multilayer models of skin. These characteristics included reflection, power density (PD), penetration depth (delta), and specific absorption rate (SAR). The parameters of the models were found from fitting the models to the experimental data obtained from measurements of mm wave reflection from human skin. The forearm and palm data were used to model the skin with thin and thick stratum corneum (SC), respectively. The thin SC produced little influence on the interaction of mm waves with skin. On the contrary, the thick SC in the palm played the role of a matching layer and significantly reduced reflection. In addition, the palmar skin manifested a broad peak in reflection within the 83-277 GHz range. The viable epidermis plus dermis, containing a large amount of free water, greatly attenuated mm wave energy. Therefore, the deeper fat layer had little effect on the PD and SAR profiles. We observed the appearance of a moderate SAR peak in the therapeutic frequency range (42-62 GHz) within the skin at a depth of 0.3-0.4 mm. Millimeter waves penetrate into the human skin deep enough (delta = 0.65 mm at 42 GHz) to affect most skin structures located in the epidermis and dermis.

  4. Neuromodulators for Aging Skin

    Science.gov (United States)

    ... Skin Scars Skin Growths Skin Lesions Spider Veins Stretch Marks Sun-damaged Skin Unwanted Hair Unwanted Tattoos Varicose ... Skin Scars Skin Growths Skin Lesions Spider Veins Stretch Marks Sun-damaged Skin Unwanted Hair Unwanted Tattoos Varicose ...

  5. An Overview of Penetration Testing

    Directory of Open Access Journals (Sweden)

    Aileen G. Bacudio

    2011-12-01

    Full Text Available Penetration testing is a series of activities undertaken to identify and exploit security vulnerabilities. It helps confirm the effectiveness or ineffectiveness of the security measures that have been implemented. This paper provides an overview of penetration testing. It discusses the benefits, the strategies and the methodology of conducting penetration testing. The methodology of penetration testing includes three phases: test preparation, test and test analysis. The test phase involves the following steps: information gathering, vulnerability analysis, and vulnerability exploit. This paper further illustrates how to apply this methodology to conduct penetration testing on two example web applications.

  6. Dermal absorption and skin damage following hydrofluoric acid exposure in an ex vivo human skin model.

    Science.gov (United States)

    Dennerlein, Kathrin; Kiesewetter, Franklin; Kilo, Sonja; Jäger, Thomas; Göen, Thomas; Korinth, Gintautas; Drexler, Hans

    2016-04-25

    The wide industrial use of hydrofluoric acid (HF) poses a high risk for accidental dermal exposure. Despite local and systemic hazards associated with HF, information on percutaneous penetration and tissue damage is rare. In the present ex vivo study, the dermal absorption of HF (detected in terms of fluoride ions) was quantified and the skin damaging potential as a function of concentration and exposure duration was assessed. Percutaneous penetration of HF (c=5, 30, and 50%) at 3 exposure durations (3, 5, and 10 min) was investigated in a static diffusion cell model using freshly excised human skin. Alterations of skin were histologically evaluated. HF rapidly penetrated through skin under formation of a considerable intradermal reservoir (∼ 13-67% of total absorbed fluoride). Histologically, epidermal alterations were detected already after exposure to 5% HF for 3 min. The degree of skin damage increased with rising concentration and exposure duration leading to coagulation necrosis. For HF concentrations of ≥ 30%, skin damage progressed into deeper skin layers. Topically applied HF concentration was the principal parameter determining HF induced skin effects. The intradermal HF retention capacity associated with progression and prolongation of HF induced skin effects must be considered in the review of skin decontamination procedures.

  7. Penetration Testing: A Review

    Directory of Open Access Journals (Sweden)

    Kumar Shravan

    2014-04-01

    Full Text Available : Network Security is becoming more and more crucial as the volume of data being exchanged on the Internet increases. When people use Internet, they have certain expectations. They expect confidentiality, data integrity and authentication (CIA Standards. In 1980’s most organizations had only a physical boundary that needed protection of the assets. Today, due to the changes in the way resources are made available Organizations are forced to verify that their assets are protected from both the external and internal threats that our working environment has enabled. Due to the increasing dependency of our society on networked information system the overall security of these systems should be measured and improved. The most accurate method to evaluate organization’s information security stance is to observe how it stands up against an attack. Network administrators have often tried their best by improving their network security, however with rapid surface of new exploits; the best way of ensuring that the system is secure is to attempt penetration testing. This would be the most effective way to find exploits and to proof whether a system is vulnerable. Penetration test ing often allows the security analyst to find new vulnerabilities.

  8. Influence of the Vehicle on the Penetration of Particles into Hair Follicles

    Directory of Open Access Journals (Sweden)

    Ute Wank

    2011-06-01

    Full Text Available Recently, it has been demonstrated that particulate substances penetrate preferentially into the hair follicles and that the penetration depth depends on the particle size. In the present study, the influence of the vehicle of the particulate substances on the penetration depth was investigated. Four different formulations (ethanolic suspension, aqueous suspension, ethanolic gel and aqueous gel containing peptide-loaded particles of 1 µm in diameter were prepared and applied on porcine ear skin. After penetration, punch biopsies were taken and the penetration depths of the particles were investigated by laser scanning microscopy. The deepest penetration was achieved with the gel formulations demonstrating an influence of the vehicle on the penetration depth of particulate substances.

  9. Predicting chemically-induced skin reactions. Part II: QSAR models of skin permeability and the relationships between skin permeability and skin sensitization

    Energy Technology Data Exchange (ETDEWEB)

    Alves, Vinicius M. [Laboratory of Molecular Modeling and Design, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO 74605-220 (Brazil); Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Muratov, Eugene [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Laboratory of Theoretical Chemistry, A.V. Bogatsky Physical–Chemical Institute NAS of Ukraine, Odessa 65080 (Ukraine); Fourches, Denis [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Strickland, Judy; Kleinstreuer, Nicole [ILS/Contractor supporting the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), P.O. Box 13501, Research Triangle Park, NC 27709 (United States); Andrade, Carolina H. [Laboratory of Molecular Modeling and Design, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO 74605-220 (Brazil); Tropsha, Alexander, E-mail: alex_tropsha@unc.edu [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States)

    2015-04-15

    sensitization and skin permeability has been found. • Structural rules for optimizing sensitization and penetration were established.

  10. Skin Cancer

    Science.gov (United States)

    ... are round and lie directly under squamous cells. Melanocytes are specialized skin cells that produce pigment called melanin. The melanin pigment produced by melanocytes gives skin its color. It also protects the ...

  11. Skin turgor

    Science.gov (United States)

    ... arm or abdomen is checked. The skin is held for a few seconds then released. Skin with ... University of Washington, Seattle, WA. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the ...

  12. Skin Cancer

    Science.gov (United States)

    Skin cancer is the most common form of cancer in the United States. The two most common types ... face, neck, hands, and arms. Another type of skin cancer, melanoma, is more dangerous but less common. Anyone ...

  13. Penetration Dynamics of Earth Penetration Warhead into Composite Target Media

    Directory of Open Access Journals (Sweden)

    P. K. Roy

    1987-07-01

    Full Text Available Attempts have been made to develop a suitable computer code that can find solutions to the axi-symmetric penetration of an Earth Penetrating Warhead yielding complete space-time histories of the resistive force offered by the target medium. The consequent warhead deceleration and velocity reduction, the resulting axial compressive stress developed in warhead casing as the penetration process progresses into the composite target media consisting of hard concrete of specified thickness followed by earth soil have been discussed.

  14. Skin Aging

    Science.gov (United States)

    Your skin changes as you age. You might notice wrinkles, age spots and dryness. Your skin also becomes thinner and loses fat, making it ... heal, too. Sunlight is a major cause of skin aging. You can protect yourself by staying out ...

  15. Skin Bioprinting: Impending Reality or Fantasy?

    Science.gov (United States)

    Ng, Wei Long; Wang, Shuai; Yeong, Wai Yee; Naing, May Win

    2016-09-01

    Bioprinting provides a fully automated and advanced platform that facilitates the simultaneous and highly specific deposition of multiple types of skin cells and biomaterials, a process that is lacking in conventional skin tissue-engineering approaches. Here, we provide a realistic, current overview of skin bioprinting, distinguishing facts from myths. We present an in-depth analysis of both current skin bioprinting works and the cellular and matrix components of native human skin. We also highlight current limitations and achievements, followed by design considerations and a future outlook for skin bioprinting. The potential of bioprinting with converging opportunities in biology, material, and computational design will eventually facilitate the fabrication of improved tissue-engineered (TE) skin constructs, making bioprinting skin an impending reality.

  16. Follicular and percutaneous penetration pathways of topically applied minoxidil foam.

    Science.gov (United States)

    Blume-Peytavi, Ulrike; Massoudy, Lida; Patzelt, Alexa; Lademann, Jürgen; Dietz, Ekkehart; Rasulev, Utkur; Garcia Bartels, Natalie

    2010-11-01

    In the past, it was assumed that the intercellular route was the only relevant penetration pathway for topically applied substances. Recent results on follicular penetration emphasize that the hair follicles represent a highly relevant and efficient penetration pathway and reservoir for topically applied substances. This study investigates a selective closure technique of hair follicle orifices in vivo assessing interfollicular and follicular absorption rates of topical minoxidil foam in humans. In delimited skin area, single hair orifices or interfollicular skin were blocked with a microdrop of special varnish-wax-mixture in vivo. Minoxidil foam (5%) was topically applied, and transcutaneous absorption was measured by a new surface ionization mass spectrometry technique in serum. Different settings (open, closed or none of both) enabled to clearly distinguish between interfollicular and follicular penetration of the topically applied minoxidil foam. Five minutes after topical application, minoxidil was detected in blood samples when follicles remained open, whereas with closed follicles 30 min were needed. Highest levels were found first when both pathways were open, followed by open follicles and subsequently by closed follicles. These results demonstrate the high importance of the follicular penetration pathway. Hair follicles are surrounded by a dense network of blood capillaries and dendritic cells and have stem cells in their immediate vicinity, making them ideal targets for drug delivery. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Penetration and lateral diffusion characteristics of polycrystalline graphene barriers

    Science.gov (United States)

    Yoon, Taeshik; Mun, Jeong Hun; Cho, Byung Jin; Kim, Taek-Soo

    2013-12-01

    We report penetration and lateral diffusion behavior of environmental molecules on synthesized polycrystalline graphene. Penetration occurs through graphene grain boundaries resulting in local oxidation. However, when the penetrated molecules diffuse laterally, the oxidation region will expand. Therefore, we measured the lateral diffusion rate along the graphene-copper interface for the first time by the environment-assisted crack growth test. It is clearly shown that the lateral diffusion is suppressed due to the high van der Waals interaction. Finally, we employed bilayer graphene for a perfect diffusion barrier facilitated by decreased defect density and increased lateral diffusion path.We report penetration and lateral diffusion behavior of environmental molecules on synthesized polycrystalline graphene. Penetration occurs through graphene grain boundaries resulting in local oxidation. However, when the penetrated molecules diffuse laterally, the oxidation region will expand. Therefore, we measured the lateral diffusion rate along the graphene-copper interface for the first time by the environment-assisted crack growth test. It is clearly shown that the lateral diffusion is suppressed due to the high van der Waals interaction. Finally, we employed bilayer graphene for a perfect diffusion barrier facilitated by decreased defect density and increased lateral diffusion path. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr03849a

  18. Natural Terpenes as Penetration Enhancers for Transdermal Drug Delivery.

    Science.gov (United States)

    Chen, Jun; Jiang, Qiu-Dong; Chai, Ya-Ping; Zhang, Hui; Peng, Pei; Yang, Xi-Xiong

    2016-12-11

    The greatest hindrance for transdermal drug delivery (TDD) is the barrier property of skin, especially the stratum corneum (SC). Various methodologies have been investigated and developed to enhance the penetration of drugs through the skin. Among them, the most popular approach is the application of penetration enhancers (PEs), including natural terpenes, a very safe and effective class of PEs. In the present paper, we focused on terpenes as skin PEs for TDD. The mechanism of their action, the factors affecting their penetration enhancement effect, as well as their possible skin toxicity were discussed. Terpenes abundant in nature have great potential in the development of PEs. Compared to synthetic PEs, natural terpenes have been proved to possess higher enhancement activity. Interaction with SC intercellular lipids is the main mechanism of action for terpenes. The key factor affecting the enhancement effect is the lipophilicity of both terpenes and drug molecules. In addition, a lot of terpenes have also been proved to be much less toxic compared to azone, the classic synthetic PE. In summary, terpenes may be preferred over the chemically synthesized compounds as safe and effective PEs to promote the percutaneous absorption of drugs.

  19. A Novel Murine Model for the In Vivo Study of Transdermal Drug Penetration

    Directory of Open Access Journals (Sweden)

    Gábor Eros

    2012-01-01

    Full Text Available Enhancement of the transdermal penetration of different active agents is an important research goal. Our aim was to establish a novel in vivo experimental model which provides a possibility for exact measurement of the quantity of penetrated drug. The experiments were performed on SKH-1 hairless mice. A skin fold in the dorsal region was fixed with two fenestrated titanium plates. A circular wound was made on one side of the skin fold. A metal cylinder with phosphate buffer was fixed into the window of the titanium plate. The concentration of penetrated drug was measured in the buffer. The skin fold was morphologically intact and had a healthy microcirculation. The drug appeared in the acceptor buffer after 30 min, and its concentration exhibited a continuous increase. The presence of ibuprofen was also detected in the plasma. In conclusion, this model allows an exact in vivo study of drug penetration and absorption.

  20. Localizing Ground-Penetrating Radar

    Science.gov (United States)

    2014-11-01

    ing Ground-Penetrating Radar (LGPR) uses very high frequency (VHF) radar reflections of underground features to generate base- line maps and then...Innovative ground- penetrating radar that maps underground geological features provides autonomous vehicles with real-time localization. Localizing...NOV 2014 2. REPORT TYPE 3. DATES COVERED 00-00-2014 to 00-00-2014 4. TITLE AND SUBTITLE Localizing Ground-Penetrating Radar 5a. CONTRACT NUMBER

  1. Nanoparticles skin absorption: New aspects for a safety profile evaluation.

    Science.gov (United States)

    Larese Filon, Francesca; Mauro, Marcella; Adami, Gianpiero; Bovenzi, Massimo; Crosera, Matteo

    2015-07-01

    Nanoparticles (NPs) skin absorption is a wide issue, which needs to be better understood. The attempt of this review is to summarize the scientific evidence concerning open questions, i.e.: the role of NPs intrinsic characteristics (size, shape, charge, surface properties), the penetration of NPs through the intact or impaired skin barrier, the penetration pathways which should be considered and the role of NPs interaction in physiological media. The outcomes suggest that one main difference should be made between metal and non-metal NPs. Both kinds have a secondary NPs size which is given after interaction in physiological media, and allows a size-dependent skin penetration: NPs⩽4nm can penetrate and permeate intact skin, NPs size between 4 and 20nm can potentially permeate intact and damaged skin, NPs size between 21 and 45nm can penetrate and permeate only damaged skin, NPs size>45nm cannot penetrate nor permeate the skin. Other aspects play an important role, mostly for metal NPs, i.e., dissolution in physiological media, which can cause local and systemic effects, the sensitizing or toxic potential and the tendency to create aggregates. This paper suggests a decision tree to evaluate the potential risk for consumers and workers exposed to NPs.

  2. Penetration Tester's Open Source Toolkit

    CERN Document Server

    Faircloth, Jeremy

    2011-01-01

    Great commercial penetration testing tools can be very expensive and sometimes hard to use or of questionable accuracy. This book helps solve both of these problems. The open source, no-cost penetration testing tools presented do a great job and can be modified by the user for each situation. Many tools, even ones that cost thousands of dollars, do not come with any type of instruction on how and in which situations the penetration tester can best use them. Penetration Tester's Open Source Toolkit, Third Edition, expands upon existing instructions so that a professional can get the most accura

  3. Penetration enhancer-containing vesicles (PEVs) as carriers for cutaneous delivery of minoxidil.

    Science.gov (United States)

    Mura, Simona; Manconi, Maria; Sinico, Chiara; Valenti, Donatella; Fadda, Anna Maria

    2009-10-01

    The aim of this work was to evaluate the ability of a few different penetration enhancers to produce elastic vesicles with soy lecithin and the influence of the obtained vesicles on in vitro (trans)dermal delivery of minoxidil. To this purpose, so-called Penetration Enhancer-containing Vesicles (PEVs) were prepared as dehydrated-rehydrated vesicles by using soy lecithin and different amounts of three penetration enhancers, 2-(2-ethoxyethoxy)ethanol (Transcutol), capryl-caproyl macrogol 8-glyceride (Labrasol), and cineole. Soy lecithin liposomes, without penetration enhancers, were used as control. Prepared formulations were characterized in terms of size distribution, morphology, zeta potential, and vesicle deformability. The influence of PEVs on (trans)dermal delivery of minoxidil was studied by in vitro diffusion experiments through newborn pig skin in comparison with traditional liposomes and ethanolic solutions of the drug also containing each penetration enhancer. A skin pre-treatment study using empty PEVs and conventional liposomes was also carried out. Results showed that all the used penetration enhancers were able to give more deformable vesicles than conventional liposomes with a good drug entrapment efficiency and stability. In vitro skin penetration data showed that PEVs were able to give a statistically significant improvement of minoxidil deposition in the skin in comparison with classic liposomes and penetration enhancer-containing drug ethanolic solutions without any transdermal delivery. Moreover, the most deformable PEVs, prepared with Labrasol and cineole, were also able to deliver to the skin a higher total amount of minoxidil than the PE alcoholic solutions thus suggesting that minoxidil delivery to the skin was strictly correlated to vesicle deformability, and therefore to vesicle composition.

  4. Physical Penetration Testing: A Whole New Story in Penetration Testing

    NARCIS (Netherlands)

    Dimkov, Trajce; Pieters, Wolter

    2011-01-01

    Physical penetration testing plays an important role in assuring a company that the security policies are properly enforced and that the security awareness of the employees is on the appropriate level. In physical penetration tests the tester physically enters restricted locations and directly inter

  5. Effect of sodium lauryl sulfate (SLS) on in vitro percutaneous penetration of water, hydrocortisone and nickel

    DEFF Research Database (Denmark)

    Frankild, S; Andersen, Klaus Ejner; Nielsen, Gunnar

    1995-01-01

    as membrane in static in vitro penetration cells. Simultaneous application of SLS together with 1 of the tracer compounds showed, after 48 h, a significant dose-effect relationship between SLS concentration (0.25%, 2% and 10%) and penetration of tritiated water or nickel (p ... or hydrocortisone. Pretreatment of the skin with SLS for 2 h using 3 concentrations (0.25%, 4% and 10%) showed, after 48 h, a significant dose-effect relationship between SLS treatment and penetration of tritiated water or nickel (p .../damaging effect on the skin barrier. It should be kept in mind that the model uses a dead skin membrane without the barrier repair mechanisms of live skin....

  6. Effect of skin tumor properties on laser penetration

    CSIR Research Space (South Africa)

    Karsten, AE

    2009-06-01

    Full Text Available ) λ = 630 nm λ = 680 nm μs (mm-1) μa (mm-1) μt (mm-1) μs (mm-1) μa (mm-1) μt (mm-1) Epidermis 0.79 1.5 0.15 22.86 0.27 23.13 20.95 0.27 21.22 Dermis 0.82 1.4 4 16.94 0.16 17.10 13.33 0.16 13.49 IBCC 0.80 1.4 2 14.25 0.16 14.41 13.0 0... with substantial variation in the laser intensity through the width of the beam. SPIE-OSA Vol. 7373 737316-3 Downloaded from SPIE Digital Library on 06 Oct 2009 to 146.64.81.7. Terms of Use: http://spiedl.org/terms a) In epidermis (z = 0.0133 mm). b...

  7. Fixing the skin barrier: past, present and future--man and dog compared.

    Science.gov (United States)

    Marsella, Rosanna

    2013-02-01

    Skin barrier dysfunction exists in both human and canine atopic dermatitis, leading to increased water loss and potentially facilitating allergen penetration and sensitization. Both lipid (e.g. ceramides) and protein (e.g. filaggrin) abnormalities have been described. Some are genetically inherited (e.g. filaggrin mutations are one of the major risk factors in humans) and some are secondary and linked to inflammation. In humans, numerous studies have shown efficacy of emollients and moisturizers in barrier restoration, and this approach has been for years the mainstay of therapy. Recently, this strategy has shown promise as a preventative function. In veterinary medicine, evidence regarding skin barrier impairment is rapidly building. Decreased ceramides and filaggrin (in some subsets of dogs) have been described. Altered metabolism of ceramides has also been proposed. Despite these preliminary data and the availability of products marketed to improve the skin barrier, evidence regarding the clinical benefit of skin repair intervention is still limited. Preliminary studies have demonstrated that topical application of fatty acids and ceramides and systemic administration of fatty acids improve lipid deficiencies in the skin of dogs with atopic dermatitis, but limited clinical evidence exists. Disease remission in humans is paralleled by an improved skin barrier, both with calcineurin inhibitors and glucocorticoids. In veterinary medicine, a preliminary study on ciclosporin and prednisone failed to detect significant improvement of water loss, while successful immunotherapy correlated with an improved skin barrier. Controlled, large studies are needed to address the question of which skin repair approach is clinically most effective and whether this can be used as a preventative strategy.

  8. Failure Engineered Heavy Metal Penetrators

    Science.gov (United States)

    1992-12-01

    ARMY RESEARCH LABORATORY Failure Engineered Heavy Metal Penetrators, Phase I, SBIR ARL-CR-5· R. Cavalieri, W. Tiarn, and D. Nicholson prepared...REPORT DATE S. REPORT TYPE AND DATES COVERED December 1992 Final Report-1/1/92 - 7/31/92 4. TITLE AND SUBTITLE FAILURE ENGINEERED HEAVY METAL PENETRATORS

  9. Electromagnetic Field Penetration Studies

    Science.gov (United States)

    Deshpande, M.D.

    2000-01-01

    A numerical method is presented to determine electromagnetic shielding effectiveness of rectangular enclosure with apertures on its wall used for input and output connections, control panels, visual-access windows, ventilation panels, etc. Expressing EM fields in terms of cavity Green's function inside the enclosure and the free space Green's function outside the enclosure, integral equations with aperture tangential electric fields as unknown variables are obtained by enforcing the continuity of tangential electric and magnetic fields across the apertures. Using the Method of Moments, the integral equations are solved for unknown aperture fields. From these aperture fields, the EM field inside a rectangular enclosure due to external electromagnetic sources are determined. Numerical results on electric field shielding of a rectangular cavity with a thin rectangular slot obtained using the present method are compared with the results obtained using simple transmission line technique for code validation. The present technique is applied to determine field penetration inside a Boeing-757 by approximating its passenger cabin as a rectangular cavity filled with a homogeneous medium and its passenger windows by rectangular apertures. Preliminary results for, two windows, one on each side of fuselage were considered. Numerical results for Boeing-757 at frequencies 26 MHz, 171-175 MHz, and 428-432 MHz are presented.

  10. Top Sounder Ice Penetration

    Science.gov (United States)

    Porter, D. L.; Goemmer, S. A.; Sweeney, J. H.

    2014-12-01

    Ice draft measurements are made as part of normal operations for all US Navy submarines operating in the Arctic Ocean. The submarine ice draft data are unique in providing high resolution measurements over long transects of the ice covered ocean. The data has been used to document a multidecadal drop in ice thickness, and for validating and improving numerical sea-ice models. A submarine upward-looking sonar draft measurement is made by a sonar transducer mounted in the sail or deck of the submarine. An acoustic beam is transmitted upward through the water column, reflecting off the bottom of the sea ice and returning to the transducer. Ice thickness is estimated as the difference between the ship's depth (measured by pressure) and the acoustic range to the bottom of the ice estimated from the travel time of the sonar pulse. Digital recording systems can provide the return off the water-ice interface as well as returns that have penetrated the ice. Typically, only the first return from the ice hull is analyzed. Information regarding ice flow interstitial layers provides ice age information and may possibly be derived with the entire return signal. The approach being investigated is similar to that used in measuring bottom sediment layers and will involve measuring the echo level from the first interface, solving the reflection loss from that transmission, and employing reflection loss versus impedance mismatch to ascertain ice structure information.

  11. An Earth Penetrating Modeling Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Stokes, E; Yarrington, P; Glenn, L

    2005-06-21

    Documentation of a study to assess the capability of computer codes to predict lateral loads on earth penetrating projectiles under conditions of non-normal impact. Calculations simulated a set of small scale penetration tests into concrete targets with oblique faces at angles of 15 and 30 degrees to the line-of-flight. Predictive codes used by the various calculational teams cover a wide range of modeling approaches from approximate techniques, such as cavity expansion, to numerical methods, such as finite element codes. The modeling assessment was performed under the auspices of the Phenomenology Integrated Product Team (PIPT) for the Robust Nuclear Earth Penetrator Program (RNEP). Funding for the penetration experiments and modeling was provided by multiple earth penetrator programs.

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

    Science.gov (United States)

    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.

  13. Penetration dynamics of a magnetic field pulse into high-? superconductors

    Science.gov (United States)

    Meerovich, V.; Sinder, M.; Sokolovsky, V.; Goren, S.; Jung, G.; Shter, G. E.; Grader, G. S.

    1996-12-01

    The penetration of a magnetic field pulse into a high-0953-2048/9/12/004/img9 superconducting plate is investigated experimentally and theoretically. It follows from our experiments that the threshold of penetration increases with increasing amplitude and/or decreasing duration of the applied pulse. The penetrating field continues to grow as the applied magnetic field decreases. The peculiarities observed are explained in the framework of the extended critical state model. It appears that the deviations from Bean's classical critical state model are characterized by a parameter equal to the square of the ratio of plate thickness to skin depth. The applicability of the classical critical state model is restricted by the condition that this parameter is much less than 1. This condition is also the criterion for the applicability of pulse methods of critical current measurements.

