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Skin Penetration (skin + penetration)
Selected AbstractsAn in vivo model to evaluate the efficacy of barrier creams on the level of skin penetration of chemicalsCONTACT DERMATITIS, Issue 1 2006Alexa Teichmann The reservoir function and the barrier function are important properties of the skin. The reservoir function is dependent on the barrier function which, however, needs support by protective measures, in particular under working conditions. Barrier creams represent a possibility to protect the skin. In the present study, a method was developed to investigate the effectiveness of reservoir closure by different formulations. Patent Blue V in water was used as a model penetrant. Its penetration, with and without barrier cream treatment, was analyzed by tape stripping in combination with UV/VIS spectroscopic measurements. The investigations showed that the stratum corneum represents a reservoir for topically applied Patent Blue V in water. Furthermore, the barrier investigations showed that vaseline and bees wax form a 100% barrier on the skin surface. The third barrier cream, containing waxes and surfactant, only partially showed a protective effect against the penetration of Patent Blue V in water. Strong interindividual differences were observed for this barrier product. In conclusion, it was assumed that the application of barrier creams cannot replace other protective measures and should be maximally used to inhibit low-grade irritants or in combination with other protectants or in body areas where other protective measures are not applicable. [source] Transmission of Ehrlichia risticii, the agent of Potomac horse fever, using naturally infected aquatic insects and helminth vectors: preliminary reportEQUINE VETERINARY JOURNAL, Issue 4 2000J. E. Madigan Summary Ehrlichia risticii, the agent of Potomac horse fever (PHF), has been recently detected in trematode stages found in snail secretions and in aquatic insects. Based on these findings, horses could conceivably be exposed to E. risticii by skin penetration with infected cercariae, by ingestion of infected cercariae in water or via metacercariae in a second intermediate host, such as an aquatic insect. In order to test this hypothesis, horses were challenged with infectious snail secretions and aquatic insects collected from a PHFendemic region in northern California. Two horses stood with their front feet in waterharbouring E. risticii -infected cercariae, 2 horses drank water harbouring E. risticii -infected cercariae, and 6 horses were fed pools of different aquatic insects harbouring E. risticii -infected metacercariae. In this preliminary study, only the one horse infected orally with mature caddisflies (Dicosmoecus gilvipes) developed the clinical and haematological disease syndrome of PHF. The agent was isolated from the blood of the infected horse in a continuous cell line and identified as E. risticii by characterisation of the 16S rRNA gene. Therefore, E. risticii is maintained in nature in a complex aquatic ecosystem and transmission to horses can occur through accidental ingestion of insects such as caddisflies containing infected metacercariae. At present, the small number of horses used in this study does not exclude other insects and free trematode stages as potential sources of infection. [source] The penetration enhancement and the lipolytic effects of TAT,GKH, both in in vitro, ex vivo, and in vivoINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 5 2004J. Lim It was demonstrated that the trans-activating transcriptional activator (TAT) protein from HIV-1 could enter cells when added to the surrounding media. TAT peptide chemically attached to various proteins was able to deliver these proteins to various cells and even at high levels in heart and spleen tissues in mice. In this study, the tri-peptide GKH (glycine,lysine,histidine) derived from the parathyroid hormone, which is known as a lipolytic peptide, was attached to 9-poly lysine (TAT) to be used as a cosmetic ingredient for eye-bag care product. When glycerol is released, expressed as the extracellular glycerol concentration (the so-called lipolysis index), TAT,GKH at 10,5m induces a maximal lipolytic effect of approximately 41.5% in epididymal adipocytes isolated from rats, compared with basal lipolysis. In a microdialysis study, TAT,GKH was perfused into epididymal adipose tissues of anaesthetized rats in increasing concentrations in a Ringer solution. The glycerol concentration in each dialysate was measured using an ultra-sensitive radiometric method. The perfusion of TAT,GKH induced a lipolytic effect. A penetration study showed that TAT,GKH resulted in a sevenfold higher penetration into excised hairless mice skin than GKH. An in vivo study showed that a TAT,GKH containing emulsion had a better effect upon the relative volume reduction of eye bag after 28 days of application on 22 healthy female volunteers than the placebo. It was therefore concluded that TAT,GKH increased skin penetration, which resulted in enhanced lipolytic effects in in vitro, ex vivo and in volume reduction of eye-bags in in vivo studies. [source] Percutaneous