  14. Electrochemical monitoring of native catalase activity in skin using skin covered oxygen electrode.

    Science.gov (United States)

    Nocchi, Sarah; Björklund, Sebastian; Svensson, Birgitta; Engblom, Johan; Ruzgas, Tautgirdas

    2017-07-15

    A skin covered oxygen electrode, SCOE, was constructed with the aim to study the enzyme catalase, which is part of the biological antioxidative system present in skin. The electrode was exposed to different concentrations of H2O2 and the amperometric current response was recorded. The observed current is due to H2O2 penetration through the outermost skin barrier (referred to as the stratum corneum, SC) and subsequent catalytic generation of O2 by catalase present in the underlying viable epidermis and dermis. By tape-stripping the outermost skin layers we demonstrate that SC is a considerable diffusion barrier for H2O2 penetration. Our experiments also indicate that skin contains a substantial amount of catalase, which is sufficient to detoxify H2O2 that reaches the viable epidermis after exposure of skin to high concentrations of peroxide (0.5-1mM H2O2). Further, we demonstrate that the catalase activity is reduced at acidic pH, as compared with the activity at pH 7.4. Finally, experiments with often used penetration enhancer thymol shows that this compound interferes with the catalase reaction. Health aspect of this is briefly discussed. Summarizing, the results of this work show that the SCOE can be utilized to study a broad spectrum of issues involving the function of skin catalase in particular, and the native biological antioxidative system in skin in general. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Theory of activated penetrant diffusion in viscous fluids and colloidal suspensions.

    Science.gov (United States)

    Zhang, Rui; Schweizer, Kenneth S

    2015-10-14

    We heuristically formulate a microscopic, force level, self-consistent nonlinear Langevin equation theory for activated barrier hopping and non-hydrodynamic diffusion of a hard sphere penetrant in very dense hard sphere fluid matrices. Penetrant dynamics is controlled by a rich competition between force relaxation due to penetrant self-motion and collective matrix structural (alpha) relaxation. In the absence of penetrant-matrix attraction, three activated dynamical regimes are predicted as a function of penetrant-matrix size ratio which are physically distinguished by penetrant jump distance and the nature of matrix motion required to facilitate its hopping. The penetrant diffusion constant decreases the fastest with size ratio for relatively small penetrants where the matrix effectively acts as a vibrating amorphous solid. Increasing penetrant-matrix attraction strength reduces penetrant diffusivity due to physical bonding. For size ratios approaching unity, a distinct dynamical regime emerges associated with strong slaving of penetrant hopping to matrix structural relaxation. A crossover regime at intermediate penetrant-matrix size ratio connects the two limiting behaviors for hard penetrants, but essentially disappears if there are strong attractions with the matrix. Activated penetrant diffusivity decreases strongly with matrix volume fraction in a manner that intensifies as the size ratio increases. We propose and implement a quasi-universal approach for activated diffusion of a rigid atomic/molecular penetrant in a supercooled liquid based on a mapping between the hard sphere system and thermal liquids. Calculations for specific systems agree reasonably well with experiments over a wide range of temperature, covering more than 10 orders of magnitude of variation of the penetrant diffusion constant.

  16. Theory of activated penetrant diffusion in viscous fluids and colloidal suspensions

    Science.gov (United States)

    Zhang, Rui; Schweizer, Kenneth S.

    2015-10-01

    We heuristically formulate a microscopic, force level, self-consistent nonlinear Langevin equation theory for activated barrier hopping and non-hydrodynamic diffusion of a hard sphere penetrant in very dense hard sphere fluid matrices. Penetrant dynamics is controlled by a rich competition between force relaxation due to penetrant self-motion and collective matrix structural (alpha) relaxation. In the absence of penetrant-matrix attraction, three activated dynamical regimes are predicted as a function of penetrant-matrix size ratio which are physically distinguished by penetrant jump distance and the nature of matrix motion required to facilitate its hopping. The penetrant diffusion constant decreases the fastest with size ratio for relatively small penetrants where the matrix effectively acts as a vibrating amorphous solid. Increasing penetrant-matrix attraction strength reduces penetrant diffusivity due to physical bonding. For size ratios approaching unity, a distinct dynamical regime emerges associated with strong slaving of penetrant hopping to matrix structural relaxation. A crossover regime at intermediate penetrant-matrix size ratio connects the two limiting behaviors for hard penetrants, but essentially disappears if there are strong attractions with the matrix. Activated penetrant diffusivity decreases strongly with matrix volume fraction in a manner that intensifies as the size ratio increases. We propose and implement a quasi-universal approach for activated diffusion of a rigid atomic/molecular penetrant in a supercooled liquid based on a mapping between the hard sphere system and thermal liquids. Calculations for specific systems agree reasonably well with experiments over a wide range of temperature, covering more than 10 orders of magnitude of variation of the penetrant diffusion constant.

  17. Theory of activated penetrant diffusion in viscous fluids and colloidal suspensions

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Rui; Schweizer, Kenneth S., E-mail: kschweiz@illinois.edu [Department of Materials Science and Frederick Seitz Materials Research Laboratory, University of Illinois, 1304 West Green Street, Urbana, Illinois 61801 (United States)

    2015-10-14

    We heuristically formulate a microscopic, force level, self-consistent nonlinear Langevin equation theory for activated barrier hopping and non-hydrodynamic diffusion of a hard sphere penetrant in very dense hard sphere fluid matrices. Penetrant dynamics is controlled by a rich competition between force relaxation due to penetrant self-motion and collective matrix structural (alpha) relaxation. In the absence of penetrant-matrix attraction, three activated dynamical regimes are predicted as a function of penetrant-matrix size ratio which are physically distinguished by penetrant jump distance and the nature of matrix motion required to facilitate its hopping. The penetrant diffusion constant decreases the fastest with size ratio for relatively small penetrants where the matrix effectively acts as a vibrating amorphous solid. Increasing penetrant-matrix attraction strength reduces penetrant diffusivity due to physical bonding. For size ratios approaching unity, a distinct dynamical regime emerges associated with strong slaving of penetrant hopping to matrix structural relaxation. A crossover regime at intermediate penetrant-matrix size ratio connects the two limiting behaviors for hard penetrants, but essentially disappears if there are strong attractions with the matrix. Activated penetrant diffusivity decreases strongly with matrix volume fraction in a manner that intensifies as the size ratio increases. We propose and implement a quasi-universal approach for activated diffusion of a rigid atomic/molecular penetrant in a supercooled liquid based on a mapping between the hard sphere system and thermal liquids. Calculations for specific systems agree reasonably well with experiments over a wide range of temperature, covering more than 10 orders of magnitude of variation of the penetrant diffusion constant.

  18. Penetration profile of microspheres in follicular targeting of terminal hair follicles.

    Science.gov (United States)

    Toll, R; Jacobi, U; Richter, H; Lademann, J; Schaefer, H; Blume-Peytavi, U

    2004-07-01

    The transfollicular administration of pharmacologically active molecules is of current therapeutic interest, mainly with regard to delivery to specific sites of the hair follicle (HF) and the reduction of hepatic metabolism and systemic toxicity. HF are privileged pathways for specific molecules depending on formulations, which enter faster into these shunts than through the stratum corneum. The aim was to optimize the delivery of fluorescent microspheres into the HF, thereby, developing a standardized protocol for follicular targeting with microspheres. The number of HF showing penetration, as well as the depth of penetration, was determined. Freshly excised skin samples with terminal HF were divided into groups, with or without prior treatment with cyanoacrylate skin surface stripping-technique (CSSS). Thereafter microspheres at a size of 0.75-6.0 microm were applied according to the developed standardized protocol. Skin biopsies were obtained, shock-frozen, and sectioned in 5 microm slices. We demonstrated a selective penetration route of the microspheres into the HF. Optimal microsphere size proved to be approximately 1.5 microm, with a 55% rate of all HF, and with a maximum penetration depth of >2300 microm. Without previous CSSS treatment of the skin, the transfollicular microsphere penetration was below 27% with a maximum penetration depth of 1000 microm. Thus, the basis for follicular targeting of essential structures containing stem cells for keratinocytes, melanocytes, and mast cells has been laid.

  19. Evaluation of the in vitro skin permeation of antiviral drugs from penciclovir 1% cream and acyclovir 5% cream used to treat herpes simplex virus infection

    Directory of Open Access Journals (Sweden)

    Bader Marlene

    2009-04-01

    Full Text Available Abstract Background Herpes simplex virus infection (HSV is a common and ubiquitous infection of the skin which causes mucocutaneous lesions called cold sores (herpes labialis or fever blisters. It is estimated that approximately 80% of the population worldwide are carriers of the Herpes simplex virus, approximately 40% suffer from recurrent recurrent infections. This study evaluates the in vitro skin permeation and penetration of penciclovir and acyclovir from commercialized creams for the treatment of herpes labialis (cold sores, using non viable excised human abdominal skin samples, which were exposed to 5 mg/cm2 of acyclovir 5% cream or penciclovir 1% cream. Methods After 24 h of cream application, excess cream was washed off and layers of stratum corneum were removed by successive tape stripping. Amounts of active ingredients having penetrated through the skin were measured, as well as the amounts in the washed-off cream, in skin strips and creams remaining in the skin. Molecular modelling was used to evaluate physico-chemical differences between the drugs. Western blot analysis enabled to determine whether the marker of basal cells keratin 5 could be detected in the various tape strips. Results Application of penciclovir 1% cream yielded higher concentration of drug in the deeper layers of the epidermis as well as a higher drug flux through the skin. Molecular modelling showed two higher hydrophobic moieties for acyclovir. Presence of the basal cell marker keratin 5 was underscored in the deeper tape strips from the skin, giving evidence that both drugs can reach their target cells. Conclusion Penciclovir 1% cream has the tendency to facilitate the diffusion of the drug through the stratum corneum into the deeper epidermis layers, in which it could reach the target basal cells at effective therapeutical concentration. The small difference in the surface properties between both molecules might also contribute to favour the passage of

  20. Oily skin

    Science.gov (United States)

    ... keep your skin clean using warm water and soap, or a soapless cleanser. Clean your face with astringent pads if frequent face washing causes irritation. Use only water-based or oil-free cosmetics if you have oily skin. Your ...

  1. Your Skin

    Science.gov (United States)

    ... your body. Without skin, people's muscles, bones, and organs would be hanging out all over the place. Skin holds everything together. It also: protects our bodies helps keep our bodies at just the right temperature allows us to have the sense of touch Don't Miss Your Epidermis The ...

  2. Ex vivo cutaneous penetration of econazole nitrate from SLN incorporated in hydrophilic gels

    OpenAIRE

    Canu, Giacomina; Sanna, Vanna Annunziata; Gavini, Elisabetta; Cossu, Massimo; Rassu, Giovanna; Giunchedi, Paolo

    2006-01-01

    Solid lipid nanoparticles (SLN) are considered as innovative drug carrier for topical application. The small size of the lipid particles ensures close contact to the stratum corneum and can increase the amount of the drug penetrating into the skin and it allows controlled drug release. The aim of this study was to develop controlled release gels containing SLN dispersions loaded with Econazole Nitrate (ECN) and to evaluate ex vivo skin penetration of the drug released from t...

  3. Physical Penetration Testing: A Whole New Story in Penetration Testing

    OpenAIRE

    2011-01-01

    Physical penetration testing plays an important role in assuring a company that the security policies are properly enforced and that the security awareness of the employees is on the appropriate level. In physical penetration tests the tester physically enters restricted locations and directly interacts with the employees to convince them to break a policy or provide credentials. The physical access and the direct interaction with the employees complicate the execution of the tests and have e...

  4. Topical Nano and Microemulsions for Skin Delivery

    Directory of Open Access Journals (Sweden)

    Christofori M. R. R. Nastiti

    2017-09-01

    Full Text Available Nanosystems such as microemulsions (ME and nanoemulsions (NE offer considerable opportunities for targeted drug delivery to and via the skin. ME and NE are stable colloidal systems composed of oil and water, stabilised by a mixture of surfactants and cosurfactants, that have received particular interest as topical skin delivery systems. There is considerable scope to manipulate the formulation components and characteristics to achieve optimal bioavailability and minimal skin irritancy. This includes the incorporation of established chemical penetration enhancers to fluidize the stratum corneum lipid bilayers, thus reducing the primary skin barrier and increasing permeation. This review discusses nanosystems with utility in skin delivery and focuses on the composition and characterization of ME and NE for topical and transdermal delivery. The mechanism of skin delivery across the stratum corneum and via hair follicles is reviewed with particular focus on the influence of formulation.

  5. Nanocarriers for skin delivery of cosmetic antioxidants

    Directory of Open Access Journals (Sweden)

    Lucia Montenegro

    2014-08-01

    Full Text Available The demand of natural skin care products is steadily growing since consumers perceive them as safe. Currently, cosmetic manufacturers are focusing their efforts on developing innovative natural products to address skin-aging signs, thus meeting consumers’ needs of healthy appearance and well-being. To prevent or treat skin aging, topical supplementation with antioxidant is regarded as one of the most promising strategies. However, most antioxidants presently used in skin care formulations show unfavorable physicochemical properties such as excessive lipophilicity or hydrophilicity, chemical instability and poor skin penetration that actively limit their effectiveness after topical application. Therefore, nanocarriers such as liposomes, niosomes, microemulsions and nanoparticles have been widely investigated as delivery systems for antioxidants to improve their beneficial effects in the treatment of skin aging. In this article, the antioxidants most commonly used in anti-aging cosmetic products will be reviewed along with the nanocarriers designed to improve their safety and effectiveness.

  6. Skin-inspired electronic devices

    Directory of Open Access Journals (Sweden)

    Alex Chortos

    2014-09-01

    Full Text Available Electronic devices that mimic the properties of skin have potential important applications in advanced robotics, prosthetics, and health monitoring technologies. Methods for measuring tactile and temperature signals have progressed rapidly due to innovations in materials and processing methods. Imparting skin-like stretchability to electronic devices can be accomplished by patterning traditional electronic materials or developing new materials that are intrinsically stretchable. The incorporation of sensing methods with transistors facilitates large-area sensor arrays. While sensor arrays have surpassed the properties of human skin in terms of sensitivity, time response, and device density, many opportunities remain for future development.

  7. Facilitering som styringsredskab

    OpenAIRE

    Jørgensen, Karen Overgaard

    2006-01-01

    #This thesis surveys facilitation as a new tool of steering within the public sector in Denmark. It is explored how facilitation is articulated and practiced among facilitators from the public, private and voluntary sector. Furthermore, the facilitator’s challenges by using facilitation are examined. The thesis is based on the presumption that facilitation is articulated by rationalities, which influence how facilitation is practiced and performed. Also, a facilitator is seen as a performer a...

  8. Compound antimalarial ethosomal cataplasm: preparation, evaluation, and mechanism of penetration enhancement

    Directory of Open Access Journals (Sweden)

    Shen S

    2015-06-01

    Full Text Available Shuo Shen, Shu-Zhi Liu, Yu-Shi Zhang, Mao-Bo Du, Ai-Hua Liang, Li-Hua Song, Zu-Guang Ye Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China Abstract: Malaria is still a serious public health problem in some parts of the world. The problems of recurrence and drug resistance are increasingly more serious. Thus, it is necessary to develop a novel antimalarial agent. The objectives of this study were to construct a novel compound antimalarial transdermal nanosystem–ethosomal cataplasm, to investigate its characteristics and efficiency, and to systematically explore the penetration-enhancing mechanisms of ethosomal cataplasm. Artesunate-loaded ethosomes and febrifugine-loaded ethosomes were prepared, and their characteristics were evaluated. Drug-loaded ethosomes were incorporated in the matrix of cataplasm to form the compound antimalarial ethosomal cataplasm. With the help of ethosomal technology, the accumulated permeation quantity of artesunate significantly increased at 8 hours after administration, which was 1.57 times as much as that of conventional cataplasm. Soon after administration, the ethosomal cataplasm could make a large quantity of antimalarial drug quickly penetrate through skin, then the remaining drug in the ethosomal cataplasm could be steadily released. These characteristics of ethosomal cataplasm are favorable for antimalarial drugs to kill Plasmodium spp. quickly and prevent the resurgence of Plasmodium spp. As expected, the ethosomal cataplasm showed good antimalarial efficiency in this experiment. The negative conversion rates were 100% and the recurrence rates were 0% at all dosages. The mechanism of penetration enhancement of the ethosomal cataplasm was systematically explored using an optics microscope, polarization microscope, and transmission electron microscopy. The microstructure, ultrastructure, and birefringent structure in skin were observed. Data

  9. Cement penetration after patella venting.

    Science.gov (United States)

    Jones, Christopher W; Lam, Li-On; Butler, Adam; Wood, David J; Walsh, William R

    2009-01-01

    There is a high rate of patellofemoral complications following total knee arthroplasty. Optimization of the cement-bone interface by venting and suction of the tibial plateau has been shown to improve cement penetration. Our study was designed to investigate if venting the patella prior to cementing improved cement penetration. Ten paired cadaver patellae were allocated prior to resurfacing to be vented or non-vented. Bone mineral density (BMD) was measured by DEXA scanning. In vented specimens, a 1.6 mm Kirschner wire was used to breach the anterior cortex at the center. Specimens were resurfaced with standard Profix instrumentation and Versabond bone cement (Smith and Nephew PLC, UK). Cement penetration was assessed from Faxitron and sectioned images by a digital image software package (ImageJ V1.38, NIH, USA). Wilcoxon rank sum test was used to assess the difference in cement penetration between groups. The relationship between BMD and cement penetration was analyzed by Pearson correlation coefficient. There was a strong negative correlation between peak BMD and cement penetration when analyzed independent of experimental grouping (r(2)=-0.812, p=0.004). Wilcoxon rank sum testing demonstrated no significant difference (rank sum statistic W=27, p=0.579) in cement penetration between vented (10.53%+/-4.66; mean+/-std dev) and non-vented patellae (11.51%+/-6.23; mean+/-std dev). Venting the patella using a Kirschner wire does not have a significant effect on the amount of cement penetration achieved in vitro using Profix instrumentation and Versabond cement.

  10. Is Color Experience Cognitively Penetrable?

    Science.gov (United States)

    Brogaard, Berit; Gatzia, Dimitria E

    2017-01-01

    Is color experience cognitively penetrable? Some philosophers have recently argued that it is. In this paper, we take issue with the claim that color experience is cognitively penetrable. We argue that the notion of cognitive penetration that has recently dominated the literature is flawed since it fails to distinguish between the modulation of perceptual content by non-perceptual principles and genuine cognitive penetration. We use this distinction to show that studies suggesting that color experience can be modulated by factors of the cognitive system do not establish that color experience is cognitively penetrable. Additionally, we argue that even if color experience turns out to be modulated by color-related beliefs and knowledge beyond non-perceptual principles, it does not follow that color experience is cognitively penetrable since the experiences of determinate hues involve post-perceptual processes. We conclude with a brief discussion of the implications that these ideas may have on debates in philosophy. Copyright © 2016 Cognitive Science Society, Inc.

  11. Development of an Active Topical Skin Protectant (aTSP)

    Science.gov (United States)

    2016-02-01

    topical protectant to vulnerable skin surfaces prior to entry into a chemical combat arena was proposed as a protective measure against percutaneous...candidate formulations. The initial analytical method developed for evaluating the effectiveness of TSPs against penetration by HD used Fourier...Several evaluation techniques, including bioengineering analytical technologies, were used to evaluate skin damage under several protocols. Methods

  12. Topical Delivery of Hyaluronic Acid into Skin using SPACE-peptide Carriers

    Science.gov (United States)

    Chen, Ming; Gupta, Vivek; Anselmo, Aaron C.; Muraski, John A.; Mitragotri, Samir

    2014-01-01

    Topical penetration of macromolecules into skin is limited by their low permeability. Here, we report the use of a skin penetrating peptide, SPACE peptide, to enhance topical delivery of a macromolecule, hyaluronic acid (HA, MW: 200–325 kDa). The peptide was conjugated to phospholipids and used to prepare an ethosomal carrier system (~110 nm diameter), encapsulating HA. The SPACE-ethosomal system (SES) enhanced HA penetration into porcine skin in vitro by 7.8+/−1.1-fold compared to PBS. The system also enhanced penetration of HA in human skin in vitro, penetrating deep into the epidermis and dermis in skin of both species. In vivo experiments performed using SKH1 hairless mice also confirmed increased dermal penetration of HA using the delivery system; a 5-fold enhancement in penetration was found compared to PBS control. Concentrations of HA in skin were about 1000-fold higher than those in blood; confirming the localized nature of HA delivery into skin. The SPACE-ethosomal delivery system provides a formulation for topical delivery of macromolecules that are otherwise difficult to deliver into skin. PMID:24129342

  13. Mucus-penetrating nanoparticles for vaginal and gastrointestinal drug delivery

    Science.gov (United States)

    Ensign-Hodges, Laura

    A method that could provide more uniform and longer-lasting drug delivery to mucosal surfaces holds the potential to greatly improve the effectiveness of prophylactic and therapeutic approaches for numerous diseases and conditions, including sexually transmitted infections and inflammatory bowel disease. However, the body's natural defenses, including adhesive, rapidly cleared mucus linings coating nearly all entry points to the body not covered by skin, has limited the effectiveness of drug and gene delivery by nanoscale delivery systems. Here, we investigate the use of muco-inert mucus-penetrating nanoparticles (MPP) for improving vaginal and gastrointestinal drug delivery. Conventional hydrophobic nanoparticles strongly adhere to mucus, facilitating rapid clearance from the body. Here, we demonstrate that mucoadhesive polystyrene nanoparticles (conventional nanoparticles, CP) become mucus-penetrating in human cervicovaginal mucus (CVM) after pretreatment with sufficient concentrations of Pluronic F127. Importantly, the diffusion rate of large MPP did not change in F127 pretreated CVM, implying there is no affect on the native pore structure of CVM. Additionally, there was no increase in inflammatory cytokine release in the vaginal tract of mice after daily application of 1% F127 for one week. Importantly, HSV virus remains adherent in F127-pretreated CVM. Mucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that hypotonically-induced fluid uptake could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We evaluated hypotonic formulations for delivering water-soluble drugs and for drug delivery with MPP. Hypotonic formulations markedly increased the rate at which drugs and MPP reached the epithelial surface. Additionally, hypotonic formulations greatly enhanced drug and MPP delivery to the entire epithelial surface, including deep into the vaginal folds (rugae) that isotonic formulations

  14. A Miniature Probe for Ultrasonic Penetration of a Single Cell

    Directory of Open Access Journals (Sweden)

    Mingfei Xiao

    2009-05-01

    Full Text Available Although ultrasound cavitation must be avoided for safe diagnostic applications, the ability of ultrasound to disrupt cell membranes has taken on increasing significance as a method to facilitate drug and gene delivery. A new ultrasonic resonance driving method is introduced to penetrate rigid wall plant cells or oocytes with springy cell membranes. When a reasonable design is created, ultrasound can gather energy and increase the amplitude factor. Ultrasonic penetration enables exogenous materials to enter cells without damaging them by utilizing instant acceleration. This paper seeks to develop a miniature ultrasonic probe experiment system for cell penetration. A miniature ultrasonic probe is designed and optimized using the Precise Four Terminal Network Method and Finite Element Method (FEM and an ultrasonic generator to drive the probe is designed. The system was able to successfully puncture a single fish cell.

  15. Aging skin.

    Science.gov (United States)

    Bolognia, J L

    1995-01-16

    Aging of the skin is a composite of actinic damage, chronologic aging, and hormonal influences. The majority of changes associated with aging, such as wrinkles and solar lentigines ("liver spots"), are due to photoaging and reflect cumulative sun exposure as well as skin pigmentation. Classically, chronologic aging includes those cutaneous changes that occur in non-sun-exposed areas, such as the buttocks, and are observed in both men and women. A clinical example would be soft tissue sagging due to elastic fiber degeneration. In women, investigations into the effect of hormones on aging of the skin have concentrated on estrogens; in men, there have been a limited number of studies on the influence of testosterone. The latter have shown an age-dependent decrease in tissue androgens in pubic skin, but not scrotal or thigh skin. To date, age has not been shown to have an effect on androgen receptor binding, although a decrease in foreskin 5 alpha-reductase activity with increasing age has been described. In fibroblast cultures from foreskins, there have been conflicting results as to whether 5 alpha-reductase activity decreases in an age-dependent manner. Some of the skin changes that have been categorized as secondary to chronologic aging, such as decreased sebaceous gland activity and decreased hair growth, may actually represent a decline in the concentration of tissue androgens with increasing age. The influence of androgens on age-related changes in keratinocyte and fibroblast function remains speculative.

  16. Topical Delivery of Protein and Peptide Using Novel Cell Penetrating Peptide IMT-P8

    Science.gov (United States)

    Gautam, Ankur; Nanda, Jagpreet Singh; Samuel, Jesse S.; Kumari, Manisha; Priyanka, Priyanka; Bedi, Gursimran; Nath, Samir K.; Mittal, Garima; Khatri, Neeraj; Raghava, Gajendra Pal Singh

    2016-01-01

    Skin, being the largest organ of the body, is an important site for drug administration. However, most of the drugs have poor permeability and thus drug delivery through the skin is very challenging. In this study, we examined the transdermal delivery capability of IMT-P8, a novel cell-penetrating peptide. We generated IMT-P8-GFP and IMT-P8-KLA fusion constructs and evaluated their internalization into mouse skin after topical application. Our results demonstrate that IMT-P8 is capable of transporting green fluorescent protein (GFP) and proapoptotic peptide, KLA into the skin and also in different cell lines. Interestingly, uptake of IMT-P8-GFP was considerably higher than TAT-GFP in HeLa cells. After internalization, IMT-P8-KLA got localized to the mitochondria and caused significant cell death in HeLa cells signifying an intact biological activity. Further in vivo skin penetration experiments revealed that after topical application, IMT-P8 penetrated the stratum corneum, entered into the viable epidermis and accumulated inside the hair follicles. In addition, both IMT-P8-KLA and IMT-P8-GFP internalized into the hair follicles and dermal tissue of the skin following topical application. These results suggested that IMT-P8 could be a potential candidate to be used as a topical delivery vehicle for various cosmetic and skin disease applications. PMID:27189051

  17. The release and transdermal penetration of baclofen formulated in a poloxamer lecithin organogel.

    Science.gov (United States)

    Arnold, John J; Asbill, Scott

    2009-01-01

    The purpose of this study was to evaluate the in vitro release and ex vivo penetration of baclofen following incorporation into a 2% poloxamer lecithin organogel. Franz cells were utilized for both the release and penetration studies. Semi-permeable dialysis membranes were used as the model skin for the penetration study. Baclofen release and penetration at predetermined time points were assessed using high-performamce liquid chromatographic analysis. Results demonstrated that baclofen release from the poloxamer lecithin organogel was significantly higher than its penetration through porcine skin. The amount of baclofen released by the poloxamer lecithin organogel was linear up to 12 hours. Approximately 20% of applied drug was released over the duration of the study period. In comparison with drug released, the ex vivo penetration of baclofen through porcine skin was very low with only minute detectable quantities (significantly less than 1%) after the 12-hour study period. These results suggest that the request to include baclofen into a compounded poloxamer lecithin organogel should be approached cautiously by compounding pharmacists.

  18. Personnel decontamination and preventive skin care; Personendekontamination und Hautprophylaxe

    Energy Technology Data Exchange (ETDEWEB)

    Henning, Klaus; Gojowczyk, Peter [AKA Kunz GmbH, Waldenbuch (Germany)

    2010-07-15

    Skin contamination arises from contact with contaminated aqueous solutions and from transmission of radioactively contaminated dirt particles. As long as the surface of the skin is neither inflamed nor showing any lesions, normally only a limited part of the top layer (epidermis), i.e. the upper layers of the stratum corneum, is contaminated. The intact horny layer has a barrier function protecting against the penetration of chemicals and dirt particles. The horny layer can be damaged by water, solvents, alkaline substances, and acids. In general, it is safe to say that the horny layer acts as a natural barrier to the penetration of liquid and particulate impurities into lower layers of the skin. As long as the horny layer is intact and free from lesions, the risk of incorporation can be considered low. When decontaminating and cleansing the skin, also in daily skin cleansing, care must be taken to prevent the acid protective layer and the horny layer from being compromised. Daily cleansing and cleansing for decontamination must be carried out with a mild, weakly acidic detergent. In addition, prevention should be achieved daily by applying a non-greasy skin lotion to protect the skin. Following a systematic regular regimen in skin cleansing and preventive skin care as well as a specific approach in skin decontamination and cleansing will avoid damage to the skin and remove any contamination incurred. This approach comprises a three-pronged concept, namely skin protection, cleansing and care. (orig.)

  19. Skin Cancer Prevention

    Science.gov (United States)

    ... Genetics of Skin Cancer Skin Cancer Screening Research Skin Cancer Prevention (PDQ®)–Patient Version What is prevention? ... prevent cancer are being studied. General Information About Skin Cancer Key Points Skin cancer is a disease ...

  20. Skin Cancer Screening

    Science.gov (United States)

    ... Genetics of Skin Cancer Skin Cancer Screening Research Skin Cancer Screening (PDQ®)–Patient Version What is screening? ... These are called diagnostic tests . General Information About Skin Cancer Key Points Skin cancer is a disease ...

  1. Dry Skin Relief

    Science.gov (United States)

    ... Advocacy priorities AADA Health System Reform Principles Drug pricing and availability CVS dermatologic formulary restrictions Access to ... Skin care for men Skin care on a budget Skin care products Skin care secrets Skin of ...

  2. Efficacy of skin wash on dermal absorption: an in vitro study on four model compounds of varying solubility

    DEFF Research Database (Denmark)

    Nielsen, Jesper Bo

    2010-01-01

    that percutaneous penetration continues after end of exposure due to the reservoir present in the skin. However, penetration rate will decrease significantly, and it is evident that simple hand-wash after end of exposure not only reduces the amount of residue present in the upper skin compartment but also......PURPOSE: Following dermal exposure to chemicals causing systemic toxicity, the general advice to avoid further systemic exposure is to wash the skin. The present study uses four model compounds (benzoic acid, glyphosat, caffeine, malathion) with varying size and solubility to substantiate...... this advice and quantify the effect of skin wash following 6 h dermal exposure on subsequent extent of skin penetration and deposition within the skin compartment. METHOD: Percutaneous penetration through human skin is studied in an in vitro model with static diffusion cells. RESULTS: The study demonstrates...

  3. Serotonin in human skin

    Institute of Scientific and Technical Information of China (English)

    Jianguo Huang; Qiying Gong; Guiming Li

    2005-01-01

    In this review the authors summarize data of a potential role for serotonin in human skin physiology and pathology. The uncovering of endogenous serotonin synthesis and its transformation to melatonin underlines a putative important role of this pathway in melanocyte physiology and pathology. Pathways of the biosynthesis and biodegradation of serotonin have been characterized in human beings and its major cellular populations. Moreover, receptors of serotonin are expressed on keratinocytes, melanocytes, and fibroblasts and these mediate phenotypic actions on cellular proliferation and differentiation. And the widespread expression of a cutaneous seorotoninergic system indicates considerable selectivity of action to facilitate intra-, auto-, or paracrine mechanisms that define and influence skin function in a highly compartmentalized manner. Melatonin, in turn, can also act as a hormone, neurotransmitter, cytokine, biological modifier and immunomodulator. Thus, Serotonin local synthesis and cellular localization could thus become of great importance in the diagnosis and management of cutaneous pathology.

  4. Microplasma effect on skin scaffold for melanoma cancer treatment

    Science.gov (United States)

    Abdullah, Zulaika; Zaaba, S. K.; Mustaffa, M. T.; Mohamad, C. W. S. R.; Zakaria, A.

    2017-03-01

    An atmospheric plasma system using Helium gas was developed. The effect of helium plasma treatment on skin scaffold surface was studied by scanning electron microscopy (SEM). The changes of skin scaffold surfaces before and after helium plasma treatment was recorded. The surface of skin scaffold changed with the prolonged of helium plasma treatment time. The depth of helium plasma penetration was studied using methylene blue dye staining method. The methylene blue will detect the presence or absence of an oxygen that was induced from plasma excitation. The presence of the oxygen indicated on the depth of helium plasma penetration. Results showed plasma are able to penetrate 4mm of skin scaffold after 1200 seconds of exposure.

  5. Comparison of skin decontamination efficacy of commercial decontamination products following exposure to VX on human skin.

    Science.gov (United States)

    Thors, L; Koch, M; Wigenstam, E; Koch, B; Hägglund, L; Bucht, A

    2017-08-01

    The decontamination efficacy of four commercially available skin decontamination products following exposure to the nerve agent VX was evaluated in vitro utilizing a diffusion cell and dermatomed human skin. The products included were Reactive Skin Decontamination Lotion (RSDL), the Swedish decontamination powder 104 (PS104), the absorbent Fuller's Earth and the aqueous solution alldecontMED. In addition, various decontamination procedures were assessed to further investigate important mechanisms involved in the specific products, e.g. decontamination removal from skin, physical removal by sponge swabbing and activation of degradation mechanisms. The efficacy of each decontamination product was evaluated 5 or 30 min after dermal application of VX (neat or diluted to 20% in water). The RSDL-lotion was superior in reducing the penetration of VX through human skin, both when exposed as neat agent and when diluted to 20% in water. Swabbing with the RSDL-sponge during 2 min revealed decreased efficacy compared to applying the RSDL-lotion directly on the skin for 30 min. Decontamination with Fuller's Earth and alldecontMED significantly reduced the penetration of neat concentration of VX through human skin. PS104-powder was insufficient for decontamination of VX at both time-points, independently of the skin contact time of PS104. The PS104-slurry (a mixture of PS104-powder and water), slightly improved the decontamination efficacy. Comparing the time-points for initiated decontamination revealed less penetrated VX for RSDL and Fuller's Earth when decontamination was initiated after 5 min compared to 30 min post-exposure, while alldecontMED displayed similar efficacy at both time-points. Decontamination by washing with water only resulted in a significant reduction of penetrated VX when washing was performed 5 min after exposure, but not when decontamination was delayed to 30 min post-exposure of neat VX. In conclusion, early initiated decontamination with the

  6. Transdermal drug delivery of labetalol hydrochloride: Feasibility and effect of penetration enhancers

    Directory of Open Access Journals (Sweden)

    Saqib Zafar

    2010-01-01

    Full Text Available Objectives : The objective of this study is to investigate the feasibility of transdermal drug delivery of Labetalol Hydrochloride (LHCl and to study the effect of different penetration enhancers on the skin permeability of LHCl. Methods : The permeability experiments were conducted using a horizontal glass diffusion cell with a diffusional area of 2.37 cm-2 on albino rat skin. The effect of various penetration enhancers namely turpentine oil, dimethyl formamide (DMF, menthol, dimethyl sulfoxide, pine oil, and 2-pyrollidone, and the effect of the concentration of drug and enhancer in the donor phase on the skin permeability of LHCl was studied. Results : The apparent partition coefficient of the drug was found to be 6.95, suggesting it to be a lipophilic drug. The preliminary skin permeation studies revealed that the permeation of LHCL through albino rat skin was moderate (Kp = 6.490 Χ 10 -2 cm hr -1 from isotonic phosphate buffer of pH 7.4. An appreciable increase in the LHCl permeability coefficient was observed on using a co-solvent (ethanol 95% with the penetration enhancers in the donor phase. DMSO (10% v/v was found to be the most effective enhancer for Labetalol hydrochloride (Enhancement Factor = 1.165. An increase in the concentration of drug and enhancer in the donor cell accentuated the permeability coefficient of LHCl. Conclusions : It was concluded that LHCl could be delivered via the dermal route with the use of 10% DMSO as the penetration enhancer.

  7. The Effect and Mechanism of Transdermal Penetration Enhancement of Fu's Cupping Therapy: New Physical Penetration Technology for Transdermal Administration with Traditional Chinese Medicine (TCM) Characteristics.

    Science.gov (United States)

    Xie, Wei-Jie; Zhang, Yong-Ping; Xu, Jian; Sun, Xiao-Bo; Yang, Fang-Fang

    2017-03-27

    In this paper, a new type of physical penetration technology for transdermal administration with traditional Chinese medicine (TCM) characteristics is presented. Fu's cupping therapy (FCT), was established and studied using in vitro and in vivo experiments and the penetration effect and mechanism of FCT physical penetration technology was preliminarily discussed. With 1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-ylacetic acid (indomethacin, IM) as a model drug, the establishment of high, medium, and low references was completed for the chemical permeation system via in vitro transdermal tests. Furthermore, using chemical penetration enhancers (CPEs) and iontophoresis as references, the percutaneous penetration effect of FCT for IM patches was evaluated using seven species of in vitro diffusion kinetics models and in vitro drug distribution; the IM quantitative analysis method in vivo was established using ultra-performance liquid chromatography-tandem mass spectrometry technology (UPLC-MS/MS), and pharmacokinetic parameters: area under the zero and first moment curves from 0 to last time t (AUC0-t, AUMC0-t), area under the zero and first moment curves from 0 to infinity (AUC0-∞, AUMC0-∞), maximum plasma concentration (Cmax) and mean residence time (MRT), were used as indicators to evaluate the percutaneous penetration effect of FCT in vivo. Additionally, we used the 3(K) factorial design to study the joint synergistic penetration effect on FCT and chemical penetration enhancers. Through scanning electron microscopy (SEM) and transmission electron microscope (TEM) imaging, micro- and ultrastructural changes on the surface of the stratum corneum (SC) were observed to explore the FCT penetration mechanism. In vitro and in vivo skin permeation experiments revealed that both the total cumulative percutaneous amount and in vivo percutaneous absorption amount of IM using FCT were greater than the amount using CPEs and iontophoresis. Firstly, compared with the

  8. In Vitro and In Vivo Measurement of Percutaneous Penetration of Low Molecular Weight Toxins of Military Interest

    Science.gov (United States)

    1989-01-19

    the metabolism cage and prevented radioactive exfoliated skin from falling into the collection device for urine and feces. The pigs were then housed...had penetrated into the skin. Part of the dose within the skin is in the stratum corneum and would probably be exfoliated if it was a i situation...hairless mice. 57 REFERENCES 1. Baden, D.G.(1983) Marine food-borne dinoflagellate toxins. International Review of Cytology 82,99. 2. Ellis, S. (1985

  9. The Penetration of Shaped Charges

    Institute of Scientific and Technical Information of China (English)

    Wu Mingde

    1996-01-01

    @@ In order to get the best perforating effect, many facts have to be considered. Perforating job is often design by computer. A perforating engineer has to decide the perforating technology and procedure, the gun and charge system, the shot density and phasing, the penetration and hole size, etc.

  10. Simulation of laser penetration efficiency

    Science.gov (United States)

    Semak, V. V.; Miller, T. F.

    2013-09-01

    The results of numerical simulation of laser beam interaction with a hypothetical metallic material with properties similar to a steel alloy are reported. The numerical simulation was performed using a physical model that includes detailed consideration of surface evaporation, evaporative cooling of the surface and evaporation recoil induced melt ejection. The laser beam ‘penetration’ is considered in terms of melting through the sample or drilling through the sample due to both evaporation and recoil ejection of material. As a demonstration of the predictive capabilities of the model, the average velocity of penetration through a material with steel-like properties is numerically predicted for various laser interaction parameters such as, laser beam radius, laser pulse duration (including CW regime), laser pulse energy and pulse repetition. In particular, the average penetration velocities through a sample due to melting are compared for pulsed and CW lasers of the same power. For the sake of another demonstration of penetration simulation, the temporal dynamics of the position of melt front relative to the sample surface irradiated by a laser beam was computed for different laser pulse repetition rates and constant average laser power. An illustration of the penetration efficiency (W parameter) defined as the amount of energy per unit volume delivered into a target in order to achieve either melting of drilling through a target wall is shown in a wide range of laser pulse parameters covering regimes corresponding to domination of melting through and drilling through.

  11. FAA Fluorescent Penetrant Laboratory Inspections

    Energy Technology Data Exchange (ETDEWEB)

    WINDES,CONNOR L.; MOORE,DAVID G.

    2000-08-02

    The Federal Aviation Administration Airworthiness Assurance NDI Validation Center currently assesses the capability of various non-destructive inspection (NDI) methods used for analyzing aircraft components. The focus of one such exercise is to evaluate the sensitivity of fluorescent liquid penetrant inspection. A baseline procedure using the water-washable fluorescent penetrant method defines a foundation for comparing the brightness of low cycle fatigue cracks in titanium test panels. The analysis of deviations in the baseline procedure will determine an acceptable range of operation for the steps in the inspection process. The data also gives insight into the depth of each crack and which step(s) of the inspection process most affect penetrant sensitivities. A set of six low cycle fatigue cracks produced in 6.35-mm thick Ti-6Al-4V specimens was used to conduct the experiments to produce sensitivity data. The results will document the consistency of the crack readings and compare previous experiments to find the best parameters for water-washable penetrant.

  12. Stylet penetration activities by aphids

    NARCIS (Netherlands)

    Tjallingii, W.F.

    1985-01-01

    The composition of stylet penetration behaviour in aphids and its possible role in food-plant selection is the subject of these studies. Evidence is presented that the labium is devoid of external chemoreceptors (Chapter 1). In addition to other morphological data (Wensler & Filshie, 1969; Wensler,

  13. Penetration Physics of Armor Glass

    Science.gov (United States)

    2009-11-30

    Penetration Response of Borosilicate Glass during Short Rod Impact”, Proc. 23rd Int. Symp. Ballistics, 2, 1251-1258, Graficas Couche, Madrid, Spain (2007...glass”, Proc. 23rd Int. Symp. Ballistics, 2, 1049-1056, Graficas Couche, Madrid, Spain (2007). 8D. R. Curran, “Comparison of Mesomechanical and

  14. Squamous cell skin cancer

    Science.gov (United States)

    ... that reflect light more, such as water, sand, concrete, and areas that are painted white. The higher ... - skin - squamous cell; Skin cancer - squamous cell; Nonmelanoma skin cancer - squamous ...

  15. Antioxidant cosmeto-textiles: skin assessment.

    Science.gov (United States)

    Alonso, Cristina; Martí, Meritxell; Martínez, Vanessa; Rubio, Laia; Parra, José L; Coderch, Luisa

    2013-05-01

    Resveratrol, a natural product, has been reported to have antioxidant activities such as the scavenging of free radicals. This compound could be used in the dermocosmetic field to protect the skin from oxidative stress. In this work, the percutaneous profile of resveratrol in ethanol solutions through pig skin was determinated by an in vitro methodology. The percutaneous absorption of resveratrol was measured and compared with trolox, an analogous of Vitamin E. Both antioxidants were found in all skin sections (stratum corneum, epidermis, and dermis). Besides, the free radical scavenging activity of resveratrol and trolox has been evaluated using DPPH method. The effective dose (ED₅₀) of compounds and DPPH radical inhibition in each skin layer were evaluated. Under the conditions used for these experiments, it can be deduced that resveratrol is more efficient than trolox as an antioxidant, also in the inner skin layers. The cosmeto-textiles with an active substance incorporated into their structure are increasingly used in the cosmetics and pharmaceutical industries. The action of several cosmeto-textiles on the skin was assessed by in vitro and in vivo methodologies. Samples of these cosmeto-textiles were prepared with resveratrol incorporated into cotton and polyamide fabrics. An in vitro percutaneous absorption was used to demonstrate the delivery of the resveratrol from the textile to the different skin layers (stratum corneum, epidermis, and dermis). Additionally, these cosmeto-textiles containing the antioxidant were applied onto the forearms of volunteers to evaluate the textiles' efficacy in skin penetration. The antioxidant's antiradical capacity was evaluated using the DPPH method. Results showed that resveratrol could be detected in the dermis, epidermis, and stratum corneum (SC) by an in vitro percutaneous absorption method and was also detected in the outermost layers of the SC by an in vivo method (stripping). A smaller amount of resveratrol was

  16. Percutaneous penetration enhancement effect of essential oil of mint (Mentha haplocalyx Briq. on Chinese herbal components with different lipophilicity

    Directory of Open Access Journals (Sweden)

    Jingyan Wang

    2014-10-01

    Conclusions: Mint oil at proper concentration could effectively facilitate percutaneous penetration of both lipophilic and hydrophilic drugs, and exhibit higher efficiency for moderate hydrophilic drugs. Mechanisms of penetration enhancement by mint oil could be explained with saturation solubility, SC/vehicle partition coefficient and the secondary structure change of SC.

  17. Topically applied ceramide accumulates in skin glyphs

    Science.gov (United States)

    Zhang, Qihong; Flach, Carol R; Mendelsohn, Richard; Mao, Guangru; Pappas, Apostolos; Mack, M Catherine; Walters, Russel M; Southall, Michael D

    2015-01-01

    Ceramides (CERs), structural components of the stratum corneum (SC), impart essential barrier properties to this thin outer layer of the epidermis. Variations in CER species within this layer have been linked to several skin diseases. A recent proliferation of CER-containing topical skin-care products warrants the elucidation of CER penetration profiles in both healthy and diseased skin. In the current study, the spatial distributions of CER concentration profiles, following topical application of two species of CER, were tracked using infrared imaging. Suspensions of single-chain perdeuterated sphingosine and phytosphingosine CER in oleic acid were applied, in separate experiments, to the surface of healthy intact ex vivo human skin using Franz diffusion cells. Following either a 24- or 48-hour incubation period at 34°C, infrared images were acquired from microtomed skin sections. Both CER species accumulated in glyph regions of the skin and penetrated into the SC, to a limited extent, only in these regions. The concentration profiles observed herein were independent of the CER species and incubation time utilized in the study. As a result, a very heterogeneous, sparse, spatial distribution of CERs in the SC was revealed. In contrast, oleic acid was found to be fairly homogeneously distributed throughout the SC and viable epidermis, albeit at lower concentrations in the latter. A more uniform, lateral distribution of CERs in the SC would likely be important for barrier efficacy or enhancement. PMID:26170709

  18. Intelligent instrument to facilitate decision making in the evaluation of soil resistance to root penetration Instrumentação inteligente para auxilio à tomada de decisão na avaliação da resistência do solo à penetração de raízes

    Directory of Open Access Journals (Sweden)

    Ladislau Marcelino Rabello

    2009-10-01

    Full Text Available This contribution introduces an instrument for decision-making in agricultural processes based on the measurements and mapping of soil resistance to root penetration. Its development was based on a new and advanced instrumentation tool, enabling in almost real-time to acquire the necessary information for spatial variability analysis of plant root penetration resistance in soils, due to natural or artificial soil compaction processes, i.e., not only for an area of soil but also for a soil profile. The system allows soil resistance assays for both laboratory and agricultural fields. Moreover, the development focused on an intelligent instrumentation concept, as well as a microprobe (30º for the spire angle, 1,6 mm for the base diameter, and 30 mm of total length, with a strain-gage transducer sensor. Results have shown that measurements of soil resistance to plant root penetration can be performed up to the limit of (483.47 ± 0.69 N, with a resolution of 15.4 N. Additionally, the versatility of the system is verified for soil resistance data collection and its interpretation to root plant penetration, since they can be presented in table formats, one-dimensional graphs, two-dimensional and three-dimensional maps. Therefore, this system enables users to obtain a quick interpretation of the soil aggregation state in agricultural areas.Neste trabalho é apresentado um instrumento para auxilio à tomada de decisão em processos que envolvem avaliações da resistência do solo à penetração de raízes. Seu desenvolvimento fundamenta-se na concepção de uma nova ferramenta instrumental avançada, que viabiliza em tempo quase real informações para análise da variabilidade espacial da resistência do solo à penetração de raízes, tanto para área como para perfil, devido aos processos de compactação natural ou artificial do solo. Ensaios para a medida da resistência do solo à penetração de raízes podem ser realizados tanto em ambiente

  19. Skin-light interaction of three main chromofores in skin affected by Port Wine Stain

    Science.gov (United States)

    Mújica Ascencio, S.; Velázquez González, J. S.; Álvarez Chávez, J. A.

    2013-11-01

    In this paper, simulation and mathematical analysis of the absorption, dispersion and dynamics of laser light generated at 690nm and its interaction with skin affected by the Port Wine Stain is presented. The absorption coefficient and penetration depth of water, hemoglobin and oxy-hemoglobin, as key chromophores are calculated. A suitable wavelength for possible treatment on Port Wine Stain located in the skin layers such as Dermis and Hypodermis is determined. The presentation will include a full fiber laser design description, detailed skin affectation explanation and preliminary results.

  20. Multiphoton STED and FRET in human skin: Resolving the skin barrier

    DEFF Research Database (Denmark)

    Antonescu, Irina; Dreier, Jes; Brewer, Jonathan R.

    Understanding the penetration properties of substances across biological bar- riers and membranes is vital for many areas of research. In the case of human skin, the barrier is primarily found in the stratum corneum and consists of protein-enriched cells surrounded by a lipid membrane -enriched...... excited STED and Forster Resonance Energy Transfer (FRET) microscopy to probe the structure of human skin. Super resolution optical microscopy enables resolving structures in the skin below to 60 nm allowing visualization of the stratum corneum intercellular lipid matrix and individual proteins...

  1. Defense against dermal exposures is only skin deep

    DEFF Research Database (Denmark)

    Nielsen, Jesper Bo; Nielsen, Flemming; Sørensen, Jens Ahm

    2007-01-01

    The OECD guideline for studies on percutaneous penetration to be used in hazard and risk evaluations prescribes experimental conditions with optimal barrier integrity of the skin, which in many occupational settings probably is not true. Thus, workers may have compromised skin due to chemical...... or mechanical damage, due to different medical conditions (eczema, dermatitis, skin irritation) or related to occupational scenarios involving prolonged wet work. The present study used the OECD guideline procedures to study the in vitro percutaneous penetration through human skin of a number of model...... substances (glyphosat, caffeine, benzoic acid, malathion) covering a range of solubilities. Further, we studied the extent to which a slightly damaged skin would change the rate, the amount absorbed during dermal exposure and the distribution of chemical deposition between epidermis and dermis. The present...