absorption and exposure assessment of pesticidesJOURNAL OF APPLIED TOXICOLOGY, Issue 2 2010Mai A. Ngo Abstract Dermal exposure to a diverse range of chemicals may result from various uses. In order to assess exposure and estimate potential risks, accurate quantitative data on absorption are required. Various factors will influence the final results and interpretations of studies designed to assess the ability of compounds to penetrate the skin. This overview will discuss skin penetration by pesticides, emphasizing key parameters to be considered from the perspective of exposure assessment. Copyright © 2009 John Wiley & Sons, Ltd. [source] Heterogeneity in skin treated with low-frequency ultrasoundJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2008Joseph Kushner IV Abstract Recent experimental evidence using colored, fluorescent permeants suggests that skin treated with low-frequency sonophoresis (LFS) is perturbed in a heterogeneous manner. Macroscopic and microscopic visualization studies, topical penetration studies, transdermal permeability studies, and skin electrical resistivity measurements have shown that discrete domains, referred to as localized transport regions (LTRs), which are formed during LFS treatment of the skin, possess greatly reduced barrier properties, and therefore exhibit increased permeant skin penetration, compared to the surrounding regions of LFS-treated skin. The transformation of LTR formation from a heterogeneous to a homogeneous phenomenon has the potential benefit of increasing the maximum level of transdermal permeability or of reducing the area of skin required to deliver a desired dose of drug transdermally. Future studies, aimed at elucidating both the mechanisms of LTR formation and the limits of nondamaging formation of LTRs in the skin, are required to incorporate these proposed improvements to enhance the efficacy and practical utility of low-frequency sonophoresis. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4119,4128, 2008 [source] Stability of 5-aminolevulinic acid in novel non-aqueous gel and patch-type systems intended for topical applicationJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2005Paul A. McCarron Abstract Aminolevulinic acid (ALA) stability within topical formulations intended for photodynamic therapy (PDT) is poor due to dimerisation to pyrazine-2,5-dipropionic acid (PY). Most strategies to improve stability use low pH vehicles, which can cause cutaneous irritancy. To overcome this problem, a novel approach is investigated that uses a non-aqueous vehicle to retard proton-induced charge separation across the 4-carbonyl group on ALA and lessen nucleophilic attack that leads to condensation dimerisation. Bioadhesive anhydrous vehicles based on methylvinylether-maleic anhydride copolymer patches and poly(ethyleneglycol) or glycerol thickened poly(acrylic acid) gels were formulated. ALA stability fell below pharmaceutically acceptable levels after 6 months, with bioadhesive patches stored at 5°C demonstrating the best stability by maintaining 86.2% of their original loading. Glycerol-based gels maintained 40.2% in similar conditions. However, ALA loss did not correspond to expected increases in PY, indicating the presence of another degradative process that prevented dimerisation. Nuclear magnetic resonance (NMR) analysis was inconclusive in respect of the mechanism observed in the patch system, but showed clearly that an esterification reaction involving ALA and both glycerol and poly(ethyleneglycol) was occurring. This was especially marked in the glycerol gels, where only 2.21% of the total expected PY was detected after 204 days at 5°C. Non-specific esterase hydrolysis demonstrated that ALA was recoverable from the gel systems, further supporting esterified binding within the gel matrices. It is conceivable that skin esterases could duplicate this finding upon topical application of the gel and convert these derivatives back to ALA in situ, provided skin penetration is not affected adversely. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:1756,1771, 2005 [source] Phycocyanin liposomes for topical anti-inflammatory activity: in-vitro in-vivo studiesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2009Maria Manconia Abstract Objectives The aim of this work was to investigate the anti-inflammatory activity of C-phycocyanin (C-PC) on skin inflammation after topical administration and the influence of liposomal delivery on its pharmacokinetic properties. Methods Liposomes of different size and structure were prepared with different techniques using soy phosphatidylcholine and cholesterol. Vesicular dispersions were characterised by transmission electron microscopy, optical and fluorescence microscopy for vesicle formation and morphology, dynamic laser light scattering for size distribution, and Zetasizer for zeta-potential. C-PC skin penetration and permeation experiments were performed in vitro using vertical diffusion Franz cells and human skin treated with either free or liposomal drug dispersed in a Carbopol gel. Key findings The protein was mainly localised in the stratum corneum, while no permeation of C-PC through the whole skin thickness was detected. Two percent C-PC-encapsulating liposomes showed the best drug accumulation in the stratum corneum and the whole skin, higher than that of the corresponding free 2% C-PC gel. Moreover, skin deposition of liposomal C-PC was dose dependent since skin accumulation values increased as the C-PC concentration in liposomes increased. The topical anti-inflammatory activity of samples was evaluated in vivo as inhibition of croton oil-induced or arachidonic acid-induced ear oedema in rats. Conclusions The results showed that C-PC can be successfully used as an anti-inflammatory drug and that liposomal encapsulation is effective in improving its anti-inflammatory activity. [source] Chronic Ethanol Consumption Decreases Murine Langerhans Cell Numbers and Delays Migration of Langerhans Cells as Well as Dermal Dendritic CellsALCOHOLISM, Issue 4 2008Kristin J. Ness Background:, Chronic alcoholics experience increased incidence and severity of infections, the mechanism of which is incompletely understood. Dendritic cells (DC) migrate from peripheral locations to lymph nodes (LN) to initiate adaptive immunity against infection. Little is known about how chronic alcohol exposure affects skin DC numbers or migration. Methods:, Mice received 20% EtOH in the drinking water for up to 35 weeks. Baseline Langerhans cell (LC) and dermal DC (dDC) numbers were enumerated by immunofluorescence (IF). LC repopulation after inflammation was determined following congenic bone marrow (BM) transplant and ultraviolet (UV) irradiation. Net LC loss from epidermis was determined by IF following TNF-, or CpG stimulation. LC and dDC migration into LN was assessed by flow cytometry following epicutaneous FITC administration. Results:, Chronic EtOH consumption caused a baseline reduction in LC but not dDC numbers. The deficit was not corrected following transplantation with non-EtOH-exposed BM and UV irradiation, supporting the hypothesis that the defect is intrinsic to the skin environment rather than LC precursors. Net loss of LC from epidermis following inflammation was greatly reduced in EtOH-fed mice versus controls. Ethanol consumption for at least 4 weeks led to delayed LC migration into LN, and consumption for at least 8 weeks led to delayed dDC migration into LN following epicutaneous FITC application. Conclusions:, Chronic EtOH consumption causes decreased density of epidermal LC, which likely results in decreased epidermal immunosurveillance. It also results in altered migratory responsiveness and delayed LC and dDC migration into LN, which likely delays activation of adaptive immunity. Decreased LC density at baseline appears to be the result of an alteration in the skin environment rather than an intrinsic LC defect. These findings provide novel mechanisms to at least partially explain why chronic alcoholics are more susceptible to infections, especially those following skin penetration. [source] Liposomes in investigative dermatologyPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 5 2001Daniel B. Yarosh Liposomes are microscopic spheres, usually composed of amphiphilic phospholipids. They may be useful without skin penetration if they simply protect or sequester compounds that would otherwise be unstable in the formulation. Liposomes that remain on the skin surface are useful as light-absorbers, agents to deliver color or sunscreens, or as depots for timed-release. Liposomes that penetrate the stratum corneum have the potential to interact with living tissue. Topically applied liposomes can either mix with the stratum corneum lipid matrix or penetrate the stratum corneum by exploiting the lipid-water interface of the intercellular matrix. There are at least four major routes of entry into the skin: pores, hair follicles, columnular spaces and the lipid:water matrix between squames. A major force driving liposome penetration is the water gradient, and flexible liposomes are best able to exploit these delivery opportunities. Some liposomes release their contents extracellularly. Topical application of photosensitizers may be enhanced by encapsulation in liposomes. Higher and longer-lasting drug concentrations may be produced in localized areas of skin, particularly at disease sites where the stratum corneum and the skin barrier function are disrupted. The liposome membrane should be designed to capture lipophilic drugs in the membrane or hydrophilic drugs in the interior. Other types of liposomes can be engineered to be taken up by cells. Once inside cells, the lysosomal sac and clatherin-coated pit are the dead-end destinations for liposomes unless an escape path has been engineered into the liposome. A novel method has been developed to allow delivery into cells of the skin, by escape from the lysosomal sac. These liposomes have been used to topical deliver active DNA repair enzymes from liposomes into epidermal cells and to enhance DNA repair of UV-irradiated skin. From these studies a tremendous amount has been learned about the relationship of DNA damage and skin cancer. Both mutations and immunosuppression appear to be essential to skin cancer and both are induced by DNA damage. DNA damage