  2. Control of penetration zone GMAW

    Directory of Open Access Journals (Sweden)

    Віталій Петрович Iванов

    2016-11-01

    Full Text Available Thermal properties of the base metal, shielding medium and the nature of the electrode metal transfer to a great extent determine the penetration area formation in gas-arc welding. It is not always possible to take into account the influence of these factors on penetration front forming within the existing models. The aim of the work was to research the penetration area forming in gas-arc welding. The research of the penetration area forming in gas-arc welding of CrNi austenitic steels was made. The parameters of the regime as well as the kind of the gaseous medium influence on the formation of the penetration zone were studied. The article shows a linear proportional relationship between the electrode feed rate and the size of the base metal plate. The penetration area formation mode for welding in argon and carbon dioxide have been worked out. Diameter, feed rate and the speed of the electrode movement have been chosen as the main input parameters. Multiple regression analysis method was used to make up the modes. The relations of the third order that make it possible to take into account the electrode metal transfer and thermal properties change of the materials to be welded were used. These relationships show quite good agreement with the experimental measurements in the calculation of the fusion zone shape with consumable electrode in argon and carbon dioxide. It was determined that the shape of the melting front curve can be shown as a generalized function in which the front motion parameters depend on feed rate and the diameter of the electrode. Penetration zone growth time is determined by the welding speed and is calculated as a discrete function of the distance from the electrode with the spacing along the movement coordinate. The influence of the mode parameters on the formation of the fusion zone has been investigated and the ways to manage and stabilize the weld pool formation have been identified. The modes can be used to develop

  3. Akon - A Penetrator for Europa

    Science.gov (United States)

    Jones, Geraint

    2016-04-01

    Jupiter's moon Europa is one of the most intriguing objects in our Solar System. This 2000km-wide body has a geologically young solid water ice crust that is believed to cover a global ocean of liquid water. The presence of this ocean, together with a source of heating through tidal forces, make Europa a conceivable location for extraterrestrial life. The science case for exploring all aspects of this icy world is compelling. NASA has selected the Europa Mission (formerly Europa Clipper) to study Europa in detail in the 2020s through multiple flybys, and ESA's JUICE mission will perform two flybys of the body in the 2030s. The US agency has extended to the European Space Agency an invitation to provide a contribution to their mission. European scientists interested in Europa science and exploration are currently organizing themselves, in the framework of a coordinated Europa M5 Inititative to study concurrently the main options for this ESA contribution, from a simple addition of individual instruments to the NASA spacecraft, to a lander to investigate Europa's surface in situ. A high speed lander - a penetrator - is by far the most promising technology to achieve this latter option within the anticipated mass constraints, and studies of such a hard lander, many funded by ESA, are now at an advanced level. An international team to formally propose an Europa penetrator to ESA in response to the anticipated ESA M5 call is growing. The working title of this proposal is Akon (Άκων), named after the highly accurate javelin gifted to Europa by Zeus in ancient Greek mythology. We present plans for the Akon penetrator, which would impact Europa's surface at several hundred metres per second, and travel up to several metres into the moon's subsurface. To achieve this, the penetrator would be delivered to the surface by a dedicated descent module, to be destroyed on impact following release of the penetrator above the surface. It is planned that the instruments to be

  4. Filaggrin and Skin Barrier Function.

    Science.gov (United States)

    Kezic, Sanja; Jakasa, Ivone

    2016-01-01

    The skin barrier function is greatly dependent on the structure and composition of the uppermost layer of the epidermis, the stratum corneum (SC), which is made up of flattened anucleated cells surrounded by highly organized and continuous lipid matrix. The interior of the corneocytes consists mainly of keratin filaments aggregated by filaggrin (FLG) protein. Next, together with several other proteins, FLG is cross-linked into a mechanically robust cornified cell envelope providing a scaffold for the extracellular lipid matrix. In addition to its role for the SC structural and mechanical integrity, FLG degradation products account in part for the water-holding capacity and maintenance of acidic pH of the SC, both crucial for the epidermal barrier homoeostasis by regulating activity of multiple enzymes that control desquamation, lipid synthesis and inflammation. The major determinant of FLG expression in the skin are loss-of-function mutations in FLG, the strongest genetic risk factor for atopic dermatitis (AD), an inflammatory skin disease characterized by a reduced skin barrier function. The prevalence of FLG mutations varies greatly among different populations and ranges from about 10% in Northern Europeans to less than 1% in the African populations. An impaired skin barrier facilitates absorption of potentially hazardous chemicals, which might cause adverse effects in the skin, such as contact dermatitis, or systemic toxicity after their passage into blood. In another direction, a leaky epidermal barrier will lead to enhanced loss of water from the skin. A recent study has shown that even subtle increase in epidermal water loss in newborns increases the risk for AD. Although there are multiple modes of action by which FLG might affect skin barrier it is still unclear whether and how FLG deficiency leads to the reduced skin barrier function. This chapter summarizes the current knowledge in this field obtained from clinical studies, and animal and in vitro models

  5. Optimizing penetration depth, contrast, and resolution in 3D dermatologic OCT

    Science.gov (United States)

    Aneesh, Alex; Považay, Boris; Hofer, Bernd; Zhang, Edward Z.; Kendall, Catherine; Laufer, Jan; Popov, Sergei; Glittenberg, Carl; Binder, Susanne; Stone, Nicholas; Beard, Paul C.; Drexler, Wolfgang

    2010-02-01

    High speed, three-dimensional optical coherence tomography (3D OCT) at 800nm, 1060nm and 1300nm with approximately 4μm, 7μm and 6μm axial and less than 15μm transverse resolution is demonstrated to investigate the optimum wavelength region for in vivo human skin imaging in terms of contrast, dynamic range and penetration depth. 3D OCT at 1300nm provides deeper penetration, while images obtained at 800nm were better in terms of contrast and speckle noise. 1060nm region was a compromise between 800nm and 1300nm in terms of penetration depth and image contrast. Optimizing sensitivity, penetration and contrast enabled unprecedented visualization of micro-structural morphology underneath the glabrous skin, hairy skin and in scar tissue. Higher contrast obtained at 800 nm appears to be critical in the in vitro tumor study. A multimodal approach combining OCT and PA helped to obtain morphological as well as vascular information from deeper regions of skin.

  6. Skin Cancer Treatment

    Science.gov (United States)

    ... of Skin Cancer Skin Cancer Screening Research Skin Cancer Treatment (PDQ®)–Patient Version General Information About Skin Cancer ... clinical trials before, during, or after starting their cancer treatment. Some clinical trials only include patients who have ...

  7. Skin Pigmentation Disorders

    Science.gov (United States)

    Pigmentation means coloring. Skin pigmentation disorders affect the color of your skin. Your skin gets its color from a pigment called melanin. Special cells in the skin make melanin. When these cells become damaged or ...

  8. Skin Cancer Foundation

    Science.gov (United States)

    ... Host a Fundraising Event | About Us | Store The Skin Cancer Foundation The Skin Cancer Foundation is the only ... Handbook A "Sunscreen Gene"? Skin Cancer Facts & Statistics Skin Cancer Treatment Glossary Information on medications and procedures The ...

  9. Assessing high wind energy penetration

    DEFF Research Database (Denmark)

    Tande, J.O.

    1995-01-01

    In order to convincingly promote installing wind power capacity as a substantial part of the energy supply system, a set of careful analyses must be undertaken. This paper applies a case study concentrated on assessing the cost/benefit of high wind energy penetration. The case study considers...... expanding the grid connected wind power capacity in Praia, the capital of Cape Verde. The currently installed 1 MW of wind power is estimated to supply close to 10% of the electric energy consumption in 1996. Increasing the wind energy penetration to a higher level is considered viable as the project...... with the existing wind power, supply over 30% of the electric consumption in 1996. Applying the recommended practices for estimating the cost of wind energy, the life-cycle cost of this 2.4 MW investment is estimated at a 7% discount rate and a 20 year lifetime to 0.26 DKK/kW h....

  10. Weld penetration and defect control

    Energy Technology Data Exchange (ETDEWEB)

    Chin, B.A.

    1992-05-15

    Highly engineered designs increasingly require the use of improved materials and sophisticated manufacturing techniques. To obtain optimal performance from these engineered products, improved weld properties and joint reliability are a necessarily. This requirement for improved weld performance and reliability has led to the development of high-performance welding systems in which pre-programmed parameters are specified before any welding takes place. These automated systems however lack the ability to compensate for perturbations which arise during the welding process. Hence the need for systems which monitor and control the in-process status of the welding process. This report discusses work carried out on weld penetration indicators and the feasibility of using these indicators for on-line penetration control.

  11. IPMN penetration of the stomach.

    Science.gov (United States)

    Nakano, Masakazu; Tominaga, Keiichi; Watanabe, Hidetaka; Kanke, Kazunari; Tamano, Masaya; Hiraishi, Hideyuki

    2010-01-01

    An 83-year old Japanese man was transferred to our hospital due to a 1-week history of melena and signs of disordered awareness. Esophagogastroduodenoscopy showed a villous tumor associated with massive white mucous discharge in the posterior wall of the gastric corpus, where pathologically identified mucin-producing epithelium with nuclear atypia had developed into a papillary form. An abdominal enhanced computed tomography scan demonstrated communication between the dilated main pancreatic duct and the gastric lumen. Based on these findings, we reached a diagnosis of gastric penetration by an intraductal papillary mucinous neoplasm (IPMN) of the main pancreatic duct. IPMN is partly characterized by expansive mucinous growth that may result in penetration into adjacent organs.

  12. Learning facilitating leadership

    DEFF Research Database (Denmark)

    Rasmussen, Lauge Baungaard; Hansen, Mette Sanne

    2016-01-01

    in teaching facilitation and the literature. These types of skills are most effectively acquired by combining conceptual lectures, classroom exercises and the facilitation of groups in a real-life context. The paper also reflects certain ‘shadow sides’ related to facilitation observed by the students...

  13. Skin Bleaching

    OpenAIRE

    Ahmed, Samira M.

    2015-01-01

    In this project, I aim to investigate the reasoning behind the practice of skin bleaching by analyzing the documentary ”Dark Girls”, to gain a better understanding of race and colorism issues. Also this project tries to see if there is a connection with history and if this has been a part of making the european beauty ideal determine the choices black’s make in regards to beauty.

  14. Penetration Testing in Wireless Networks

    OpenAIRE

    Lamichhane, Shree

    2017-01-01

    This thesis illustrates the security measures and mechanisms behind the encryption and decryption of data while transmitting data in a wireless network. Furthermore, this thesis describes and demonstrates several security threats in a wireless network that are widely experienced. It also explains shortly the evolution of the widely implemented IEEE 802.11 standard and its amendments. Kali Linux tools were used to perform a penetration test in a WPA secured test network. In-formation on th...

  15. Transconjunctival penetration of mitomycin C

    OpenAIRE

    Velpandian T; Sihota Ramanjit; Sinha Ankur; Gupta Viney

    2008-01-01

    Aims: The study was performed to estimate transconjunctival penetration of mitomycin C (MMC) to Tenon′s tissue following application over the intact conjunctiva before routine trabeculectomy. Settings and Design: Institution-based case series. Materials and Methods: In 41 eyes of 41 patients, MMC (0.4 mg/ml for 3 min) was applied over the intact conjunctiva before beginning trabeculectomy. Tenon′s capsule directly beneath the site of application was excised during trabecule...

  16. Cardiac Penetrating Injuries and Pseudoaneurysm

    Institute of Scientific and Technical Information of China (English)

    CHEN Shifeng

    2002-01-01

    Objective To discuss the early diagnosis and treatment of cardiac penetrating injuries and pseudoaneurysm. Methods 18 cases of cardiac penetrating injuries, in which 2 cases were complicated with pseudoaneurysm, were diagnosed by emergency operation and color Doppler echocardiography between May 1973 and Dec. 2001 in our hospital. The basis for emergency operation is the injured path locating in cardiac dangerous zone, severe shock or pericardial tamponade. ResultsAmong 18 cases of this study, 17 cases underwent emergency operation. During the operation, 11 cases were found injured in right ventricle, 2 cases were found injured in right atrium, 1 case was found injured in pulmonary artery,4 cases were found injured in left ventricle, 2 cases were found complicated with pseudoaneurysm. 17cases underwent cardiac repair including 1 case of rupture of aneurysm. 1 case underwent elective aneurysm resection. In whole group, 15 cases survived(83.33% ), 3 cases died( 16.67%). The cause of death is mainly hemorrhagic shock. Conclusion Highly suspicious cardiac penetrating injuries or hemopericaridium should undergo direct operative exploration. Pseudoaneurysm should be resected early,which can prevent severe complications.

  17. Locating a buried earth penetrator

    Energy Technology Data Exchange (ETDEWEB)

    Caffey, T.W.H.

    1977-11-01

    The purpose of this work was to assist the recovery of a buried earth penetrator by locating the vertical projection of the penetator upon the surface within a horizontal radius error of one meter. The penetrator will carry a small coil which is driven by an alternating current to form a magnetic dipole. Five measurements of the magnetic field vector upon the surface of the earth are shown to be sufficient for determining not only the xyz-coordinates of the dipole, but also the orientation of the dipole axis. The theory, computation process, and field tests are comprehensively described. Results of 26 field tests with the dipole at 9 different combinations of location and orientation are given. Average radial and vertical location errors are 0.27 m and -0.05 m, respectively, while the mean errors in the tilt and orientation angles of the dipole axis are 3 degrees and 8 degrees, respectively. The results are applied to the design of a locating system for a Pershing II penetrator which contains a recessed, rear-mounted coil.

  18. Correlation Between Cone Penetration Rate And Measured Cone Penetration Parameters In Silty Soils

    DEFF Research Database (Denmark)

    Poulsen, Rikke; Nielsen, Benjaminn Nordahl; Ibsen, Lars Bo

    2013-01-01

    penetration tests with varying penetration rates conducted at a test site where the subsoil primary consists of sandy silt. It is shown how a reduced penetration rate influences the cone penetration measurements e.g. the cone resistance, pore pressure, and sleeve friction.......This paper shows, how a change in cone penetration rate affects the cone penetration measurements, hence the cone resistance, pore pressure, and sleeve friction in silty soil. The standard rate of penetration is 20 mm/s, and it is generally accepted that undrained penetration occurs in clay while...... drained penetration occurs in sand. When lowering the penetration rate, the soil pore water starts to dissipate and a change in the drainage condition is seen. In intermediate soils such as silty soils, the standard cone penetration rate may result in a drainage condition that could be undrained...

  19. Cutaneous skin tag

    Science.gov (United States)

    Skin tag; Acrochordon; Fibroepithelial polyp ... have diabetes. They are thought to occur from skin rubbing against skin. ... The tag sticks out of the skin and may have a short, narrow stalk connecting it to the surface of the skin. Some skin tags are as long as ...

  20. Ethical Dilemmas and Dimensions in Penetration Testing

    OpenAIRE

    Faily, Sharmal; McAlaney, John; Iacob, C

    2015-01-01

    Penetration testers are required to attack systems to evaluate their security, but without engaging in unethical behaviour while doing so. Despite work on hacker values and studies into security practice, there is little literature devoted to the ethical pressures associated with penetration testing. This paper presents several ethical dilemmas and dimensions associated with penetration testing;\\ud these shed light on the ethical positions taken by Penetration testers, and help identify poten...

  1. The production process for water penetrated brick

    Institute of Scientific and Technical Information of China (English)

    SunGuofeng

    2005-01-01

    Waste penetrated brick, which is a green building material with good water penetration, high strength, lower firing temperature, lower production cost, good appearance and good structure, can holding ground water lever. This article analysis the production process and related factor for water penetrated brick:proper particle size distribution, proper shaping method, proper press and proper firing can ensure to produce good quality water penetrated brick.

  2. Penetration Testing: A Roadmap to Network Security

    OpenAIRE

    2009-01-01

    Network penetration testing identifies the exploits and vulnerabilities those exist within computer network infrastructure and help to confirm the security measures. The objective of this paper is to explain methodology and methods behind penetration testing and illustrate remedies over it, which will provide substantial value for network security Penetration testing should model real world attacks as closely as possible. An authorized and scheduled penetration testing will probably detected ...

  3. Network Penetration Testing and Research

    Science.gov (United States)

    Murphy, Brandon F.

    2013-01-01

    This paper will focus the on research and testing done on penetrating a network for security purposes. This research will provide the IT security office new methods of attacks across and against a company's network as well as introduce them to new platforms and software that can be used to better assist with protecting against such attacks. Throughout this paper testing and research has been done on two different Linux based operating systems, for attacking and compromising a Windows based host computer. Backtrack 5 and BlackBuntu (Linux based penetration testing operating systems) are two different "attacker'' computers that will attempt to plant viruses and or NASA USRP - Internship Final Report exploits on a host Windows 7 operating system, as well as try to retrieve information from the host. On each Linux OS (Backtrack 5 and BlackBuntu) there is penetration testing software which provides the necessary tools to create exploits that can compromise a windows system as well as other operating systems. This paper will focus on two main methods of deploying exploits 1 onto a host computer in order to retrieve information from a compromised system. One method of deployment for an exploit that was tested is known as a "social engineering" exploit. This type of method requires interaction from unsuspecting user. With this user interaction, a deployed exploit may allow a malicious user to gain access to the unsuspecting user's computer as well as the network that such computer is connected to. Due to more advance security setting and antivirus protection and detection, this method is easily identified and defended against. The second method of exploit deployment is the method mainly focused upon within this paper. This method required extensive research on the best way to compromise a security enabled protected network. Once a network has been compromised, then any and all devices connected to such network has the potential to be compromised as well. With a compromised

  4. Influence of metabolism in skin on dosimetry after topical exposure

    Energy Technology Data Exchange (ETDEWEB)

    Bronaugh, R.L.; Collier, S.W.; Macpherson, S.E.; Kraeling, M.E.K. [Food and Drug Administration, Washington, DC (United States)

    1994-12-01

    Metabolism of chemicals occurs in skin and therefore should be taken into account when one determines topical exposure dose. Skin metabolism is difficult to measure in vivo because biological specimens may also contain metabolites from other tissues. Metabolism in skin during percutaneous absorption can be studied with viable skin in flow-through diffusion cells. Several compounds metabolized by microsomal enzymes in skin (benzo[a]pyrene and 7-ethoxycoumarin) penetrated human and hairless guinea pig skin predominantly unmetabolized. However, compounds containing a primary amino group (p-aminobenzoic acid, benzocaine, and azo color reduction products) were substrates for acetyltransferase activity in skin and were substantially metabolized during absorption. A physiologically based pharmacokinetic model has been developed with an input equation, allowing modeling after topical exposure. 14 refs., 3 figs., 4 tabs.

  5. Influence of metabolism in skin on dosimetry after topical exposure.

    Science.gov (United States)

    Bronaugh, R L; Collier, S W; Macpherson, S E; Kraeling, M E

    1994-12-01

    Metabolism of chemicals occurs in skin and therefore should be taken into account when one determines topical exposure dose. Skin metabolism is difficult to measure in vivo because biological specimens may also contain metabolites from other tissues. Metabolism in skin during percutaneous absorption can be studied with viable skin in flow-through diffusion cells. Several compounds metabolized by microsomal enzymes in skin (benzo[a]pyrene and 7-ethoxycoumarin) penetrated human and hairless guinea pig skin predominantly unmetabolized. However, compounds containing a primary amino group (p-aminobenzoic acid, benzocaine, and azo color reduction products) were substrates for acetyltransferase activity in skin and were substantially metabolized during absorption. A physiologically based pharmacokinetic model has been developed with an input equation, allowing modeling after topical exposure. Plasma concentrations in the hairless guinea pig were accurately predicted for the model compound, benzoic acid, from in vitro absorption, metabolism, and other pharmacokinetic parameters.

  6. 7 CFR 2902.14 - Penetrating lubricants.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Penetrating lubricants. 2902.14 Section 2902.14... Items § 2902.14 Penetrating lubricants. (a) Definition. Products formulated to provide light lubrication..., will give a procurement preference for qualifying biobased penetrating lubricants. By that...

  7. Kali Linux wireless penetration testing essentials

    CERN Document Server

    Alamanni, Marco

    2015-01-01

    This book is targeted at information security professionals, penetration testers and network/system administrators who want to get started with wireless penetration testing. No prior experience with Kali Linux and wireless penetration testing is required, but familiarity with Linux and basic networking concepts is recommended.

  8. In vitro evaluation of cutaneous penetration of acyclovir from semisolid commercial formulations and relation with its effective antiviral concentration

    Directory of Open Access Journals (Sweden)

    Rafaela Martins Sponchiado

    Full Text Available ABSTRACT The evaluation of drug permeation/penetration of semisolid formulations into animal skin can be useful to supplement the pharmaceutical equivalence. This paper describes the in vitro assessment of acyclovir (ACV into porcine skin from commercial formulations with etermination of drug concentration in different layers of cutaneous tissue to correlate with effective antiviral concentration in order to improve the equivalence decision. Studies were conducted using Franz cells and porcine skin. Selected pharmaceutical creams containing ACV had identical (reference and generic and different (similar excipients. A software program was employed for the simulation of antiviral effectiveness in the skin. Regarding ACV skin penetration, the first batch of the generic product showed a significant difference from reference and similar products, while in the second batch all products demonstrated equivalent drug penetration in the skin. Simulation studies suggest that formulations analysed exhibit a pharmacological effect even when in contact with Herpes simplex strains of high IC50 (inhibitory concentration required to reduce viral replication by 50%. According to results, it can be assumed that the in vitro cutaneous permeation/penetration study does not supply sensitivity information regarding small alterations of ACV semisolid formulations due to the variability inherent to the method, although it can be relevant to pharmaceutical equivalence studies in the development of semisolid products.

  9. A study on the quantitative evaluation of skin barrier function

    Science.gov (United States)

    Maruyama, Tomomi; Kabetani, Yasuhiro; Kido, Michiko; Yamada, Kenji; Oikaze, Hirotoshi; Takechi, Yohei; Furuta, Tomotaka; Ishii, Shoichi; Katayama, Haruna; Jeong, Hieyong; Ohno, Yuko

    2015-03-01

    We propose a quantitative evaluation method of skin barrier function using Optical Coherence Microscopy system (OCM system) with coherency of near-infrared light. There are a lot of skin problems such as itching, irritation and so on. It has been recognized skin problems are caused by impairment of skin barrier function, which prevents damage from various external stimuli and loss of water. To evaluate skin barrier function, it is a common strategy that they observe skin surface and ask patients about their skin condition. The methods are subjective judgements and they are influenced by difference of experience of persons. Furthermore, microscopy has been used to observe inner structure of the skin in detail, and in vitro measurements like microscopy requires tissue sampling. On the other hand, it is necessary to assess objectively skin barrier function by quantitative evaluation method. In addition, non-invasive and nondestructive measuring method and examination changes over time are needed. Therefore, in vivo measurements are crucial for evaluating skin barrier function. In this study, we evaluate changes of stratum corneum structure which is important for evaluating skin barrier function by comparing water-penetrated skin with normal skin using a system with coherency of near-infrared light. Proposed method can obtain in vivo 3D images of inner structure of body tissue, which is non-invasive and non-destructive measuring method. We formulate changes of skin ultrastructure after water penetration. Finally, we evaluate the limit of performance of the OCM system in this work in order to discuss how to improve the OCM system.

  10. Mass transport model through the skin by microencapsulation system.

    Science.gov (United States)

    Carreras, Núria; Alonso, Cristina; Martí, Meritxell; Lis, Manel J

    2015-01-01

    Skin drug delivery can be subdivided into topical and transdermal administration. Transdermal administration can take advantage of chemical and physical strategies that can improve skin permeability and allow drug penetration. In this study, the development of a skin penetration profile was carried out by an in vitro technique for a microencapsulated system of ibuprofen. Release experiments were performed using percutaneous absorption tests to determine the evolution of the principle present in each of the different skin compartments as a function of time. A general kinetic model for a microencapsulated structure as a mass transport system through the skin was applied: [Formula: see text] This model could predict the penetration profile of encapsulated substances through skin from biofunctional textiles as well as estimate the dosage profile of the active principle. The apparent diffusion coefficients found were 1.20 × 10(-7 )cm/s for the stratum corneum and higher for the rest of the skin 6.67 × 10(-6 )cm/s.

  11. The 2008 ICOH Workshop on Skin Notation

    DEFF Research Database (Denmark)

    Sartorelli, P; Ahlers, H W; Cherrie, J W

    2010-01-01

    BACKGROUND: On 29 March 2008 the International Commission on Occupational Health (ICOH) Scientific Committee on Occupational and Environmental Dermatoses organized a Skin Notation Workshop hosted by the 11th International Percutaneous Penetration Perspectives Conference (La Grande Motte, France......). Skin notation (S) was chosen as a topic for discussion because this is the only example of existing regulation in the field of dermal risk assessment. The issue was discussed in a previous workshop held in Siena, Italy in 2006 with the objective of focussing on the problems related to S, the different...

  12. FAA Fluorescent Penetrant Activities - An Update

    Energy Technology Data Exchange (ETDEWEB)

    Moore, D.G.

    1998-10-20

    The Federal Aviation Administration's Airworthiness Assurance NDI Validation Center (AANC) is currently characterizing low cycle fatigue specimens that will support the needs of penetrant manufacturers, commercial airline industry and the Federal Aviation Administration. The main focus of this characterization is to maintain and enhance the evaluation of penetrant inspection materials and apply resources to support the aircraft community needs. This paper discusses efforts to-date to document the Wright Laboratory penetrant evaluation process and characterize penetrant brightness readings in the initial set of sample calibration panels using Type 1 penetrant.

  13. Web penetration testing with Kali Linux

    CERN Document Server

    Muniz, Joseph

    2013-01-01

    Web Penetration Testing with Kali Linux contains various penetration testing methods using BackTrack that will be used by the reader. It contains clear step-by-step instructions with lot of screenshots. It is written in an easy to understand language which will further simplify the understanding for the user.""Web Penetration Testing with Kali Linux"" is ideal for anyone who is interested in learning how to become a penetration tester. It will also help the users who are new to Kali Linux and want to learn the features and differences in Kali versus Backtrack, and seasoned penetration testers

  14. Economic Operation of Power Systems with Significant Wind Power Penetration

    DEFF Research Database (Denmark)

    Farashbashi-Astaneh, Seyed-Mostafa

    This dissertation addresses economic operation of power systems with high penetration of wind power. Several studies are presented to address the economic operation of power systems with high penetration of variable wind power. The main concern in such power systems is high variability...... level should be economic and can be a provided by different tools such as developing new reserve scheduling techniques, demand response, using storage units, facilitating the capacity of cross-border interconnections and so on. These subjects are addressed in this PhD dissertation. In the first study...... (and thus power system security is enhanced). The optimal charging scheme of Eclectic Vehicles (EVs) in a distribution feeder is then studied considering the proposed pricing scheme. A formulation is then proposed for optimal reserve scheduling considering the role of reserve provision scenarios from...

  15. Understanding engineered nanomaterial skin interactions and the modulatory effects of ultraviolet radiation skin exposure.

    Science.gov (United States)

    Jatana, Samreen; DeLouise, Lisa A

    2014-01-01

    The study of engineered nanomaterials for the development of technological applications, nanomedicine, and nano-enabled consumer products is an ever-expanding discipline as is the concern over the impact of nanotechnology on human environmental health and safety. In this review, we discuss the current state of understanding of nanomaterial skin interactions with a specific emphasis on the effects of ultraviolet radiation (UVR) skin exposure. Skin is the largest organ of the body and is typically exposed to UVR on a daily basis. This necessitates the need to understand how UVR skin exposure can influence nanomaterial skin penetration, alter nanomaterial systemic trafficking, toxicity, and skin immune function. We explore the unique dichotomy that UVR has on inducing both deleterious and therapeutic effects in skin. The subject matter covered in this review is broadly informative and will raise awareness of potential increased risks from nanomaterial skin exposure associated with specific occupational and life style choices. The UVR-induced immunosuppressive response in skin raises intriguing questions that motivate future research directions in the nanotoxicology and nanomedicine fields. © 2013 Wiley Periodicals, Inc.

  16. Penetration testing with Raspberry Pi

    CERN Document Server

    Muniz, Joseph

    2015-01-01

    If you are looking for a low budget, small form-factor remotely accessible hacking tool, then the concepts in this book are ideal for you. If you are a penetration tester who wants to save on travel costs by placing a low-cost node on a target network, you will save thousands by using the methods covered in this book. You do not have to be a skilled hacker or programmer to use this book. It will be beneficial to have some networking experience; however, it is not required to follow the concepts covered in this book.

  17. Penetration Testing: A Roadmap to Network Security

    CERN Document Server

    Naik, Nitin A; Khamitkar, Santosh D; Kalyankar, Namdeo V

    2009-01-01

    Network penetration testing identifies the exploits and vulnerabilities those exist within computer network infrastructure and help to confirm the security measures. The objective of this paper is to explain methodology and methods behind penetration testing and illustrate remedies over it, which will provide substantial value for network security Penetration testing should model real world attacks as closely as possible. An authorized and scheduled penetration testing will probably detected by IDS (Intrusion Detection System). Network penetration testing is done by either or manual automated tools. Penetration test can gather evidence of vulnerability in the network. Successful testing provides indisputable evidence of the problem as well as starting point for prioritizing remediation. Penetration testing focuses on high severity vulnerabilities and there are no false positive.

  18. Learning facilitating leadership

    DEFF Research Database (Denmark)

    Rasmussen, Lauge Baungaard; Hansen, Mette Sanne

    2016-01-01

    This paper explains how engineering students at a Danish university acquired the necessary skills to become emergent facilitators of organisational development. The implications of this approach are discussed and related to relevant viewpoints and findings in the literature. The methodology deplo....... By connecting the literature, the authors’ and engineering students’ reflections on facilitator skills, this paper adds value to existing academic and practical discussions on learning facilitating leadership....

  19. Visual explorer facilitator's guide

    CERN Document Server

    Palus, Charles J

    2010-01-01

    Grounded in research and practice, the Visual Explorer™ Facilitator's Guide provides a method for supporting collaborative, creative conversations about complex issues through the power of images. The guide is available as a component in the Visual Explorer Facilitator's Letter-sized Set, Visual Explorer Facilitator's Post card-sized Set, Visual Explorer Playing Card-sized Set, and is also available as a stand-alone title for purchase to assist multiple tool users in an organization.

  20. Ethosomes for enhanced skin delivery of griseofulvin.

    Science.gov (United States)

    Marto, Joana; Vitor, Catarina; Guerreiro, Ana; Severino, Cristiana; Eleutério, Carla; Ascenso, Andreia; Simões, Sandra

    2016-10-01

    Griseofulvin (GRF) is an important antifungal drug with low bioavailability and, for this reason, a topical formulation with a targeted action and minimal systemic effects, appears to be a preferable solution. GRF poor solubility has limited the development of topical formulations and their release to the market. The aim of this work was to prepare a new GRF formulation for topical application using lipid-based nanosystems; to study its permeation and penetration, cell viability and to evaluate its therapeutic action. Ethosomal systems composed of soy bean phosphatidylcholine, ethanol and water were prepared for incorporating GRF. After the characterization of the vesicles in terms of size, charge and penetrability, permeation through newborn pig using Franz diffusion cells was conducted. Cell viability at different concentrations of the chosen formulation was determined. At last, skin adapted agar diffusion test was performed to assess the therapeutic efficacy of the formulation. GRF vesicles had mean size of 130nm. Permeation and penetration assays revealed that GRF-loaded ethosomes have an adequate profile to be used in a topical formulation since drug retention in the stratum corneum was achieved. Cell viability tests proved this formulation presented no cytotoxicity to HaCaT cells for concentrations below 50μg/mL. The skin diffusion test evidenced the potential of developed formulation to target skin dermatophytes. The results obtained in this study contribute to a new perspective in topical treatment of fungal infections.

  1. Anyone Can Get Skin Cancer

    Science.gov (United States)

    ... of Skin Cancer Skin Cancer Screening Research Anyone Can Get Skin Cancer Order the free Anyone Can ... rarely, younger children can develop skin cancer. How can people with dark skin get skin cancer? Although ...

  2. The challenges of facilitation

    DEFF Research Database (Denmark)

    Agger, Annika

    and at the same time make closures in order to secure progress in the process? The analysis draws upon theoretical perspectives on deliberative democracy and facilitation. Whereas, the scholarly literature on deliberative democracy is rich in describing potential outcomes and criteria for deliberative processes...... hours transcriptions of three table deliberations; questionnaires of 91 participants, 2 focus group interviews with participants and facilitators....

  3. Training facilitators and supervisors

    DEFF Research Database (Denmark)

    Kjær, Louise Binow; O Connor, Maja; Krogh, Kristian;

    At the Master’s program in Medicine at Aarhus University, Denmark, we have developed a faculty development program for facilitators and supervisors in 4 progressing student modules in communication, cooperation, and leadership. 1) A course for module 1 and 3 facilitators inspired by the apprentic...

  4. Transmission of phototherapy through human skin: dosimetry adjustment for effects of skin color, body composition, wavelength, and light coupling to skin

    Science.gov (United States)

    Nussbaum, Ethne L.; Van Zuylen, Jeff

    2006-02-01

    Purpose: To examine factors that affect penetration of phototherapy. Methods: Age, sex, height, and weight were recorded; skin color, skinfold thickness, and light transmission through a skinfold were measured over biceps and triceps muscles, and at the anterior waistline. Light was generated using two 23-diode LED arrays at 840 nm and 660 nm with surface area of 7 cm2. Photon irradiation was measured using an Optical Power Meter consisting of a 1x1-cm2 light detector placed in the centre of the illuminated 7 cm2 spot. Transmission was measured using three skin-diode coupling conditions. Results: Penetration of LED irradiation increased when diodes were coupled to skin with pressure. Red light attenuated more rapidly than infrared light and the attenuation of red light increased as skin color darkened. Penetration of red and infrared light decreased as the amount of subcutaneous fat increased. There were gender effects on penetration of infrared light at normal and low BMI values. Conclusions: When using divergent light sources for phototherapy, radiant exposure should take into account individual physical characteristics, irradiation wavelength and diode configuration of the laser therapy system.

  5. Abnormally dark or light skin

    Science.gov (United States)

    Hyperpigmentation; Hypopigmentation; Skin - abnormally light or dark ... Normal skin contains cells called melanocytes. These cells produce melanin , the substance that gives skin its color. Skin with ...

  6. Measurement of diffusion coefficient of propylene glycol in skin tissue

    Science.gov (United States)

    Genin, Vadim D.; Bashkatov, Alexey N.; Genina, Elina A.; Tuchin, Valery V.

    2015-03-01

    Optical clearing of the rat skin under the action of propylene glycol was studied ex vivo. It was found that collimated transmittance of skin samples increased, whereas weight and thickness of the samples decreased during propylene glycol penetration in skin tissue. A mechanism of the optical clearing under the action of propylene glycol is discussed. Diffusion coefficient of propylene glycol in skin tissue ex vivo has been estimated as (1.35±0.95)×10-7 cm2/s with the taking into account of kinetics of both weight and thickness of skin samples. The presented results can be useful for enhancement of many methods of laser therapy and optical diagnostics of skin diseases and localization of subcutaneous neoplasms.

  7. Percutaneous Absorption and Metabolism of Ketoprofen Isopropyl Ester via Excised Nude Mouse‘s and Monkey’s Skin

    Institute of Scientific and Technical Information of China (English)

    ZHUQuan-gang; HUJin-hong

    2003-01-01

    Aim:To study percutaneous absorption and metabolism of ketoprofen isopropyl ester (KPE)via excised nude mouse's and monkey's skin.Methods:Excised skin was prepared by surgical excision and enzyme digestion.Sideby-side diffusion cells were used for in vitro permeation studies.The concentrations of KPE and its metabolite in samples were assayed by HPLC.Results:All KPE penetration through whole thickness skin and stripped skin was metabolized to ketoprofen(KP).the concentration of which in the reciiver solution increased linearly with time.As to the nude mouse skin.the steady-state flux of KP through whole thickness skin was 2.5 times that of KPE through the whloe thickness skin,but the KP and KPE remaining in the whole thickness skin after the finishing of KPE penetration was 22.2 times in compered with the KP remaining in the whole thickness skin after the finshing of KP penetration.The rate of formation of the steady state KP from KPE throught dermis was significantly lower than that of KPE through the whole thickness skin.In he monkey skin,the rate of formation of the steady-state KP from KPE through the whole thickness skin was 0.7 times that from KPE through stripped skin.The KP and KPE remaining in the whole thickness skin after the finishing of KPE penetration was 2.0 time that in the stripped skin after the finishing of KPE penetration.The rate of fornation of the steady-state KP from KPE through dermis was lower than that from KPE through the whole thickness skin and the stripped skin.the KP remaining in dermis after the finsihing of KPE penetration was also significantly lower than the KP remaining in the whole thickness skin and the stripped skin after the finishing of KPE penetration.Conclusion:KP esters are of benefit to imporove the local action of KP.and skin esterase metabolism mainly develops in the epidermis.

  8. Synergistic effect of chemical penetration enhancer and iontophoresis on transappendageal transport of oligodeoxynucleotides.

    Science.gov (United States)

    Liu, Keng-Chih; Green, Colin R; Alany, Raid G; Rupenthal, Ilva D

    2013-01-30

    Gap junction protein connexin43 (Cx43) specific antisense oligodeoxynucleotides (AsODN) have been shown to improve a number of inflammatory conditions and may therefore offer a novel strategy for persistent pain management. However, for such molecules to be clinically effective, delivery challenges owing to the molecules' high molecular weight, negative charge and hydrophilicity have to be overcome. In this study, the effect of various chemical penetration enhancers and cathodal iontophoresis on transdermal delivery was evaluated. Initial skin permeation studies revealed only a slight increase in the passive flux of the model anionic drug sodium fluorescein using limonene/ethanol. Applying cathodal iontophoresis, the amount of the model drug permeated through untreated skin was tripled, while a combination of chemical and physical penetration enhancement resulted in a fourfold increase in the fluorescein amount permeated. However, even the synergistic effect of limonene/ethanol and iontophoresis was insufficient to achieve complete permeation of Cy3-labeled Cx43 AsODN across the entire skin thickness. Instead, molecules were trapped in the epidermis or permeated deeply into the hair follicles. These results suggest that the synergistic effect of chemical and physical penetration enhancement increases intradermal delivery of oligonucleotides but is insufficient to deliver such large molecules across intact skin.

  9. Ethical hacking and penetration testing guide

    CERN Document Server

    Baloch, Rafay

    2014-01-01

    Requiring no prior hacking experience, Ethical Hacking and Penetration Testing Guide supplies a complete introduction to the steps required to complete a penetration test, or ethical hack, from beginning to end. You will learn how to properly utilize and interpret the results of modern-day hacking tools, which are required to complete a penetration test. The book covers a wide range of tools, including Backtrack Linux, Google reconnaissance, MetaGooFil, dig, Nmap, Nessus, Metasploit, Fast Track Autopwn, Netcat, and Hacker Defender rootkit. Supplying a simple and clean explanation of how to effectively utilize these tools, it details a four-step methodology for conducting an effective penetration test or hack.Providing an accessible introduction to penetration testing and hacking, the book supplies you with a fundamental understanding of offensive security. After completing the book you will be prepared to take on in-depth and advanced topics in hacking and penetration testing. The book walks you through each ...

  10. Cable Braid Electromagnetic Penetration Model.

    Energy Technology Data Exchange (ETDEWEB)

    Warne, Larry K. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Langston, William L. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Basilio, Lorena I. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Johnson, W. A. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States)

    2015-06-01

    The model for penetration of a wire braid is rigorously formulated. Integral formulas are developed from energy principles and reciprocity for both self and transfer immittances in terms of potentials for the fields. The detailed boundary value problem for the wire braid is also setup in a very efficient manner; the braid wires act as sources for the potentials in the form of a sequence of line multipoles with unknown coefficients that are determined by means of conditions arising from the wire surface boundary conditions. Approximations are introduced to relate the local properties of the braid wires to a simplified infinite periodic planar geometry. This is used in a simplified application of reciprocity to be able to treat nonuniform coaxial geometries including eccentric interior coaxial arrangements and an exterior ground plane.

  11. Respirator Testing Using Virus Aerosol: Comparison between Viability Penetration and Physical Penetration.

    Science.gov (United States)

    Zuo, Zhili; Kuehn, Thomas H; Pui, David Y H

    2015-07-01

    Viability, fluorescence (particle volume), photometric, viral RNA, and particle number penetration of MS2 bacteriophage through filter media used in three different models of respirators were compared to better understand the correlation between viability and physical penetration. Although viability and viral RNA penetration were better represented by particle volume penetration than particle number penetration, they were several-fold lower than photometric penetration, which was partially due to the difference in virus survival between upstream and downstream aerosol samples. Results suggest that the current NIOSH photometer-based test method can be used as a quick means to roughly differentiate respirators with different performance against virus aerosols.

  12. Bodily action penetrates affective perception

    Directory of Open Access Journals (Sweden)

    Carlo Fantoni

    2016-02-01

    Full Text Available Fantoni & Gerbino (2014 showed that subtle postural shifts associated with reaching can have a strong hedonic impact and affect how actors experience facial expressions of emotion. Using a novel Motor Action Mood Induction Procedure (MAMIP, they found consistent congruency effects in participants who performed a facial emotion identification task after a sequence of visually-guided reaches: a face perceived as neutral in a baseline condition appeared slightly happy after comfortable actions and slightly angry after uncomfortable actions. However, skeptics about the penetrability of perception (Zeimbekis & Raftopoulos, 2015 would consider such evidence insufficient to demonstrate that observer’s internal states induced by action comfort/discomfort affect perception in a top-down fashion. The action-modulated mood might have produced a back-end memory effect capable of affecting post-perceptual and decision processing, but not front-end perception. Here, we present evidence that performing a facial emotion detection (not identification task after MAMIP exhibits systematic mood-congruent sensitivity changes, rather than response bias changes attributable to cognitive set shifts; i.e., we show that observer’s internal states induced by bodily action can modulate affective perception. The detection threshold for happiness was lower after fifty comfortable than uncomfortable reaches; while the detection threshold for anger was lower after fifty uncomfortable than comfortable reaches. Action valence induced an overall sensitivity improvement in detecting subtle variations of congruent facial expressions (happiness after positive comfortable actions, anger after negative uncomfortable actions, in the absence of significant response bias shifts. Notably, both comfortable and uncomfortable reaches impact sensitivity in an approximately symmetric way relative to a baseline inaction condition. All of these constitute compelling evidence of a genuine top

  13. Skin color - patchy

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003224.htm Skin color - patchy To use the sharing features on this page, please enable JavaScript. Patchy skin color is areas where the skin color is irregular. ...

  14. Nanoparticle exposure in animals can be visualized in the skin and analysed via skin biopsy

    Science.gov (United States)

    Sykes, Edward A.; Dai, Qin; Tsoi, Kim M.; Hwang, David M.; Chan, Warren C. W.

    2014-05-01

    The increasing use of nanomaterials raises concerns about the long-term effects of chronic nanoparticle exposure on human health. However, nanoparticle exposure is difficult to evaluate non-invasively using current measurement techniques. Here we show that the skin is an important site of nanoparticle accumulation following systemic administration. Mice injected with high doses of gold nanoparticles have visibly blue skin while quantum dot-treated animals fluoresce under ultraviolet excitation. More importantly, elemental analysis of excised skin correlates with the injected dose and nanoparticle accumulation in the liver and spleen. We propose that skin analysis may be a simple strategy to quantify systemic nanoparticle exposure and predict nanoparticle fate in vivo. Our results suggest that in the future, dermal accumulation may also be exploited to trigger the release of ultraviolet and visible light-sensitive therapeutics that are currently impractical in vivo due to limits in optical penetration of tissues at these wavelengths.

  15. A Multiple Scattering Theory for Proton Penetration

    Institute of Scientific and Technical Information of China (English)

    YANG Dai-Lun; WU Zhang-Wen; JIANG Steve-Bin; LUO Zheng-Ming

    2004-01-01

    @@ We extend the electron small-angle multiple scattering theory to proton penetration. After introducing the concept of narrow energy spectra, the proton energy loss process is included in the proton deep penetration theory. It precisely describes the whole process of proton penetration. Compared to the Monte Carlo method,this method maintains the comparable precision and possesses much higher computational efficiency. Thus, it shows the real feasibility of applying this algorithm to proton clinical radiation therapy.

  16. In-place HEPA filter penetration test

    Energy Technology Data Exchange (ETDEWEB)

    Bergman, W.; Wilson, K.; Elliott, J. [Lawrence Livermore National Lab., CA (United States)] [and others

    1997-08-01

    We have demonstrated the feasibility of conducting penetration tests on high efficiency particulate air (HEPA) filters as installed in nuclear ventilation systems. The in-place penetration test, which is designed to yield equivalent penetration measurements as the standard DOP efficiency test, is based on measuring the aerosol penetration of the filter installation as a function of particle size using a portable laser particle counter. This in-place penetration test is compared to the current in-place leak test using light scattering photometers for single HEPA filter installations and for HEPA filter plenums using the shroud method. Test results show the in-place penetration test is more sensitive than the in-place leak test, has a similar operating procedure, but takes longer to conduct. Additional tests are required to confirm that the in-place penetration test yields identical results as the standard dioctyl phthalate (DOP) penetration test for HEPA filters with controlled leaks in the filter and gasket and duct by-pass leaks. Further development of the procedure is also required to reduce the test time before the in-place penetration test is practical. 14 refs., 14 figs., 3 tabs.

  17. Cyclic dipeptide based cell-penetrating peptidomimetics for effective DNA delivery.

    Science.gov (United States)

    Madhu, Chilakapati; Voshavar, Chandrashekhar; Rajasekhar, K; Govindaraju, Thimmaiah

    2017-04-11

    An unnatural CDP-amino acid (kd) is used in the design and synthesis of novel cell penetrating peptidomimetic (Kkd-5). The balanced cationic nature and structural rigidity of Kkd-5 resulted in serum stability, non-toxicity to cells, and interaction with membrane and DNA, all of which facilitated efficient cellular uptake and DNA delivery.

  18. Influence of jet thrust on penetrator penetration when studying the structure of space object blanket

    Directory of Open Access Journals (Sweden)

    N. A. Fedorova

    2014-01-01

    Full Text Available The article presents the calculation-and-theory-based research results to examine the possibility for using the jet thrust impulse to increase a penetration depth of high-velocity penetrator modules. Such devices can be used for studies of Earth surface layer composition, and in the nearest future for other Solar system bodies too. Research equipment (sensors and different instruments is housed inside a metal body of the penetrator with a sharpened nose that decreases drag force in soil. It was assumed, that this penetrator is additionally equipped with the pulse jet engine, which is fired at a certain stage of penetrator motion into target.The penetrator is considered as a rigid body of variable mass, which is subjected to drag force and reactive force applied at the moment the engine fires. A drag force was represented with a binomial empirical law, and penetrator nose part was considered to be conical. The jet thrust force was supposed to be constant during its application time. It was in accordance with assumption that mass flow and flow rate of solid propellant combustion products were constant. The amount of propellant in the penetrator was characterized by Tsiolkovsky number Z, which specifies the ratio between the fuel mass and the penetrator structure mass with no fuel.The system of equations to describe the penetrator dynamics was given in dimensionless form using the values aligned with penetration of an equivalent inert penetrator as the time and penetration depth scales. Penetration dynamics of penetrator represented in this form allowed to eliminate the influence of penetrator initial mass and its cross-section diameter on the solution results. The lack of such dependency is convenient for comparing the calculation results since they hold for penetrators of various initial masses and cross-sections.To calculate the penetration a lunar regolith was taken as a soil material. Calculations were carried out for initial velocities of

  19. On the analysis of well test data influenced by wellbore storage skin and bottom water drive

    Energy Technology Data Exchange (ETDEWEB)

    Chu, W.C.; Reynolds, A.C.; Raghavan, R.

    1981-01-01

    This paper discusses procedures to analyze pressure data in partially penetrating wells influenced by storage and skin effects. The effect of a gas cap or a bottom-water aquifer is also documented. Type curves are presented to analyze data influenced by storage, skin, partial penetration, and the influence of a constant pressure boundary. The main advantage of this work is that anisotropy (ratio of horizontal to vertical permeability) and penetration ratio are incorporated in a simple way. Procedures to minimize the problems of obtaining a unique type curve matching are also discussed. 16 refs.

  20. Facilitating Understandings of Geometry.

    Science.gov (United States)

    Pappas, Christine C.; Bush, Sara

    1989-01-01

    Illustrates some learning encounters for facilitating first graders' understanding of geometry. Describes some of children's approaches using Cuisenaire rods and teacher's intervening. Presents six problems involving various combinations of Cuisenaire rods and cubes. (YP)

  1. Facilitating Knowledge Sharing

    DEFF Research Database (Denmark)

    Holdt Christensen, Peter

    Abstract This paper argues that knowledge sharing can be conceptualized as different situations of exchange in which individuals relate to each other in different ways, involving different rules, norms and traditions of reciprocity regulating the exchange. The main challenge for facilitating...... and the intermediaries regulating the exchange, and facilitating knowledge sharing should therefore be viewed as a continuum of practices under the influence of opportunistic behaviour, obedience or organizational citizenship behaviour. Keywords: Knowledge sharing, motivation, organizational settings, situations...

  2. Modulating the skin barrier function by DMSO: molecular dynamics simulations of hydrophilic and hydrophobic transmembrane pores

    NARCIS (Netherlands)

    den Otter, Wouter K.; Notman, R.; Anwar, J.; Noro, M.G.; Briels, Willem J.

    2008-01-01

    The dense lipid bilayers at the outer surface of the skin represent the primary barrier to molecules penetrating the human skin. One approach to overcome this barrier, with promising applications in administering medicinal drugs to the body, is to employ chemical permeability enhancers. How these

  3. Modulating the skin barrier function by DMSO: molecular dynamics simulations of hydrophilic and hydrophobic transmembrane pores

    NARCIS (Netherlands)

    Otter, den W.K.; Notman, R.; Anwar, J.; Noro, M.G.; Briels, W.J.

    2008-01-01

    The dense lipid bilayers at the outer surface of the skin represent the primary barrier to molecules penetrating the human skin. One approach to overcome this barrier, with promising applications in administering medicinal drugs to the body, is to employ chemical permeability enhancers. How these en

  4. Modulating the skin barrier function by DMSO: molecular dynamics simulations of hydrophilic and hydrophobic transmembrane pores

    NARCIS (Netherlands)

    den Otter, Wouter K.; Notman, R.; Anwar, J.; Noro, M.G.; Briels, Willem J.

    2008-01-01

    The dense lipid bilayers at the outer surface of the skin represent the primary barrier to molecules penetrating the human skin. One approach to overcome this barrier, with promising applications in administering medicinal drugs to the body, is to employ chemical permeability enhancers. How these en

  5. Advancements in the maintenance of skin barrier/skin lipid composition and the involvement of metabolic enzymes.

    Science.gov (United States)

    Cui, Le; Jia, Yan; Cheng, Zhi-Wei; Gao, Ying; Zhang, Gao-Lei; Li, Jing-Yi; He, Cong-Fen

    2016-12-01

    The human skin barrier has an important role in protection and defense, reflected not only in the ability to resist entry of harmful substances into the human body, but also in the ability to prevent loss of water and nutrients. Once the skin barrier is damaged, the skin may become dry, scaly, and wrinkled, and a series of skin problems may occur. In this article, we review the composition of lipids, such as ceramides, cholesterol, and free fatty acids, in the skin and examine the expression of enzymes related to lipid metabolism, such as kallikreins, elongase of elongation of very long-chain fatty acids, hydrolases, and lipid synthases. Additionally, we discuss the involvement of these proteins in skin barrier function and structure. The information presented in this review is expected to provide a theoretical basis for the development of skin care products facilitating the maintenance and repair of skin barrier function. © 2016 Wiley Periodicals, Inc.

  6. Freeze-drying as a preserving preparation technique for in vitro testing of human skin.

    Science.gov (United States)

    Franzen, Lutz; Vidlářová, Lucie; Kostka, Karl-Heinz; Schaefer, Ulrich F; Windbergs, Maike

    2013-01-01

    In vitro testing of drugs with excised human skin is a valuable prerequisite for clinical studies. However, the analysis of excised human skin presents several obstacles. Ongoing drug diffusion, microbial growth and changes in hydration state influence the results of drug penetration studies. In this work, we evaluate freeze-drying as a preserving preparation method for skin samples to overcome these obstacles. We analyse excised human skin before and after freeze-drying and compare these results with human skin in vivo. Based on comprehensive thermal and spectroscopic analysis, we demonstrate comparability to in vivo conditions and exclude significant changes within the skin samples due to freeze-drying. Furthermore, we show that freeze-drying after skin incubation with drugs prevents growth of drug crystals on the skin surface due to drying effects. In conclusion, we introduce freeze-drying as a preserving preparation technique for in vitro testing of human skin.

  7. Evaluation of skin viability effect on ethosome and liposome-mediated psoralen delivery via cell uptake.

    Science.gov (United States)

    Zhang, Yong-Tai; Shen, Li-Na; Wu, Zhong-Hua; Zhao, Ji-Hui; Feng, Nian-Ping

    2014-10-01

    This study investigated the effect of skin viability on its permeability to psoralen delivered by ethosomes, as compared with liposomes. With decreasing skin viability, the amount of liposome-delivered psoralen that penetrated through the skin increased, whereas skin deposition of psoralen from both ethosomes and liposomes reduced. Psoralen delivery to human-immortalized epidermal cells was more effective using liposomes, whereas delivery to human embryonic skin fibroblast cells was more effective when ethosomes were used. These findings agreed with those of in vivo studies showing that skin psoralen deposition from ethosomes and liposomes first increased and then plateaued overtime, which may indicate gradual saturation of intracellular drug delivery. It also suggested that the reduced deposition of ethosome- or liposome-delivered psoralen in skin with reduced viability may relate to reduced cellular uptake. This work indicated that the effects of skin viability should be taken into account when evaluating nanocarrier-mediated drug skin permeation.