produces immediate effects by inducing the expression of cytokines, which means that DNA damage can induce signaling in neighboring, undamaged cells. The repair of only a fraction of the DNA damage has a disproportionate effect on the biological responses, clearly demonstrating that not all DNA damage is equivalent. This technology demonstrates that biologically active proteins can be delivered into the cells of skin, and opens up a new field of correcting or enhancing skin cell metabolism to improve human health. [source] Skin disposition of menthol after its application in the presence of drug substancesBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 8 2008Krzysztof Cal Abstract Many drug products that are applied onto the skin contain menthol. Menthol plays a dual role in the analgesic and anti-inflammatory drugs: it causes cooling and local anesthetic effects and, being a penetration enhancer, it increases the skin permeation of the drug substances. However, there are no data concerning the skin penetration of menthol after its application in the most commonly used vehicles and in the presence of drug substances. Therefore, this study evaluated the ex vivo skin disposition of menthol after application of the commercially available drug products containing aluminum acetotartrate, methyl salicylate, ibuprofen and naproxen, using full human-skin mounted in flow-through diffusion cells. After 15, 30 and 60,min of application, the skin was progressively tape-stripped into three fractions of stratum corneum and the remaining epidermis with dermis. The content of menthol in the skin layers was determined by GC method. Varying degrees of penetration of menthol into the skin layers was observed, depending on its amount in the vehicle and the presence of drug substance. In the presence of aluminum acetotartrate, the skin penetration of menthol was limited only to the outer fraction of the stratum corneum. In the case of drug products containing naproxen, the concentration of the drug substance significantly influenced the skin penetration of menthol. Copyright © 2008 John Wiley & Sons, Ltd. [source] Mechanism of tyrosinase inhibition by deoxyArbutin and its second-generation derivativesBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2008S. Chawla Summary Background, Disorders, such as age spots, melasma and hyperpigmentation at sites of actinic damage, emanate from the augmentation of an increased amount of epidermal melanin. Objectives, The ineptness of current therapies in treating these conditions, as well as high cytotoxicity, mutagenicity, poor skin penetration and low stability of skin-depigmenting formulations led us to investigate new compounds that meet the medical requirements for depigmentation agents. We have shown previously that the tyrosinase inhibitor deoxyArbutin (dA) is a more effective and less toxic skin lightener than hydroquinone (HQ). Methods, The efficacy and reversibility of dA and its derivatives on inhibiting tyrosine hydroxylase and DOPAoxidase was assessed using standard assays. Results, dA and its second-generation derivatives inhibit tyrosine hydroxylase and DOPAoxidase activities of tyrosinase dose dependently thereby inhibiting melanin synthesis in intact melanocytes, when used at concentrations that retain 95% cell viability in culture. This depigmenting effect was completely reversible when the compounds were removed. Tyrosinase inhibition was also observed in vitro when tested using human and purified mushroom tyrosinase, establishing that they are direct enzyme inhibitors. Lineweaver,Burk reciprocal plot analysis using mushroom tyrosinase illustrated that dA and its derivatives are more robust competitive inhibitors than HQ, when tyrosine is used as substrate. Conclusions, Thus, dA and its second-generation derivatives, which inhibit melanogenesis at safe concentrations by specifically acting on the tyrosinase enzyme at a post-translational level, are promising agents to ameliorate hyperpigmented lesions or lighten skin. [source] Contact allergy: the role of skin chemistry and metabolismCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 2 2003C. K. Smith Pease Summary Chemical reactivity plays the driving role in the biological processes that result in the induction of allergic contact dermatitis. This paper presents an overview of the chemical basis of allergic contact dermatitis, including the physicochemical parameters governing skin penetration, chemical reaction mechanisms associated with haptenation of skin proteins, (quantitative) structure,activity relationships (Q)SARs for contact allergens and prohaptens/skin metabolism of contact allergens. Despite the complexities and poor understanding of some of the metabolic processes leading to skin sensitization, it is possible to describe some of the relationships between chemical structures and the ability to form covalent conjugates with proteins. This knowledge, which relates chemical structure to a specific endpoint, can be programmed into an expert system. The Deductive Estimation of Risk from Existing Knowledge (DEREK) is one such expert system which is described in further detail. [source] | |||||||||||||