  8. Topically applied ceramide accumulates in skin glyphs

    Directory of Open Access Journals (Sweden)

    Zhang Q

    2015-07-01

    Full Text Available Qihong Zhang,1 Carol R Flach,1 Richard Mendelsohn,1 Guangru Mao,2 Apostolos Pappas,2 M Catherine Mack,2 Russel M Walters,2 Michael D Southall2 1Department of Chemistry, Rutgers University, Newark, 2Johnson & Johnson Consumer Companies, Inc., Skillman, NJ, USAAbstract: Ceramides (CERs, structural components of the stratum corneum (SC, impart essential barrier properties to this thin outer layer of the epidermis. Variations in CER species within this layer have been linked to several skin diseases. A recent proliferation of CER-containing topical skin-care products warrants the elucidation of CER penetration profiles in both healthy and diseased skin. In the current study, the spatial distributions of CER concentration profiles, following topical application of two species of CER, were tracked using infrared imaging. Suspensions of single-chain perdeuterated sphingosine and phytosphingosine CER in oleic acid were applied, in separate experiments, to the surface of healthy intact ex vivo human skin using Franz diffusion cells. Following either a 24- or 48-hour incubation period at 34°C, infrared images were acquired from microtomed skin sections. Both CER species accumulated in glyph regions of the skin and penetrated into the SC, to a limited extent, only in these regions. The concentration profiles observed herein were independent of the CER species and incubation time utilized in the study. As a result, a very heterogeneous, sparse, spatial distribution of CERs in the SC was revealed. In contrast, oleic acid was found to be fairly homogeneously distributed throughout the SC and viable epidermis, albeit at lower concentrations in the latter. A more uniform, lateral distribution of CERs in the SC would likely be important for barrier efficacy or enhancement.Keywords: stratum corneum, infrared imaging, topical delivery, oleic acid

  9. Predicting human epidermal melanin concentrations for different skin tones

    CSIR Research Space (South Africa)

    Smit, Jacoba E

    2011-07-01

    Full Text Available In the past 50 years lasers has found numerous applications in medicine. One of their advantages is their use for minimalistic or non-invasive diagnosis and treatment. Often that means light penetration through skin and the correct dose required...

  10. Phosphatidylcholine embedded micellar systems: enhanced permeability through rat skin.

    Science.gov (United States)

    Spernath, Aviram; Aserin, Abraham; Sintov, Amnon C; Garti, Nissim

    2008-02-15

    Micellar and microemulsion systems are excellent potential vehicles for delivery of drugs because of their high solubilization capacity and improved transmembrane bioavailability. Mixtures of propylene glycol (PG) and nonionic surfactants with sodium diclofenac (DFC) were prepared in the presence of phosphatidylcholine (PC) as transmembrane transport enhancers. Fully dilutable systems with maximum DFC solubilization capacity (SC) at pH 7 are presented. It was demonstrated that the concentrates underwent phase transitions from reverse micelles to swollen reverse micelles and, via the bicontinuous transitional mesophase, into inverted O/W microstructures. The SC decreases as a function of dilution. DFC transdermal penetration using rat skin in vitro correlated with SC, water content, effect of phospholipid content, presence of an oil phase, and ethanol. Skin penetration from the inverted bicontinuous mesophase and the skin penetration from the O/W-like microstructure were higher than that measured from the W/O-like droplets, especially when the micellar system containing the nonionic surfactant, sugar ester L-1695, and hexaglycerol laurate. PC embedded within the micelle interface significantly increased the penetration flux across the skin compared to micellar systems without the embedded PC at their interface. Moreover, the combination of PC with HECO40 improved the permeation rate (P) and shortened the lag-time (T(L)).

  11. Safety evaluation of topical applications of ethanol on the skin and inside the oral cavity

    Directory of Open Access Journals (Sweden)

    Lachenmeier Dirk W

    2008-11-01

    Full Text Available Abstract Ethanol is widely used in all kinds of products with direct exposure to the human skin (e.g. medicinal products like hand disinfectants in occupational settings, cosmetics like hairsprays or mouthwashes, pharmaceutical preparations, and many household products. Contradictory evidence about the safety of such topical applications of the alcohol can be found in the scientific literature, yet an up-to-date risk assessment of ethanol application on the skin and inside the oral cavity is currently lacking. The first and foremost concerns of topical ethanol applications for public health are its carcinogenic effects, as there is unambiguous evidence for the carcinogenicity of ethanol orally consumed in the form of alcoholic beverages. So far there is a lack of evidence to associate topical ethanol use with an increased risk of skin cancer. Limited and conflicting epidemiological evidence is available on the link between the use of ethanol in the oral cavity in the form of mouthwashes or mouthrinses and oral cancer. Some studies pointed to an increased risk of oral cancer due to locally produced acetaldehyde, operating via a similar mechanism to that found after alcoholic beverage ingestion. In addition, topically applied ethanol acts as a skin penetration enhancer and may facilitate the transdermal absorption of xenobiotics (e.g. carcinogenic contaminants in cosmetic formulations. Ethanol use is associated with skin irritation or contact dermatitis, especially in humans with an aldehyde dehydrogenase (ALDH deficiency. After regular application of ethanol on the skin (e.g. in the form of hand disinfectants relatively low but measurable blood concentrations of ethanol and its metabolite acetaldehyde may occur, which are, however, below acute toxic levels. Only in children, especially through lacerated skin, can percutaneous toxicity occur. As there might be industry bias in many studies about the safety of topical ethanol applications, as well

  12. Penetrating Moral Education in English Teaching

    Institute of Scientific and Technical Information of China (English)

    汪中跃

    2015-01-01

    Middle school students’ moral education is not ful y implemented or even ignored in the present English teaching,so in this paper,the importance of penetrating the cultivation of middle school students’ moral education in English teaching is analyzed,the strategies of penetrating moral education are discussed and the significance is also pointed out.

  13. Quantitative penetration testing with item response theory

    NARCIS (Netherlands)

    Arnold, Florian; Pieters, Wolter; Stoelinga, Mariëlle

    2014-01-01

    Existing penetration testing approaches assess the vulnerability of a system by determining whether certain attack paths are possible in practice. Thus, penetration testing has so far been used as a qualitative research method. To enable quantitative approaches to security risk management, including

  14. Quantitative penetration testing with item response theory

    NARCIS (Netherlands)

    Pieters, W.; Arnold, F.; Stoelinga, M.I.A.

    2013-01-01

    Existing penetration testing approaches assess the vulnerability of a system by determining whether certain attack paths are possible in practice. Therefore, penetration testing has thus far been used as a qualitative research method. To enable quantitative approaches to security risk management, in

  15. Quantitative penetration testing with item response theory

    NARCIS (Netherlands)

    Arnold, Florian; Pieters, Wolter; Stoelinga, Mariëlle

    2013-01-01

    Existing penetration testing approaches assess the vulnerability of a system by determining whether certain attack paths are possible in practice. Thus, penetration testing has so far been used as a qualitative research method. To enable quantitative approaches to security risk management, including

  16. Endoscopic biopsy: Duodenal ulcer penetrating into liver

    Institute of Scientific and Technical Information of China (English)

    Baybora Kircali; Tülay Saricam; Aysegul Ozakyol; Eser Vardareli

    2005-01-01

    @@ TO THE EDITOR We have read with interest the recent report by E Kayacetin and S Kayacetin of Gastric ulcer penetrating to liver diagnosed by endoscopic biopsy[1] since we diagnosed the duodenal ulcer which penetrated into liver similarly. This is a rather unusual case because of the fifth case in the literature and responding to medical therapy.

  17. Efficient Calculation of Earth Penetrating Projectile Trajectories

    Science.gov (United States)

    2006-09-01

    CALCULATION OF EARTH PENETRATING PROJECTILE TRAJECTORIES by Daniel F . Youch September 2006 Thesis Advisor: Joshua Gordis... Daniel F . Youch 5. FUNDING NUMBERS 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Naval Postgraduate School Monterey, CA 93943-5000 8. PERFORMING...EFFICIENT CALCULATION OF EARTH PENETRATING PROJECTILE TRAJECTORIES Daniel F . Youch Lieutenant Commander, United States Navy B.S., Temple

  18. Skin Exposure and Asthma: Is There a Connection?

    OpenAIRE

    Redlich, Carrie A.

    2010-01-01

    Numerous occupational and environmental exposures that increase asthma risk have been identified. Research and prevention have focused primarily on the respiratory tract. However, recent studies suggest that the skin may also be an important route of exposure and site of sensitization that contributes to asthma development. Factors that impair skin barrier function, such as filaggrin gene mutations or skin trauma, may facilitate allergen entry and promote Th2-like sensitization and subsequent...

  19. Skin Delivery of Hydrophilic Biomacromolecules Using Marine Sponge Spicules.

    Science.gov (United States)

    Zhang, Saiman; Ou, Huilong; Liu, Chunyun; Zhang, Yuan; Mitragotri, Samir; Wang, Dexiang; Chen, Ming

    2017-09-05

    We report the development of sponge Haliclona sp. spicules, referred to as SHS, and its topical application in skin delivery of hydrophilic biomacromolecules, a series of fluorescein isothiocyanate-dextrans (FDs). SHS are silicious oxeas which are sharp-edged and rod-shaped (∼120 μm in length and ∼7 μm in diameter). SHS can physically disrupt skin in a dose-dependent manner and retain within the skin over at least 72 h, which allows sustained skin penetration of hydrophilic biomacromolecules. The magnitude of enhancement of FD delivery into skin induced by SHS treatment was dependent on its molecular weight. Specifically, SHS topical application enhanced FD-10 (MW: 10 kDa) penetration into porcine skin in vitro by 33.09 ± 7.16-fold compared to control group (p < 0.01). SHS dramatically increased the accumulation of FD-10 into and across the dermis by 62.32 ± 13.48-fold compared to the control group (p < 0.01). In vivo experiments performed using BALB/c mice also confirmed the effectiveness of SHS topical application; the skin absorption of FD-10 with SHS topical application was 72.14 ± 48.75-fold (p < 0.05) and 15.39 ± 9.91-fold (p < 0.05) higher than those from the PBS and Dermaroller microneedling, respectively. Further, skin irritation study and transepidermal water loss (TEWL) measurement using guinea pig skin in vivo indicated that skin disruption induced by SHS treatment is self-limited and can be recovered with time and efficiently. SHS can offer a safe, effective, and sustained skin delivery of hydrophilic biomacromolecules and presents a promising platform technology for a wide range of cosmetic and medical applications.

  20. Skin Care and Aging

    Science.gov (United States)

    ... version of this page please turn Javascript on. Skin Care and Aging How Aging Affects Skin Your skin changes with age. It becomes thinner, ... to make it feel and look better. Dry Skin and Itching Click for more information Many older ...

  1. Consistent wind Facilitates Vection

    Directory of Open Access Journals (Sweden)

    Masaki Ogawa

    2011-10-01

    Full Text Available We examined whether a consistent haptic cue suggesting forward self-motion facilitated vection. We used a fan with no blades (Dyson, AM01 providing a wind of constant strength and direction (wind speed was 6.37 m/s to the subjects' faces with the visual stimuli visible through the fan. We used an optic flow of expansion or contraction created by positioning 16,000 dots at random inside a simulated cube (length 20 m, and moving the observer's viewpoint to simulate forward or backward self-motion of 16 m/s. we tested three conditions for fan operation, which were normal operation, normal operation with the fan reversed (ie, no wind, and no operation (no wind and no sound. Vection was facilitated by the wind (shorter latency, longer duration and larger magnitude values with the expansion stimuli. The fan noise did not facilitate vection. The wind neither facilitated nor inhibited vection with the contraction stimuli, perhaps because a headwind is not consistent with backward self-motion. We speculate that the consistency between multi modalities is a key factor in facilitating vection.

  2. Measurement of optical penetration depth and refractive index of human tissue

    Institute of Scientific and Technical Information of China (English)

    Shusen Xie(谢树森); Hui Li(李晖); Buhong Li(李步洪)

    2003-01-01

    Experimental techniques for measurement of optical penetration depth and refractive index of human tissue are presented, respectively. Optical penetration depth can be obtained from the measurement of the relative fluence-depth distribution inside the target tissue. The depth of normal and carcinomatous human lung tissues irradiated with the wavelengths of 406.7, 632.8 and 674.4 nm in vitro are respectively determined. In addition, a novel simple method based on total internal reflection for measuring the refractive index of biotissue in vivo is developed, and the refractive indices of skin from people of different age, sex and skin color are measured. Their refractive indices are almost same and the average is 1.533.

  3. FINITE ELEMENT METHOD ON NUMERICAL SIMULATION OF STRATUM CORNEUM'S PENETRATION PROPERTY

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    How the outer substance could penetrate through the skin lies in the stratum corneum, because it is the main barrier in the multi-layers of the skin. Supposing the keratin cell with a special geometry as tetrakaidecahedron, the penetration property of stratum corneum was the key problem which was numerically simulated with finite element method. At first the discretization of the stratum corneum region was given in two steps: first, the discretization of the keratin cell; second, the discretization of fattiness that surrounds the keratin. Then there was the work of numerical simulation. In this procedure, the finite element method and the multi-grid method were used. The former was to obtain the discretization of basic elements; the latter was to decrease the high frequency error. At last the visualization of the numerical simulation was shown.

  4. Effect of occlusion on the percutaneous penetration of linoleic acid and glycerol.

    Science.gov (United States)

    Taylor, Louise J; Lee, Robert S; Long, Mark; Rawlings, Anthony V; Tubek, Joseph; Whitehead, Lynne; Moss, Gary P

    2002-12-05

    The effect of occlusion on the in vitro percutaneous absorption of linoleic acid was investigated. A greater skin concentration of linoleic acid from an ethanolic vehicle was observed in non-occluded experiments compared with occluded experiments (Pcyclomethicone). These observations were attributed to the increase in the concentration gradient due to the unimpeded evaporation of volatile solvents, which provided a greater driving force and enhanced non-occluded delivery in these systems, compared with occluded systems. Conversely, the percutaneous absorption of a polar material (glycerol) from an aqueous solution did not yield any such differences. While more conclusive comparisons between volatile and non-volatile solvents and penetrants would be required to substantiate fully these comparisons, it is apparent that non-occlusion of volatile solvents may enhance percutaneous absorption. The physicochemical properties of the penetrant, for example its natural state at skin temperature (i.e. solid or liquid) may further determine the degree of enhanced percutaneous absorption compared with occluded environments.

  5. Curcumin loaded chitin nanogels for skin cancer treatment via the transdermal route

    Science.gov (United States)

    Mangalathillam, Sabitha; Rejinold, N. Sanoj; Nair, Amrita; Lakshmanan, Vinoth-Kumar; Nair, Shantikumar V.; Jayakumar, Rangasamy

    2011-12-01

    In this study, curcumin loaded chitin nanogels (CCNGs) were developed using biocompatible and biodegradable chitin with an anticancer curcumin drug. Chitin, as well as curcumin, is insoluble in water. However, the developed CCNGs form a very good and stable dispersion in water. The CCNGs were analyzed by DLS, SEM and FTIR and showed spherical particles in a size range of 70-80 nm. The CCNGs showed higher release at acidic pH compared to neutral pH. The cytotoxicity of the nanogels were analyzed on human dermal fibroblast cells (HDF) and A375 (human melanoma) cell lines and the results show that CCNGs have specific toxicity on melanoma in a concentration range of 0.1-1.0 mg mL-1, but less toxicity towards HDF cells. The confocal analysis confirmed the uptake of CCNGs by A375. The apoptotic effect of CCNGs was analyzed by a flow-cytometric assay and the results indicate that CCNGs at the higher concentration of the cytotoxic range showed comparable apoptosis as the control curcumin, in which there was negligible apoptosis induced by the control chitin nanogels. The CCNGs showed a 4-fold increase in steady state transdermal flux of curcumin as compared to that of control curcumin solution. The histopathology studies of the porcine skin samples treated with the prepared materials showed loosening of the horny layer of the epidermis, facilitating penetration with no observed signs of inflammation. These results suggest that the formulated CCNGs offer specific advantage for the treatment of melanoma, the most common and serious type of skin cancer, by effective transdermal penetration.

  6. Deformable liposomes and ethosomes: mechanism of enhanced skin delivery.

    Science.gov (United States)

    Elsayed, Mustafa M A; Abdallah, Ossama Y; Naggar, Viviane F; Khalafallah, Nawal M

    2006-09-28

    Despite intensive research, the mechanisms by which vesicular systems deliver drugs into intact skin are not yet fully understood. In the current study, possible mechanisms by which deformable liposomes and ethosomes improve skin delivery of ketotifen under non-occlusive conditions were investigated. In vitro permeation and skin deposition behavior of deformable liposomes and ethosomes, having ketotifen both inside and outside the vesicles (no separation of free ketotifen), having ketotifen only inside the vesicles (free ketotifen separated) and having ketotifen only outside the vesicles (ketotifen solution added to empty vesicles), was studied using rabbit pinna skin. Results suggested that both the penetration enhancing effect and the intact vesicle permeation into the stratum corneum might play a role in improving skin delivery of drugs by deformable liposomes, under non-occlusive conditions, and that the penetration enhancing effect was of greater importance in case of ketotifen. Regarding ethosomes, results indicated that ketotifen should be incorporated in ethosomal vesicles for optimum skin delivery. Ethosomes were not able to improve skin delivery of non-entrapped ketotifen.

  7. Subcutaneous emphysema of the upper extremity following penetrating blackthorn injury to the wrist.

    LENUS (Irish Health Repository)

    Tiong, W H C

    2009-02-01

    SUMMARY: Noninfective subcutaneous emphysema of the upper extremity, albeit rare, has to be borne in mind when treating patients with subcutaneous emphysema. The misdiagnosis of this condition as its serious infective counterpart often leads to unnecessary aggressive treatment. Noninfective subcutaneous emphysema often accompanies a patient who has no systemic symptoms of illness. Unfortunately, the distinction is not always easy especially when history of injury suggests involvement of an infective or reactive element. Penetrating blackthorn injury is common, especially in rural communities, and often occurs from farming or gardening activities. Blackthorn penetration can cause numerous tissue reactions once embedded under the skin and they are often contaminated with soil. Here we present, for the first time, a case where penetrating blackthorn injury to the wrist resulted in noninfective subcutaneous emphysema involving the whole upper limb and neck, and its subsequent management.

  8. In Vitro and In Vivo Measurement of Percutaneous Penetration of Low Molecular Weight Toxins of Military Interest

    Science.gov (United States)

    1990-10-21

    Penetration of nonelectrolytes (alcohols) from aqueous solutions and from pure liquids. J. Invest Dermato , 60: 286-296. 8. Franz T.J. (1975) Percutaneous...Absorption. On the relevance of in vitro data. J. Invest Dermato 64: 190-195. 43 IN VITRO FLOW-THROUGH DIFFUSION CELL f f Skin -M~Naterial -Fluid "P

  9. Transconjunctival penetration of mitomycin C

    Directory of Open Access Journals (Sweden)

    Velpandian T

    2008-01-01

    Full Text Available Aims: The study was performed to estimate transconjunctival penetration of mitomycin C (MMC to Tenon′s tissue following application over the intact conjunctiva before routine trabeculectomy. Settings and Design: Institution-based case series. Materials and Methods: In 41 eyes of 41 patients, MMC (0.4 mg/ml for 3 min was applied over the intact conjunctiva before beginning trabeculectomy. Tenon′s capsule directly beneath the site of application was excised during trabeculectomy and was homogenized, centrifuged and MMC concentrations were analyzed using high-performance liquid chromatography (HPLC. Statistical Analysis Used: Statistical analysis was performed using stata0 8.0 version software (STATA Corporation, Houston, TX, USA. In this study, P -values less than 0.05 were considered as statistically significant. Results: The average weight of the sample of Tenon′s tissue excised was 5.51 ± 4.42 mg (range: 0.9-17.1 and the average estimated MMC concentration found to be present in Tenon′s tissue using HPLC was 18.67 ± 32.36 x 10−6 moles/kg of the tissue (range: 0.38-197.05 x 10−6 . In 36 of the 41 patients (87.80%, the MMC concentration reached above 2 x 10−6 moles/kg of the tissue concentration required to inhibit human conjunctival fibroblasts. Conclusions: Mitomycin C does permeate into the subconjunctival tissue after supraconjunctival application for 3 min. Application of MMC over the conjunctiva may be a useful alternative to subconjunctival or subscleral application during routine trabeculectomy and as an adjunct for failing blebs.

  10. Noncontacting diffuse VIS-NIR spectroscopy of human skin for evaluation of skin type and time-dependent microcirculation

    Science.gov (United States)

    Schmidt, Wolf-Dieter; Fassler, Dieter; Zimmermann, Gabi; Liebold, Kristin; Wollina, Uwe

    2000-11-01

    Spectroscopic investigations of the VIS-NIR range allow the objective determination of pigmentation, blood microcirculation and water content of human skin. Non- contacting in vivo measurements of the human skin of 50 volunteers reflect the clinical skin type well. Our correlation analysis yields that the red/infrared spectral range can be used for a determination of skin type. The observed strong spectral variations within the same group of skin type are likely based on the high biological variability of human skin and subjective clinically observed skin type. Therefore it can be useful to measure the full spectral range and to calculate a non-observed skin score with multivariate spectral methods. By multivariate analysis a correct classification of remittance spectra can be obtained. Time- depending spectral variations of dermal microcirculation can be measured at defined locations of the body, for instance the dynamics of oxygenation or blood volume in the skin of the fingertip. The cardial, pulmonal and vasomotoric waves of the micro- and macrocirculation are clearly visible at different wavelengths. The spectroscopic informations are important as an objective measure for the skin type evaluation, the penetration behavior of pharmaca, laser surgery, and therapy.

  11. Influence of hydroxypropyl-beta-cyclodextrin on transdermal penetration and photostability of avobenzone.

    Science.gov (United States)

    Yang, Jing; Wiley, Cody J; Godwin, Donald A; Felton, Linda A

    2008-06-01

    The objective of the present study was to determine the effects of hydroxypropyl-beta-cyclodextrin (HPCD) complexation on the transdermal penetration and photostability of a model ultraviolet A (UVA) absorber, butyl methoxydibenzoylmethane (avobenzone), and to determine the influence of complexation on in vivo photoprotection. Avobenzone-HPCD complexation was demonstrated by differential scanning calorimetry. Formulations containing 0.12 mg/ml avobenzone and up to 30% (w/w) HPCD were prepared. Transdermal penetration was conducted using a modified Franz diffusion cell apparatus. As the concentration of HPCD was increased from 0% to 20%, transdermal permeation increased. Maximum flux occurred at 20% HPCD, where sufficient cyclodextrin was present to completely solubilize all avobenzone. When the concentration of HPCD was increased to 30%, transdermal penetration decreased, suggesting the formation of an avobenzone reservoir on the skin surface. Photostability of avobenzone was investigated under 100, 250, and 500 kJ/m2 UVA irradiation. The 30% HPCD formulation was the most photostable, followed by 20%, 10%, and 0% formulations. In vivo, the 30% HPCD formulation afforded the best photoprotection, as evidenced by the lowest extent of sunburn cell formation and edema induction. This work indicates that inclusion of HPCD in sunscreen formulations may enhance photoprotection by reducing both skin penetration and photodecomposition of UV absorbers.

  12. Penetration enhancing effects of selected natural oils utilized in topical dosage forms.

    Science.gov (United States)

    Viljoen, Joe M; Cowley, Amé; du Preez, Jan; Gerber, Minja; du Plessis, Jeanetta

    2015-01-01

    Various natural products, including oils, have been utilized as penetration enhancers due to their "safety profiles". These oils contain fatty acids promoting skin permeability through lipid fluidization within the stratum corneum; and might therefore be able to effectively enhance transdermal drug delivery. We investigated possible penetration enhancing properties of selected oils, utilizing flurbiprofen as marker compound in emulgel formulations. The formulations were compared to a liquid paraffin emulgel and a hydrogel to establish any significant penetration enhancing effects. Gas chromatographic analysis of the natural oils was performed at ambient temperature to determine the fatty acid composition in each selected natural oils. Franz cell diffusion studies and tape stripping methods were employed to study delivery of the marker into, and through the skin. The following rank order for the emulgel flux-values was obtained: Hydrogel > olive oil > liquid paraffin > coconut oil > grape seed oil > Avocado oil ≥ Crocodile oil > Emu oil. Results suggested that oils containing predominantly mono-unsaturated oleic acid, on average increased the flux of the marker to a larger extent than oils containing an almost even mixture of both mono- and poly-unsaturated fatty acids. Oils comprising saturated fatty acids (SFAs) with alkyl chains between C12 and C14, increased the marker flux to a higher extent than oils containing C16-C18 SFAs. Effects observed for branched fatty acids, however, did not vary significantly from effects for unbranched fatty acids with the same carbon chain length. Natural oils possess penetration enhancing effects.

  13. Penetration enhancer-containing vesicles (PEVs) as carriers for cutaneous delivery of minoxidil: in vitro evaluation of drug permeation by infrared spectroscopy.

    Science.gov (United States)

    Mura, Simona; Manconi, Maria; Fadda, Anna Maria; Sala, Maria Chiara; Perricci, Jacopo; Pini, Elena; Sinico, Chiara

    2013-01-01

    Recently, we carried out a research on new liposomal systems prepared by using in their composition a few penetration enhancers which differ for chemical structure and physicochemical properties. The penetration enhancer-containing vesicles (PEVs) were prepared by using soy lecithin and different amounts of three penetration enhancers, 2-(2-ethoxyethoxy) ethanol (Transcutol(®)), capryl-caproyl macrogol 8-glyceride (Labrasol(®)), and cineole.To study the influence of the PEVs on (trans)dermal delivery of minoxidil, in vitro diffusion experiments were performed through new born pig skin and the results were compared with that obtained applying the vesicular system without enhancer (control) after pretreatment of the skin with the various enhancers. In this study, Fourier transform infrared spectroscopy (FTIR), attenuated total reflectance FTIR (ATR-FTIR) and FTIR imaging were used to evaluate the effective penetration of minoxidil in the skin layers and to discover the influence of the enhancer on the drug topical delivery. These analytical studies allowed us to characterize the drug formulations and to evaluate the vesicle distribution into the skin. Recorded spectra confirmed that the vesicle formulations with penetration enhancers promoted drug deposition into the skin.

  14. Modeling pollutant penetration across building envelopes

    Energy Technology Data Exchange (ETDEWEB)

    Liu, De-Ling; Nazaroff, William W.

    2001-04-01

    As air infiltrates through unintentional openings in building envelopes, pollutants may interact with adjacent surfaces. Such interactions can alter human exposure to air pollutants of outdoor origin. We present modeling explorations of the proportion of particles and reactive gases (e.g., ozone) that penetrate building envelopes as air enters through cracks and wall cavities. Calculations were performed for idealized rectangular cracks, assuming regular geometry, smooth inner crack surface and steady airflow. Particles of 0.1-1.0 {micro}m diameter are predicted to have the highest penetration efficiency, nearly unity for crack heights of 0.25 mm or larger, assuming a pressure difference of 4 Pa or greater and a flow path length of 3 cm or less. Supermicron and ultrafine particles are significantly removed by means of gravitational settling and Brownian diffusion, respectively. In addition to crack geometry, ozone penetration depends on its reactivity with crack surfaces, as parameterized by the reaction probability. For reaction probabilities less than {approx}10{sup -5}, penetration is complete for cracks heights greater than 1 mm. However, penetration through mm scale cracks is small if the reaction probability is {approx}10{sup -4} or greater. For wall cavities, fiberglass insulation is an efficient particle filter, but particles would penetrate efficiently through uninsulated wall cavities or through insulated cavities with significant airflow bypass. The ozone reaction probability on fiberglass fibers was measured to be 10{sup -7} for fibers previously exposed to high ozone levels and 6 x 10{sup -6} for unexposed fibers. Over this range, ozone penetration through fiberglass insulation would vary from >90% to {approx}10-40%. Thus, under many conditions penetration is high; however, there are realistic circumstances in which building envelopes can provide substantial pollutant removal. Not enough is yet known about the detailed nature of pollutant penetration

  15. Facilitation skills for trainers

    Directory of Open Access Journals (Sweden)

    F. Cilliers

    2000-06-01

    Full Text Available This research aims to develop the facilitation skills of trainers. Facilitation is defined form the Person-Centered approach, as providing an opportunity for the trainee to experience personal growth and learning. A facilitation skills workshop was presented to 40 trainers, focussing on enhancing selfactualisation, its intra and inter personal characteristics, and attending and responding behaviour. Measurement with the Personal Orientation Inventory and Carkhuff scales, indicate enhanced cognitive, affective and conative sensitivity and interpersonal skills. A post-interview indicates the trainers experienced empowerment in dealing with the providing of opportunities for growth amongst trainees, in all kinds of training situations. Recommendations are made to enhance facilitation development amongst trainers. Opsomming Hierdie navorsing poog om die fasiliteringsvaardighede van opieiers te ontwikkel. Fasilitering word gedefinieer vanuit die Persoonsgesentreerde benadering as die beskikbaarstelling van 'n geleentheid om persoonlike groei en leer te ervaar. 'n Fasiliteringsvaardighede werkswinkel is aangebied vir 40 opieiers, met die fokus op die stimulering van selfaktualisering, die intra en interpersoonlike kenmerke daarvan, en aandagskenk- en responderings- gedrag. Meting met die Persoonlike Orientasievraelys en die Carkhuff skale, dui op n toename in kognitiewe, affektiewe en konatiewe sensitiwiteit en interpersoonlike vaardighede. n Post-onderhoud dui op die opleier se ervaarde bemagtiging in die beskikbaarstelling van groeigeleenthede vir opleidelinge, in all tipe opleidingsituasies. Aanbevelings word gemaak om die ontwikkeling van fasiliteringsvaardighede by opleiers te verhoog.

  16. From Teaching to Facilitation

    DEFF Research Database (Denmark)

    de Graaff, Erik

    2013-01-01

    A shift from teaching to learning is characteristic of the introduction of Problem Based Learning (PBL) in an existing school. As a consequence the teaching staff has to be trained in skills like facilitating group work and writing cases. Most importantly a change in thinking about teaching...

  17. Facilitation of Adult Development

    Science.gov (United States)

    Boydell, Tom

    2016-01-01

    Taking an autobiographical approach, I tell the story of my experiences facilitating adult development, in a polytechnic and as a management consultant. I relate these to a developmental framework of Modes of Being and Learning that I created and elaborated with colleagues. I connect this picture with a number of related models, theories,…

  18. Facilitation skills for nurses

    Directory of Open Access Journals (Sweden)

    F Cilliers

    2000-09-01

    Full Text Available Using the pcrson-centered approach, facilitation in this study was conceptualised as providing opportunities for personal growth in the patient, and operationalised in a skills workshop for 40 nurses from different hospitals in Gauteng. The first objective was to evaluate the workshop and the second to ascertain its effect on the participant’s experienced performance. A combined quantitative and qualitative research design was used. The quantitative measurement (Personal Orientation Inventory, Carkhuff scales indicated that the workshop stimulated self-actualisation in terms of intrapersonal awareness, and the interpersonal skills of respect, realness, concreteness, empathy, as well as in terms of attending and responding behaviour. The qualitative measurement (a semi-structured interview indicated that the participants were able to empower patients to find their own answers to difficult personal questions. The alternative hypothesis was accepted, namely that this workshop in facilitations skills significantly enhanced the intra- and interpersonal characteristics associated with self-actualisation and the facilitation of growth in patients. The findings highlighted the difference between the two roles of instructor and facilitator, and recommendations to this effect were formulated.

  19. Facilitating leadership team communication

    OpenAIRE

    Hedman, Eerika

    2015-01-01

    The purpose of this study is to understand and describe how to facilitate competent communication in leadership teamwork. Grounded in the premises of social constructionism and informed by such theoretical frameworks as coordinated management of meaning theory (CMM), dialogic organization development (OD), systemic-constructionist leadership, communication competence, and reflexivity, this study seeks to produce further insights into understanding leadership team communicati...

  20. Stretchable silicon nanoribbon electronics for skin prosthesis.

    Science.gov (United States)

    Kim, Jaemin; Lee, Mincheol; Shim, Hyung Joon; Ghaffari, Roozbeh; Cho, Hye Rim; Son, Donghee; Jung, Yei Hwan; Soh, Min; Choi, Changsoon; Jung, Sungmook; Chu, Kon; Jeon, Daejong; Lee, Soon-Tae; Kim, Ji Hoon; Choi, Seung Hong; Hyeon, Taeghwan; Kim, Dae-Hyeong

    2014-12-09

    Sensory receptors in human skin transmit a wealth of tactile and thermal signals from external environments to the brain. Despite advances in our understanding of mechano- and thermosensation, replication of these unique sensory characteristics in artificial skin and prosthetics remains challenging. Recent efforts to develop smart prosthetics, which exploit rigid and/or semi-flexible pressure, strain and temperature sensors, provide promising routes for sensor-laden bionic systems, but with limited stretchability, detection range and spatio-temporal resolution. Here we demonstrate smart prosthetic skin instrumented with ultrathin, single crystalline silicon nanoribbon strain, pressure and temperature sensor arrays as well as associated humidity sensors, electroresistive heaters and stretchable multi-electrode arrays for nerve stimulation. This collection of stretchable sensors and actuators facilitate highly localized mechanical and thermal skin-like perception in response to external stimuli, thus providing unique opportunities for emerging classes of prostheses and peripheral nervous system interface technologies.

  1. Stretchable silicon nanoribbon electronics for skin prosthesis

    Science.gov (United States)

    Kim, Jaemin; Lee, Mincheol; Shim, Hyung Joon; Ghaffari, Roozbeh; Cho, Hye Rim; Son, Donghee; Jung, Yei Hwan; Soh, Min; Choi, Changsoon; Jung, Sungmook; Chu, Kon; Jeon, Daejong; Lee, Soon-Tae; Kim, Ji Hoon; Choi, Seung Hong; Hyeon, Taeghwan; Kim, Dae-Hyeong

    2014-12-01

    Sensory receptors in human skin transmit a wealth of tactile and thermal signals from external environments to the brain. Despite advances in our understanding of mechano- and thermosensation, replication of these unique sensory characteristics in artificial skin and prosthetics remains challenging. Recent efforts to develop smart prosthetics, which exploit rigid and/or semi-flexible pressure, strain and temperature sensors, provide promising routes for sensor-laden bionic systems, but with limited stretchability, detection range and spatio-temporal resolution. Here we demonstrate smart prosthetic skin instrumented with ultrathin, single crystalline silicon nanoribbon strain, pressure and temperature sensor arrays as well as associated humidity sensors, electroresistive heaters and stretchable multi-electrode arrays for nerve stimulation. This collection of stretchable sensors and actuators facilitate highly localized mechanical and thermal skin-like perception in response to external stimuli, thus providing unique opportunities for emerging classes of prostheses and peripheral nervous system interface technologies.

  2. Sphere impact and penetration into wet sand

    Science.gov (United States)

    Marston, J. O.; Vakarelski, I. U.; Thoroddsen, S. T.

    2012-08-01

    We present experimental results for the penetration of a solid sphere when released onto wet sand. We show, by measuring the final penetration depth, that the cohesion induced by the water can result in either a deeper or shallower penetration for a given release height compared to dry granular material. Thus the presence of water can either lubricate or stiffen the granular material. By assuming the shear rate is proportional to the impact velocity and using the depth-averaged stopping force in calculating the shear stress, we derive effective viscosities for the wet granular materials.

  3. Earthquakes induced by deep penetrating bombing?

    Institute of Scientific and Technical Information of China (English)

    Serguei Yu. Balassanian

    2005-01-01

    The data of M≥5 earthquakes occurred in one year before and after 4 deep penetrating bombs in the region within 500 km and 1 000 km from the shooting site are presented. The 4 bombs are those happened in 1999 Kosovo of Yugoslavia, the 1991 Baghdad of Iraq, the 2001 Tora Bora of Afghanistan, and the 2003 Kirkuk of Iraq, respectively. The data indicate that the deep penetrating bombs may have remotely triggered some earthquakes. The deep penetrating bombs in seismically active regions should be forbidden.

  4. Percutaneous penetration studies for risk assessment

    DEFF Research Database (Denmark)

    Sartorelli, Vittorio; Andersen, Helle Raun; Angerer, Jürgen

    2000-01-01

    . In order to predict the systemic risk of dermally absorbed chemicals and to enable agencies to set safety standards, data is needed on the rates of percutaneous penetration of important chemicals. Standardization of in vitro tests and comparison of their results with the in vivo data could produce...... of percutaneous penetration. This paper is an outcome of the meetings of the Percutaneous Penetration Subgroup and reports the presentations on the key issues identified throughout the 3-year duration of the Dermal Exposure Network (1997-1999)....

  5. Sphere impact and penetration into wet sand

    KAUST Repository

    Marston, J. O.

    2012-08-07

    We present experimental results for the penetration of a solid sphere when released onto wet sand. We show, by measuring the final penetration depth, that the cohesion induced by the water can result in either a deeper or shallower penetration for a given release height compared to dry granular material. Thus the presence of water can either lubricate or stiffen the granular material. By assuming the shear rate is proportional to the impact velocity and using the depth-averaged stopping force in calculating the shear stress, we derive effective viscosities for the wet granular materials.

  6. Simulated meteoroid penetration of reusable surface insulation

    Science.gov (United States)

    Lehman, J. K.; Christensen, H. E.

    1973-01-01

    Meteoroid impact simulation test results on insulation tiles were used to determine penetration resistance of reusable surface insulation attached to simulated shuttle structures. The probability of no meteoroid damage to a typical shuttle orbiter was determined. Specimens were plasma jet tested to determine effects of various size meteoroid cavities on their thermal performance. None of the tiles failed catastrophically, but large, egg-shaped craters did result from meteoroid penetration. The metallic side of a specimen that was completely penetrated showed a petalled hole typical for thin gage shielded structures.

  7. Transdermal drug delivery by in-skin electroporation using a microneedle array.

    Science.gov (United States)

    Yan, Keshu; Todo, Hiroaki; Sugibayashi, Kenji

    2010-09-15

    The aim of the present work was to develop a minimally invasive system for the delivery of macromolecular drugs to the deep skin tissues, so-called in-skin electroporation (IN-SKIN EP), using a microneedle (MN) electrode array. Fluorescein isothiocyanate (FITC)-dextran (FD-4: average molecular weight, 4.3 kDa) was used as the model macromolecular drug. MNs were arranged to puncture the skin barrier, the stratum corneum, and electrodes were used for EP so that a high electric field could be applied to skin tissues to promote viable skin delivery. In vitro skin permeation experiments showed that IN-SKIN EP had a much higher skin penetration-enhancing effect for FD-4 than MN alone or ON-SKIN EP (conventional EP treatment), and that higher permeation was achieved by applying a higher voltage and longer pulse width of EP. In addition, no marked skin irritation was observed by IN-SKIN EP, which was determined by the LDH leaching test. These results suggest that IN-SKIN EP can be more effectively utilized as a potential skin delivery system of macromolecular drugs than MN alone and conventional ON-SKIN EP.

  8. A Mass Loss Penetration Model to Investigate the Dynamic Response of a Projectile Penetrating Concrete considering Mass Abrasion

    OpenAIRE

    NianSong Zhang; Dong; Wang; Bei Peng; Yong He

    2015-01-01

    A study on the dynamic response of a projectile penetrating concrete is conducted. The evolutional process of projectile mass loss and the effect of mass loss on penetration resistance are investigated using theoretical methods. A projectile penetration model considering projectile mass loss is established in three stages, namely, cratering phase, mass loss penetration phase, and remainder rigid projectile penetration phase.

  9. Day-Ahead Energy Planning with 100% Electric Vehicle Penetration in the Nordic Region by 2050

    DEFF Research Database (Denmark)

    Liu, Zhaoxi; Wu, Qiuwei; Nielsen, Arne Hejde

    2014-01-01

    This paper presents the day-ahead energy planning of passenger cars with 100% electric vehicle (EV) penetration in the Nordic region by 2050. EVs will play an important role in the future energy systems which can both reduce the greenhouse gas (GHG) emission from the transport sector and provide...... demand side flexibility required by the smart grids. On the other hand, the EVs will increase the electricity consumption. In order to quantify the electricity consumption increase due to the 100% EV penetration in the Nordic region to facilitate the power system planning studies, the day-ahead energy...

  10. Investigation of cutaneous penetration properties of stearic acid loaded to dendritic core-multi-shell (CMS) nanocarriers.

    Science.gov (United States)

    Lohan, S B; Icken, N; Teutloff, C; Saeidpour, S; Bittl, R; Lademann, J; Fleige, E; Haag, R; Haag, S F; Meinke, M C

    2016-03-30

    Dendritic core-multi shell (CMS) particles are polymer based systems consisting of a dendritic polar polyglycerol polymer core surrounded by a two-layer shell of nonpolar C18 alkyl chains and hydrophilic polyethylene glycol. Belonging to nanotransport systems (NTS) they allow the transport and storage of molecules with different chemical characters. Their amphipihilic character CMS-NTS permits good solubility in aqueous and organic solutions. We showed by multifrequency electron paramagnetic resonance (EPR) spectroscopy that spin-labeled 5-doxyl stearic acid (5DSA) can be loaded into the CMS-NTS. Furthermore, the release of 5DSA from the carrier into the stratum corneum of porcine skin was monitored ex vivo by EPR spectroscopy. Additionally, the penetration of the CMS-NTS into the skin was analyzed by fluorescence microscopy using indocarbocyanine (ICC) covalently bound to the nanocarrier. Thereby, no transport into the viable skin was observed, whereas the CMS-NTS had penetrated into the hair follicles down to a depth of 340 μm ± 82 μm. Thus, it could be shown that the combined application of fluorescence microscopy and multi-frequency EPR spectroscopy can be an efficient tool for investigating the loading of spin labeled drugs to nanocarrier systems, drug release and penetration into the skin as well as the localization of the NTS in the skin. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. In vitro dermal penetration of nickel nanoparticles.

    Science.gov (United States)

    Crosera, Matteo; Adami, Gianpiero; Mauro, Marcella; Bovenzi, Massimo; Baracchini, Elena; Larese Filon, Francesca

    2016-02-01

    Nickel nanoparticles (NiNPs) represent a new type of occupational exposure because, due to the small size/high surface, they can release more Ni ions compared to bulk material. It has been reported a case of a worker who developed sensitization while handling nickel nanopowder without precautions. Therefore there is the need to assess whether the skin absorption of NiNPs is higher compared to bulk nickel. Two independent in vitro experiments were performed using Franz diffusion cells. Eight cells for each experiment were fitted using intact and needle-abraded human skin. The donor phase was a suspension of NiNPs with mean size of 77.7 ± 24.1 nm in synthetic sweat. Ni permeated both types of skin, reaching higher levels up to two orders of magnitude in the damaged skin compared to intact skin (5.2 ± 2.0 vs 0.032 ± 0.010 μg cm(-2), p = 0.006) at 24 h. Total Ni amount into the skin was 29.2 ± 11.2 μg cm(-2) in damaged skin and 9.67 ± 2.70 μg cm(-2) in intact skin (mean and SD, p = 0.006). Skin abrasions lead to doubling the Ni amount in the epidermis and to an increase of ten times in the dermis. This study demonstrated that NiNPs applied on skin surface cause an increase of nickel content into the skin and a significant permeation flux through the skin, higher when a damaged skin protocol was used. Preventive measures are needed when NiNPs are produced and used due to their higher potential to enter in our body compared to bulk nickel.

  12. Comparison of protocols for measuring cosmetic ingredient distribution in human and pig skin.

    Science.gov (United States)

    Gerstel, D; Jacques-Jamin, C; Schepky, A; Cubberley, R; Eilstein, J; Grégoire, S; Hewitt, N; Klaric, M; Rothe, H; Duplan, H

    2016-08-01

    The Cosmetics Europe Skin Bioavailability and Metabolism Task Force aims to improve the measurement and prediction of the bioavailability of topically-exposed compounds for risk assessment. Key parameters of the experimental design of the skin penetration studies were compared. Penetration studies with frozen human and pig skin were conducted in two laboratories, according to the SCCS and OECD 428 guidelines. The disposition in skin was measured 24h after finite topical doses of caffeine, resorcinol and 7-ethoxycoumarin. The bioavailability distribution in skin layers of cold and radiolabelled chemicals were comparable. Furthermore, the distribution of each chemical was comparable in human and pig skin. The protocol was reproducible across the two laboratories. There were small differences in the amount of chemical detected in the skin layers, which were attributed to differences in washing procedures and anatomical sites of the skin used. In conclusion, these studies support the use of pig skin as an alternative source of skin should the availability of human skin become a limiting factor. If radiolabelled chemicals are not available, cold chemicals can be used, provided that the influence of chemical stability, reactivity or metabolism on the experimental design and the relevance of the data obtained is considered.

  13. [Sarcoidosis of the skin].

    Science.gov (United States)

    Suga, Y; Ogawa, H

    1994-06-01

    Sarcoidosis is characterized by formation of epithelioid-cell tubercules, without caseation, of the affected organ systems. The mediastinum, peripheral lymph nodes and eyes, in addition to the skin, are most frequently affected. Between 10% and 30% of patients with systemic sarcoidosis in Japan have skin lesions. Skin sarcoidosis is morphologically classified into three basic groups, erythema nodosum, scar sarcoidosis and skin sarcoid. Skin sarcoid is characterized by specific cutaneous lesions of sarcoidosis, and may take nodular, plaque, angiolupoid, subcutaneous and some other forms. Clinical manifestations of the cutaneous lesions are usually asymptomatic and polymorphous. Skin biopsy is, however, often highly useful for confirming a diagnosis of sarcoidosis.

  14. Biaxial mechanical characterization of bat wing skin.

    Science.gov (United States)

    Skulborstad, A J; Swartz, S M; Goulbourne, N C

    2015-04-21

    The highly flexible and stretchable wing skin of bats, together with the skeletal structure and musculature, enables large changes in wing shape during flight. Such compliance distinguishes bat wings from those of all other flying animals. Although several studies have investigated the aerodynamics and kinematics of bats, few have examined the complex histology and mechanical response of the wing skin. This work presents the first biaxial characterization of the local deformation, mechanical properties, and fiber kinematics of bat wing skin. Analysis of these data has provided insight into the relationships among the structural morphology, mechanical properties, and functionality of wing skin. Large spatial variations in tissue deformation and non-negligible fiber strains in the cross-fiber direction for both chordwise and spanwise fibers indicate fibers should be modeled as two-dimensional elements. The macroscopic constitutive behavior was anisotropic and nonlinear, with very low spanwise and chordwise stiffness (hundreds of kilopascals) in the toe region of the stress-strain curve. The structural arrangement of the fibers and matrix facilitates a low energy mechanism for wing deployment and extension, and we fabricate examples of skins capturing this mechanism. We propose a comprehensive deformation map for the entire loading regime. The results of this work underscore the importance of biaxial field approaches for soft heterogeneous tissue, and provide a foundation for development of bio-inspired skins to probe the effects of the wing skin properties on aerodynamic performance.

  15. 3D Ground Penetrating Imaging Radar

    OpenAIRE

    ECT Team, Purdue

    2007-01-01

    GPiR (ground-penetrating imaging radar) is a new technology for mapping the shallow subsurface, including society’s underground infrastructure. Applications for this technology include efficient and precise mapping of buried utilities on a large scale.

  16. Penetration testing protecting networks and systems

    CERN Document Server

    Henry, Kevin M

    2012-01-01

    This book is a preparation guide for the CPTE examination, yet is also a general reference for experienced penetration testers, ethical hackers, auditors, security personnel and anyone else involved in the security of an organization's computer systems.

  17. Identifying structural damage with ground penetrating radar

    CSIR Research Space (South Africa)

    Van Schoor, Abraham M

    2008-07-01

    Full Text Available Ground penetrating radar (GPR) and electrical resistance tomography (ERT) surveys were conducted in an urban environment in an attempt to identify the cause of severe structural damage to a historically significant residential property...

  18. Kali Linux wireless penetration testing beginner's guide

    CERN Document Server

    Ramachandran, Vivek

    2015-01-01

    If you are a security professional, pentester, or anyone interested in getting to grips with wireless penetration testing, this is the book for you. Some familiarity with Kali Linux and wireless concepts is beneficial.

  19. Airborne ground penetrating radar: practical field experiments

    CSIR Research Space (South Africa)

    Van Schoor, Michael

    2013-10-01

    Full Text Available The performance of ground penetrating radar (GPR) under conditions where the ground coupling of the antenna is potentially compromised is investigated. Of particular interest is the effect of increasing the distance between the antennae...

  20. An Observational Investigation of Penetrative Convection

    DEFF Research Database (Denmark)

    Jensen, Niels Otto; Lenschow, D. H.

    1978-01-01

    Data taken during the Air Mass Transformation Experiment (AMTEX) by the NCAR Electra aircraft have proven useful for investigating the structure of thermals penetrating into the turbulent inversion layer which caps the convective mixed layer. Variances, covariances, spectra and cospectra...

  1. Prediction of weld penetration extent in GTAW

    Institute of Scientific and Technical Information of China (English)

    Zhao Ming; Zhai Lei

    2008-01-01

    The governing equations of surface-deformation in fully-penetrated GTA W weld pool are derived. The solution scheme of the Lagrange multiplier, which makes the top sutface-deformation equation be coupled with that for the bottomsurface of a single weld pool, is given out. Through numerical analysis of weld pool surface-deformation in GTA W,it is found that there is clear correlation between the penetration extent and the Lagrange multiplier, in addition to the relationship between the penetration extent and the maximum depression and hump as well as the depressed volume of the top surface of weld pool. It lays good foundation for top-side sensing based weld penetration control.

  2. Penetrating facial injury by a wooden log

    OpenAIRE

    Mohan, Sadanandan; Varghese, George; Kumar, Sanjay; Subramanian, Dinesh Pambungal

    2014-01-01

    Penetrating facial injuries are potentially dangerous and require emergency management because of the presence of vital structures in the face and it may be life threatening especially when the injury involves airway, major blood vessels, spinal cord and cervical spines. Penetrating injuries of facial region can occur due to missile injuries, blast injuries, accidental fall on sharp objects such as sticks or glass and motor vehicle accidents etc., Indications for immediate surgical management...

  3. Magnetic field penetration of erosion switch plasmas

    Science.gov (United States)

    Mason, Rodney J.; Jones, Michael E.; Grossmann, John M.; Ottinger, Paul F.

    1988-10-01

    Computer simulations demonstrate that the entrainment (or advection) of magnetic field with the flow of cathode-emitted electrons can constitute a dominant mechanism for the magnetic field penetration of erosion switch plasmas. Cross-field drift in the accelerating electric field near the cathode starts the penetration process. Plasma erosion propagates the point for emission and magnetic field injection along the cathode toward the load-for the possibility of rapid switch opening.

  4. Effect of penetrants on the aramid Nomex

    Indian Academy of Sciences (India)

    Anjana Jain; Kalyani Vijayan

    2000-06-01

    The response of Nomex sheets to some penetrants has been analyzed. The process of moisture uptake depends on the relative humidity (RH) of the ambient atmosphere and the initial characteristics of the polymer. In the case of common laboratory solvents, the uptake by the polymer shows an inverse dependence on the molar volume of the former. Although the calendered and the uncalendered Nomex sheets exhibit an overall similarity in their response to various penetrants, quantitative comparison reveals distinct differences.

  5. Mindfulness for group facilitation

    DEFF Research Database (Denmark)

    Adriansen, Hanne Kirstine; Krohn, Simon

    2014-01-01

    In this paper, we argue that mindfulness techniques can be used for enhancing the outcome of group performance. The word mindfulness has different connotations in the academic literature. Broadly speaking there is ‘mindfulness without meditation’ or ‘Western’ mindfulness which involves active...... thinking and ‘Eastern’ mindfulness which refers to an open, accepting state of mind, as intended with Buddhist-inspired techniques such as meditation. In this paper, we are interested in the latter type of mindfulness and demonstrate how Eastern mindfulness techniques can be used as a tool for facilitation....... A brief introduction to the physiology and philosophy of Eastern mindfulness constitutes the basis for the arguments of the effect of mindfulness techniques. The use of mindfulness techniques for group facilitation is novel as it changes the focus from individuals’ mindfulness practice...

  6. Facilitating Learning at Conferences

    DEFF Research Database (Denmark)

    Ravn, Ib; Elsborg, Steen

    2011-01-01

    and facilitate a variety of simple learning techniques at thirty one- and two-day conferences of up to 300 participants each. We present ten of these techniques and data evaluating them. We conclude that if conference organizers allocate a fraction of the total conference time to facilitated processes......The typical conference consists of a series of PowerPoint presentations that tend to render participants passive. Students of learning have long abandoned the transfer model that underlies such one-way communication. We propose an al-ternative theory of conferences that sees them as a forum...... for learning, mutual inspiration and human flourishing. We offer five design principles that specify how conferences may engage participants more and hence increase their learning. In the research-and-development effort reported here, our team collaborated with conference organizers in Denmark to introduce...

  7. Stress relaxation analysis facilitates a quantitative approach towards antimicrobial penetration into biofilms

    NARCIS (Netherlands)

    He, Yan; Peterson, Brandon W; Jongsma, Marije A; Ren, Yijin; Sharma, Prashant K; Busscher, Henk J; van der Mei, Henny C

    2013-01-01

    Biofilm-related infections can develop everywhere in the human body and are rarely cleared by the host immune system. Moreover, biofilms are often tolerant to antimicrobials, due to a combination of inherent properties of bacteria in their adhering, biofilm mode of growth and poor physical penetrati

  8. Photoinduced disaggregation of TiO₂ nanoparticles enables transdermal penetration.

    Directory of Open Access Journals (Sweden)

    Samuel W Bennett

    Full Text Available Under many aqueous conditions, metal oxide nanoparticles attract other nanoparticles and grow into fractal aggregates as the result of a balance between electrostatic and Van Der Waals interactions. Although particle coagulation has been studied for over a century, the effect of light on the state of aggregation is not well understood. Since nanoparticle mobility and toxicity have been shown to be a function of aggregate size, and generally increase as size decreases, photo-induced disaggregation may have significant effects. We show that ambient light and other light sources can partially disaggregate nanoparticles from the aggregates and increase the dermal transport of nanoparticles, such that small nanoparticle clusters can readily diffuse into and through the dermal profile, likely via the interstitial spaces. The discovery of photoinduced disaggregation presents a new phenomenon that has not been previously reported or considered in coagulation theory or transdermal toxicological paradigms. Our results show that after just a few minutes of light, the hydrodynamic diameter of TiO(2 aggregates is reduced from ∼280 nm to ∼230 nm. We exposed pigskin to the nanoparticle suspension and found 200 mg kg(-1 of TiO(2 for skin that was exposed to nanoparticles in the presence of natural sunlight and only 75 mg kg(-1 for skin exposed to dark conditions, indicating the influence of light on NP penetration. These results suggest that photoinduced disaggregation may have important health implications.

  9. Percutaneous penetration of methyl nicotinate from ointments using the laser Doppler technique: bioequivalence and enhancer effects.

    Science.gov (United States)

    Remane, Yvonne; Leopold, Claudia S; Maibach, Howard I

    2006-12-01

    Laser Doppler flowmetry (LDF) may be used to quantify erythema response as a result of an increased cutaneous microcirculation induced by methyl nicotinate (MN). Bioequivalence of a test and a standard preparation (vehicles: light mineral oil and medium chain triglycerides, respectively) was confirmed according to the pilot study of the FDA Guidance for Industry "Topical dermatologic corticosteroids: In Vivo bioequivalence" applying the staggered application and synchronized removal method for one defined concentration. Furthermore, the influence of penetration enhancers (5% w/w Dimethylsulfoxide (DMSO) and 10% w/w diethylene glycol monoethyl ether) on MN penetration was investigated. It was shown that DMSO and diethylene glycol monoethyl ether altered cutaneous microcirculation and thus MN penetration in comparison to the standard formulation. However, true penetration enhancement could only be proved with diethylene glycol monoethyl ether resulting from an improved drug solubility in the skin which was confirmed by attenuated total reflectance fourier transform infrared spectroscopy (ATR-FTIR). Increased MN penetration by DMSO was only caused by thermodynamic effects, i.e. a decreased drug solubility in the vehicle.

  10. Program Facilitates Distributed Computing

    Science.gov (United States)

    Hui, Joseph

    1993-01-01

    KNET computer program facilitates distribution of computing between UNIX-compatible local host computer and remote host computer, which may or may not be UNIX-compatible. Capable of automatic remote log-in. User communicates interactively with remote host computer. Data output from remote host computer directed to local screen, to local file, and/or to local process. Conversely, data input from keyboard, local file, or local process directed to remote host computer. Written in ANSI standard C language.

  11. Facilitating Knowledge Sharing

    OpenAIRE

    Holdt Christensen, Peter

    2005-01-01

    Abstract This paper argues that knowledge sharing can be conceptualized as different situations of exchange in which individuals relate to each other in different ways, involving different rules, norms and traditions of reciprocity regulating the exchange. The main challenge for facilitating knowledge sharing is to ensure that the exchange is seen as equitable for the parties involved, and by viewing the problems of knowledge sharing as motivational problems situated in different organization...

  12. Penetration of Bdellovibrio bacteriovorus into host cells.

    Science.gov (United States)

    Abram, D; Castro e Melo, J; Chou, D

    1974-05-01

    Electron microscopy reveals that, in Bdellovibrio infection, after the formation of a passage pore in the host cell wall, the differentiated parasite penetration pole is associated with the host protoplast. This firm contact persists throughout the parasite penetration and after this process is completed. In penetrated hosts this contact is also apparent by phase microscopy. The association between the walls of the parasite and the host at the passage pore, on the other hand, is transient. Bdellovibrio do not penetrate hosts whose protoplast and cell walls are separated by plasmolysis, or in which the membrane-wall relationship is affected by low turgor pressure. It is concluded, therefore, that for penetration to occur it is essential that the host protoplast be within reach of the parasite, so that a firm contact can be established between them. A penetration mechanism is proposed that is effected by forces generated by fluxes of water and solutes due to structural changes in the infected host envelope. These forces cause a differential expansion of the host protoplast and cell wall and their separation from each other around the entry site, while the parasite remains firmly anchored to the host protoplast. Consequently, the parasite ends up enclosed in the expanded host periplasm. The actual entry, therefore, is a passive act of the parasite.

  13. Estimating Consequences of MMOD Penetrations on ISS

    Science.gov (United States)

    Evans, H.; Hyde, James; Christiansen, E.; Lear, D.

    2017-01-01

    The threat from micrometeoroid and orbital debris (MMOD) impacts on space vehicles is often quantified in terms of the probability of no penetration (PNP). However, for large spacecraft, especially those with multiple compartments, a penetration may have a number of possible outcomes. The extent of the damage (diameter of hole, crack length or penetration depth), the location of the damage relative to critical equipment or crew, crew response, and even the time of day of the penetration are among the many factors that can affect the outcome. For the International Space Station (ISS), a Monte-Carlo style software code called Manned Spacecraft Crew Survivability (MSCSurv) is used to predict the probability of several outcomes of an MMOD penetration-broadly classified as loss of crew (LOC), crew evacuation (Evac), loss of escape vehicle (LEV), and nominal end of mission (NEOM). By generating large numbers of MMOD impacts (typically in the billions) and tracking the consequences, MSCSurv allows for the inclusion of a large number of parameters and models as well as enabling the consideration of uncertainties in the models and parameters. MSCSurv builds upon the results from NASA's Bumper software (which provides the probability of penetration and critical input data to MSCSurv) to allow analysts to estimate the probability of LOC, Evac, LEV, and NEOM. This paper briefly describes the overall methodology used by NASA to quantify LOC, Evac, LEV, and NEOM with particular emphasis on describing in broad terms how MSCSurv works and its capabilities and most significant models.

  14. Giant gastric ulcer penetrating into the pancreas.

    Science.gov (United States)

    Fujihara, Shintaro; Mori, Hirohito; Nishiyama, Noriko; Kobara, Hideki; Masaki, Tsutomu

    2012-09-01

    A 57-year-old man developed haematemesis and was referred to our institution. His discomfort had begun 3 weeks earlier and localised to the upper abdomen. Abdominal CT showed a defect of gastric mucosa and gastric wall thickening. Oesophagogastroduodenoscopy showed that he had an active gastric ulcer, 40 mm in diameter, on the lesser curvature in the upper third of the corpus and the presence of a pancreatic body at the ulcer base, penetration to the pancreas. Open gastrectomy was performed with a preoperative diagnosis of localised peritonitis caused by penetration of the stomach into the pancreas. Histopathology of resected specimens showed a benign peptic ulcer, 40×40 mm in size, was found on the lesser curvature in the antrum, and this had penetrated through the pancreas. The most serious complications of PUD include haemorrhage, perforation, penetration, and gastric outlet obstruction. Approximately 7% of patients experience perforation, which occurs when an ulcer erodes through the wall and leaks air and digestive contents into the peritoneal cavity. Antral and duodenal ulcers can penetrate into the pancreas. We report a case of gastric ulcer penetrating into the pancreas.

  15. Simulation of Mine Electrical Penetration Technology

    Institute of Scientific and Technical Information of China (English)

    LIU Zhi-xin; YUE Jian-hua; LIU Shu-cai

    2007-01-01

    Based on the principle of electrical penetration, the reflection characteristics of collapse columns at different locations of a working face is numerically simulated by using a 3D finite element method. The data collected by the electrical penetration is processed and interpreted using "tunnel penetration" which is similar to radio wave penetration. Reflection characteristics of collapse columns at different locations below floors of coal seams are analyzed, providing a new paradigm and a theoretical foundation for processing and interpreting electrical penetration data. The tomography analysis is made based on data simulation and calculation results and alltransmitting-receiving points are analyzed for their corresponding maximum attenuation values and maximum absorption coefficients. On the basis of this, a new method for precisely interpreting the spatial positions of geological anomalous bodies is suggested. The simulation shows that 1) the detection result of both roof and floors of the working face by electrical penetration is a volumetric effect and 2) there exists a corresponding relation between the detection depth and the working face width, with the optimal detection depth within 40% of the working face width.

  16. Skin Stem Cells in Skin Cell Therapy

    Directory of Open Access Journals (Sweden)

    Mollapour Sisakht

    2015-12-01

    Full Text Available Context Preclinical and clinical research has shown that stem cell therapy is a promising therapeutic option for many diseases. This article describes skin stem cells sources and their therapeutic applications. Evidence Acquisition Compared with conventional methods, cell therapy reduces the surgical burden for patients because it is simple and less time-consuming. Skin cell therapy has been developed for variety of diseases. By isolation of the skin stem cell from the niche, in vitro expansion and transplantation of cells offers a surprising healing capacity profile. Results Stem cells located in skin cells have shown interesting properties such as plasticity, transdifferentiation, and specificity. Mesenchymal cells of the dermis, hypodermis, and other sources are currently being investigated to promote regeneration. Conclusions Because skin stem cells are highly accessible from autologous sources and their immunological profile is unique, they are ideal for therapeutic approaches. Optimization of administrative routes requires more investigation own to the lack of a standard protocol.

  17. In vitro penetration of bleaching agents into the pulp chamber

    DEFF Research Database (Denmark)

    Benetti, Ana Raquel; Valera, M C; Mancini, M N G

    2004-01-01

    To investigate pulp chamber penetration of bleaching agents in teeth following restorative procedures.......To investigate pulp chamber penetration of bleaching agents in teeth following restorative procedures....

  18. Eyebrow Reconstruction Using a Composite Skin Graft from Sideburns

    Directory of Open Access Journals (Sweden)

    Ken Matsuda, MD, PhD

    2015-01-01

    Full Text Available Summary: Wide resection of malignant skin tumors in the upper orbital region often results in soft-tissue defects involving the eyebrow. We used composite skin grafts from the area around the sideburns for 1-stage reconstruction of skin and eyebrow defects. The results were aesthetically satisfying because the hair and shape of these regions were similar to those of the original eyebrow, and donor-site closure was easy with inconspicuous scar. The survival of full-thickness skin graft area of composite grafts from sideburn facilitates revascularization of thicker hair follicles in the graft and allows safe, natural eyebrow reconstruction.

  19. Skin permeation of lidocaine from crystal suspended oily formulations.

    Science.gov (United States)

    Matsui, Rakan; Hasegawa, Masaaki; Ishida, Masami; Ebata, Toshiya; Namiki, Noriyuki; Sugibayashi, Kenji

    2005-09-01

    In vitro permeation of lidocaine (lidocaine base, LID) through excised rat skin was investigated using several LID-suspended oily formulations. The first skin permeation of LID from an LID-suspended oily solution such as liquid paraffin (LP), isopropyl myristate (IPM), polyoxyethylene (2) oleylether (BO-2), and diethyl sebacate (DES) was evaluated and compared with that from polyethylene glycol 400 (PEG400) solution, a hydrophilic base. The obtained permeation rate of LID, Japp, from PEG400, LP, IPM, BO-2, and DES was in the order of DES>BO-2=IPM>LP>PEG400, and increased with LID solubility in the oily solvents, although LID crystals were dispersed in all solvents. Subsequently, oily formulations that consisted of different ratios of the first oily solvent (IPM, BO-2, or DES) (each 0-20%), the second oily solvent (LP) and an oily mixture of microcrystalline wax/white petrolatum/paraffin (1/5/4) were evaluated. BO-2 groups at a concentration of 5% and 10% had the highest Japp among the oily formulations, although a higher BO-2 resulted in lower skin permeation. In addition, pretreatment with BO-2 increased the skin permeation of LID. These results suggest that the penetration enhancing effect by the system may be related to the skin penetration of BO-2 itself. Finally, mathematical analysis was done to evaluate the effect of BO-2, and it was shown that BO-2 improved the LID solubility in stratum corneum lipids to efficiently enhance the LID permeation through skin.

  20. Percutaneous penetration characteristics and release kinetics of contact allergens encapsulated in ethosomes.

    Science.gov (United States)

    Madsen, Jakob Torp; Vogel, Stefan; Johansen, Jeanne Duus; Sørensen, Jens Ahm; Andersen, Klaus Ejner; Nielsen, Jesper Bo

    2011-03-01

    Formulation of the contact allergens dinitrochlorobenzene and isoeugenol in ethanolic liposomes (ethosomes) increases their sensitizing properties in the local lymph node assay compared with an ethanol-water formulation of the allergens. Likewise, isoeugenol and methyldibromo-glutaronitrile formulated in ethosomes enhanced the patch test reactions in sensitized human volunteers. The relationship between the percutaneous penetration/absorption and sensitization/elicitation phases of contact allergy is not well elucidated. The aim of this study was to investigate whether the observed increased sensitizing and elicitation properties following the formulation of selected contact allergens in ethosomes could be explained by a change in release kinetics of the allergens and their pattern of percutaneous penetration and absorption as well as allergen deposition in epidermis and dermis. Release kinetics were studied using dialysis bags, and samples were taken at selected time points until equilibrium was reached. Percutaneous absorption and penetration were studied using human skin on Franz cells, and receptor fluid samples were taken at selected time points. Experiments were terminated after 24 hours, and deposition of allergen in epidermis and dermis was measured. Maximum flux and lag time were calculated. Ethosome formulation decreased the release of both allergens compared with the ethanol-water formulation. Ethosome formulation of dinitrochlorobenzene increased its percutaneous penetration but reduced the percutaneous penetration of isoeugenol compared with control formulations. Likewise, all other calculated parameters showed an opposite trend for the 2 allergens in ethosomes and ethanol-water. The present study demonstrates that identical ethosomes affect the percutaneous penetration characteristics of 2 allergens differently. Thus, our results indicate that each combination of an allergen and a vehicle needs to be evaluated separately. The exact mechanistic

  1. Dermal penetration of [14C]captan in young and adult rats.

    Science.gov (United States)

    Fisher, H L; Hall, L L; Sumler, M R; Shah, P V

    1992-07-01

    Age dependence in dermal absorption has been a major concern in risk assessment. Captan, a chloroalkyl thio heterocyclic fungicide, was selected for study of age dependence as representative of this class of pesticides. Dermal penetration of [14C]captan applied at 0.286 mumol/cm2 was determined in young (33-d-old) and adult (82-d-old) female Fischer 344 rats in vivo and by two in vitro methods. Dermal penetration in vivo at 72 h was about 9% of the recovered dose in both young and adult rats. The percentage penetration was found to increase as dosage (0.1, 0.5, 2.7 mumol/cm2) decreased. Two in vitro methods gave variable dermal penetration values compared with in vivo results. A static system yielded twofold higher dermal penetration values compared with in vivo results for both young and adult rats. A flow system yielded higher dermal penetration values in young rats and lower penetration values in adults compared with in vivo results. Concentration in body, kidney, and liver was less in young than in adult rats given the same absorbed dosage. A physiological pharmacokinetic model was developed having a dual compartment for the treated skin and appeared to describe dermal absorption and disposition well. From this model, tissue/blood ratios of captan-derived radioactivity for organs were found to range from 0.35 to 3.4, indicating no large uptake or binding preferences by any organ. This preliminary pharmacokinetic model summarizes the experimental findings and could provide impetus for more complex and realistic models.

  2. Learning about Skin Cancer

    Science.gov (United States)

    ... information, in skin cells, creating "misspellings" in their genetic code and, as a result, alter the function of those cells. Cancers generally are caused by a combination of environmental and genetic factors. With skin cancer, the environment plays a ...

  3. Examine Your Skin

    Medline Plus

    Full Text Available ... Items Awareness Store In Memory Melanoma Info Melanoma Facts Melanoma Prevention Sunscreen Suggestions Examine Your Skin Newly ... use this video. UPDATED: November 23, 2016 Melanoma Facts Melanoma Prevention Sunscreen Suggestions Examine Your Skin Newly ...

  4. Examine Your Skin

    Medline Plus

    Full Text Available ... Support Donate Share Facebook Twitter Newsletter Examine Your Skin Watch the video below and in only two minutes, you can learn to examine your skin. A special thanks to Dr. Martin Weinstock, MD, ...

  5. Examine Your Skin

    Medline Plus

    Full Text Available ... Support Donate Share Facebook Twitter Newsletter Examine Your Skin Watch the video below and in only two minutes, you can learn to examine your skin. A special thanks to Dr. Martin Weinstock, MD, ...

  6. Bleeding into the skin

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003235.htm Bleeding into the skin To use the sharing features on this page, please enable JavaScript. Bleeding into the skin can occur from broken blood ...

  7. Examine Your Skin

    Medline Plus

    Full Text Available ... Store In Memory Melanoma Info Melanoma Facts Melanoma Prevention Sunscreen Suggestions Examine Your Skin Newly Diagnosed? Understanding ... video. UPDATED: November 23, 2016 Melanoma Facts Melanoma Prevention Sunscreen Suggestions Examine Your Skin Newly Diagnosed? Understanding ...

  8. Examine Your Skin

    Medline Plus

    Full Text Available ... Store In Memory Melanoma Info Melanoma Facts Melanoma Prevention Sunscreen Suggestions Examine Your Skin Newly Diagnosed? Understanding ... video. UPDATED: November 23, 2016 Melanoma Facts Melanoma Prevention Sunscreen Suggestions Examine Your Skin Newly Diagnosed? Understanding ...

  9. Rapid penetration into granular media visualizing the fundamental physics of rapid earth penetration

    CERN Document Server

    Iskander, Magued

    2015-01-01

    Rapid Penetration into Granular Media: Visualizing the Fundamental Physics of Rapid Earth Penetration introduces readers to the variety of methods and techniques used to visualize, observe, and model the rapid penetration of natural and man-made projectiles into earth materials. It provides seasoned practitioners with a standard reference that showcases the topic's most recent developments in research and application. The text compiles the findings of new research developments on the subject, outlines the fundamental physics of rapid penetration into granular media, and assembles a com

  10. Discovery and characterization of a new cell-penetrating protein.

    Science.gov (United States)

    Simeon, Rudo L; Chamoun, Ana Maria; McMillin, Thomas; Chen, Zhilei

    2013-12-20

    We describe a new cell-penetrating protein, B1, capable of delivering conjugated proteins and nucleic acids into mammalian cells. B1 is a 244-amino-acid product of a single-base frameshift in the gene encoding enhanced green fluorescent protein (eGFP). The molecule has a net positive charge of 43 and a very high charge-to-mass ratio of 1.5. eGFP-fused B1 potently penetrates both adherent and suspension cells with >80% of cells taking up the protein when exposed to concentrations as low as 1 μM. The protein was found to cluster in the paranuclear region of TZM-bl cells. Most importantly, we show that B1 not only facilitates cellular uptake but allows biomolecular cargo to reach sites of biological relevance. For example, baby hamster kidney cells underwent DNA recombination when exposed to B1-tagged Cre recombinase at protein concentrations as low as 2.5 μM, indicating potent nuclear delivery of functional protein cargos. Additionally, B1 delivers noncovalently conjugated RNA and DNA across the cell membrane to cytosolic and nuclear sites accessible to the cellular translation and transcription machinery, as gauged by detection of encoded reporter functions, with efficiency comparable to commercially available cationic lipid reagents. B1 appears to utilize cell-surface glycans and multiple competing endocytic pathways to enter and traffic through cells. These studies provide both a new tool for intracellular delivery of biomolecules and insights that could aid in the design of more effective cell penetrating proteins.

  11. Ultrasound skin imaging.

    Science.gov (United States)

    Alfageme Roldán, F

    2014-12-01

    The interaction of high-frequency ultrasound waves with the skin provides the basis for noninvasive, fast, and accessible diagnostic imaging. This tool is increasingly used in skin cancer and inflammatory conditions as well as in cosmetic dermatology. This article reviews the basic principles of skin ultrasound and its applications in the different areas of dermatology.

  12. Skin self-exam

    Science.gov (United States)

    Skin cancer - self-exam; Melanoma - self-exam; Basal cell cancer - self-exam; Squamous cell - self-exam; Skin mole - self-exam ... Experts do not agree on whether or not skin self-exams should be performed. So there is ...

  13. Microbiome and skin diseases

    NARCIS (Netherlands)

    Zeeuwen, P.L.J.M.; Kleerebezem, M.; Timmerman, H.M.; Schalkwijk, J.

    2013-01-01

    PURPOSE OF REVIEW: This article reviews recent findings on the skin microbiome. It provides an update on the current understanding of the role of microbiota in healthy skin and in inflammatory and allergic skin diseases. RECENT FINDINGS: Advances in computing and high-throughput sequencing technolog

  14. Microbiome and skin diseases

    NARCIS (Netherlands)

    Zeeuwen, P.L.; Kleerebezem, M.; Timmerman, H.M.; Schalkwijk, J.

    2013-01-01

    Purpose of review: This article reviews recent findings on the skin microbiome. It provides an update on the current understanding of the role of microbiota in healthy skin and in inflammatory and allergic skin diseases. Recent findings: Advances in computing and high-throughput sequencing technolog

  15. Microbiome and skin diseases

    NARCIS (Netherlands)

    Zeeuwen, P.L.J.M.; Kleerebezem, M.; Timmerman, H.M.; Schalkwijk, J.

    2013-01-01

    PURPOSE OF REVIEW: This article reviews recent findings on the skin microbiome. It provides an update on the current understanding of the role of microbiota in healthy skin and in inflammatory and allergic skin diseases. RECENT FINDINGS: Advances in computing and high-throughput sequencing

  16. Microbiome and skin diseases

    NARCIS (Netherlands)

    Zeeuwen, P.L.; Kleerebezem, M.; Timmerman, H.M.; Schalkwijk, J.

    2013-01-01

    Purpose of review: This article reviews recent findings on the skin microbiome. It provides an update on the current understanding of the role of microbiota in healthy skin and in inflammatory and allergic skin diseases. Recent findings: Advances in computing and high-throughput sequencing

  17. On skin expansion.

    Science.gov (United States)

    Pamplona, Djenane C; Velloso, Raquel Q; Radwanski, Henrique N

    2014-01-01

    This article discusses skin expansion without considering cellular growth of the skin. An in vivo analysis was carried out that involved expansion at three different sites on one patient, allowing for the observation of the relaxation process. Those measurements were used to characterize the human skin of the thorax during the surgical process of skin expansion. A comparison between the in vivo results and the numerical finite elements model of the expansion was used to identify the material elastic parameters of the skin of the thorax of that patient. Delfino's constitutive equation was chosen to model the in vivo results. The skin is considered to be an isotropic, homogeneous, hyperelastic, and incompressible membrane. When the skin is extended, such as with expanders, the collagen fibers are also extended and cause stiffening in the skin, which results in increasing resistance to expansion or further stretching. We observed this phenomenon as an increase in the parameters as subsequent expansions continued. The number and shape of the skin expanders used in expansions were also studied, both mathematically and experimentally. The choice of the site where the expansion should be performed is discussed to enlighten problems that can lead to frustrated skin expansions. These results are very encouraging and provide insight into our understanding of the behavior of stretched skin by expansion. To our knowledge, this study has provided results that considerably improve our understanding of the behavior of human skin under expansion.

  18. PPD skin test

    Science.gov (United States)

    ... test; Mantoux test Images Tuberculosis in the kidney Tuberculosis in the lung Positive PPD skin test PPD skin test References Chernecky CC, Berger ... test, purified protein derivative test, Tb test, tuberculin skin test, TST, tuberculosis test) - diagnostic. In: Chernecky CC, Berger BJ, eds. ...

  19. Psychoneuroimmunology and the Skin.

    Science.gov (United States)

    Honeyman, Juan F

    2016-08-23

    The nervous, immune, endocrine and integumentary systems are closely related and interact in a number of normal and pathological conditions. Nervous system mediators may bring about direct changes to the skin or may induce the release of immunological or hormonal mediators that cause pathological changes to the skin. This article reviews the psychological mechanisms involved in the development of skin diseases.

  20. Facilitative root interactions in intercrops

    DEFF Research Database (Denmark)

    Hauggaard-Nielsen, H.; Jensen, E.S.

    2005-01-01

    Facilitation takes place when plants ameliorate the environment of their neighbours, and increase their growth and survival. Facilitation occurs in natural ecosystems as well as in agroecosystems. We discuss examples of facilitative root interactions in intercropped agroecosystems; including...... intensified cropping systems using chemical and mechanical inputs also show that facilitative interactions definitely can be of significance. It is concluded that a better understanding of the mechanisms behind facilitative interactions may allow us to benefit more from these phenomena in agriculture...