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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
11

Testování transdermální permeace vybraných xenobiotik / Testing of transdermal permeation of selected xenobiotics

Stará, Veronika January 2016 (has links)
This thesis first briefly mentions the characteristics of the skin and contains a review of current knowledge on the in vitro permeation testing of drugs through the skin. It describes the basic data about nerve agents and the possibilities of prophylaxis poisoning warfare agents focusing on preventive transdermal administration. The experimental work is focused on in vitro testing abilities oxime HI-6 and posibly other reactivators enzyme acetylcholinesterase penetrate through pig skin. Experiments were conducted in static diffusion cells Franz type. The amount of test substance leaked through the skin is determined in the sample of receptor fluid by HPLC. Keywords permeation in vitro; transdermal; pig skin; Franz cell; substance HI-6; antidota; nerve agents; acetylcholinesterase
12

Oxygen Diffusion Characterization of FRP Composites Used in Concrete Repair and Rehabilitation

Khoe, Chandra K. 01 January 2011 (has links)
Many independent studies have conclusively demonstrated that fiber reinforced polymers (FRP) slow down chloride-induced corrosion of steel in concrete. The mechanism for this slow down is not well understood but it has been hypothesized that FRP serves as a barrier to the ingress of chloride, moisture, and oxygen that sustain electrochemical corrosion of steel. This dissertation presents results from an experimental study that determined the oxygen permeation rates of materials used in infrastructure repair. In the study, the oxygen permeation constants for epoxy, carbon and glass fiber laminates, concrete, epoxy-concrete and FRP-concrete systems were determined and a method developed to use these results for designing the corrosion repair of FRP-concrete systems. A new diffusion cell was developed that could be used to test both thin polymer specimens and much thicker FRP-concrete specimens. Concentration gradients were introduced by exposing one face of the specimen to air and the other face continuously to 100% oxygen for the duration of the test to achieve steady state conditions. Partial pressures on the two surfaces were measured using electronic sensors and oxygen permeation constants extracted from the data using a quasi-steady state theoretical model based on Fick's law. Results obtained using this system were in agreement with published data for specimens such as Teflon and Polyethylene Terephthalate (PET) Mylar whose oxygen permeation constant is available in the published literature. Following the successful calibration of the system, oxygen permeation constants for epoxy, Carbon Fiber Reinforced Polymer (CFRP) and Glass Fiber Reinforced Polymer (GFRP) laminates were determined. It was found that the oxygen permeation constant for epoxies was an order of magnitude lower than that for FRP. Furthermore, two layer FRP laminates were found to be more permeable than single layer laminates. This finding had been reported previously in the literature but had been considered anomalous. Scanning electron micrographs showed that this was due to the wet layup process that inevitably trapped air between the multiple FRP layers. The oxygen permeability of FRP-concrete systems was evaluated for three different water-cementitious ratios of 0.4, 0.45 and 0.50 for both CFRP and GFRP materials. Results showed that the performance of CFRP and GFRP were comparable and the best results were obtained when FRP was used with concrete with the highest water-cementitious ratio. A simple design method is proposed to apply the findings from the research. This uses the concept of an equivalent FRP thickness derived following Fick's law. The findings from the research can be used to optimize FRP applications in corrosion repair. The experimental set up can easily be adapted to measure diffusion of carbon dioxide through FRP and other materials. This has potential applications in other disciplines, e.g. climate change.
13

Liberação e permeação in vitro de produtos transdérmicos: um estudo metodológico de aparatos e de condições experimentais / In vitro release and permeation transdermal products: evaluation of methods and apparatus

Praça, Fabíola Silva Garcia 24 August 2010 (has links)
Liberação transdérmica de fármacos apresenta várias vantagens na terapêutica quando comparada com administração oral ou parenteral. Não existe até o momento nenhum método previsto na Farmacopéia Brasileira para realizar testes de liberação de fármacos em adesivos transdérmicos, outros compêndios oficiais como Farmacopéia Americana, Britânica e Européia, descrevem o aparato de pás sobre disco, o cilindro rotatório e o suporte recíproco. Atualmente a literatura descreve diversos tipos de células de difusão para liberação transdérmica das quais a célula de difusão de Franz tem sido a mais empregada tanto para adesivos transdérmicos como formas semi-sólidas, utilizada no desenvolvimento farmacotécnico, caracterização biofarmacêutica e controle de qualidade. A proposta deste estudo tem por objetivo estipular critérios para a escolha mais adequada do equipamento e metodologias in vitro na avaliação da liberação transdérmicas de fármacos, utilizando a nicotina como fármaco modelo. Para tal, foram empregados ensaios in vitro de liberação e retenção cutânea utilizando métodos de pás sobre disco e método de célula de difusão de Franz modificada em sistema estático e fluxo contínuo. A validação dos fatores que influenciam a taxa de liberação in vitro da nicotina foram fundamentais para escolha do meio receptor, escolha da velocidade de agitação que promoveu mais semelhança no perfil de liberação em diferentes equipamentos assim como a escolha da membrana biológica mais adequada para o método proposto. Os resultados mais promissores foram selecionados para os ensaios in vitro de liberação, permeação e retenção cutânea. Os dados de liberação, tanto em quantidades de nicotina liberada como seu fluxo, demonstraram semelhança no uso de diferentes equipamentos, indicando possíveis intercambialidades entre os métodos propostos para liberação de nicotina transdérmica. Ensaios in vitro de permeação cutânea em célula de difusão vertical de Franz não demonstraram diferenças significativas em diferentes modelos de membranas biológicas utilizadas, as quais foram pele de orelha de porco, pele de camundongo sem pelo e pele de cobra cascavel hidratada por 24 horas. A quantidade de nicotina permeada em até 8 horas, assim como o fluxo de permeação foram significativamente menor para o método de pás sobre disco (FDA) quando comparado com os resultados obtidos utilizando célula de difusão vertical de Franz tanto em sistema estático com em fluxo contínuo. Estes resultados podem estar relacionados com a estrutura física do equipamento de célula de difusão vertical de Franz, uma vez que oferece um sistema oclusivo, dificultando o contato do adesivo com o meio receptor. Desta forma, os resultados deste projeto podem indicar o uso da célula de difusão vertical de Franz para ensaios in vitro de liberação e permeação cutânea da nicotina em formas farmacêuticas transdérmicas, podendo ser aplicado em pesquisas de desenvolvimento de formulações, controle da qualidade e testes de Equivalência Farmacêutica para produtos genéricos. Os resultados desta pesquisa apresentam-se podem ter importante influência nas discussões em torno dos medicamentos genéricos no Brasil, bem como na elaboração de diretrizes para testes de Equivalência Farmacêutica e Controle de Qualidade de medicamentos transdérmicos. Poderão ainda fornecer dados para indicações de protocolos para Farmacopéia Brasileira e pesquisa científica em torno dos sistemas de liberação transdérmicas de fármacos. / The aim of this work was to compare in vitro release and permeation of nicotine from transdermal patch (TDS) using three different methods such as, FDA paddle method and both Vertical Diffusion Cell (VCD) static and continuous flux. We evaluated different kinds of membrane (hairless mouse, porcine ear skin and snake skin), different composition and pH of acceptor phases (0.01N isotonic phosphate buffer pH 7.4 (± 0.2), water, and HCL 0.025N), agitation of acceptor phase and batches of the transdermal patches. Profiles of release and permeation from all methods evaluated were linked statistically using linear regression and one-way ANOVA nonparametric assay. The 0.01N isotonic phosphate buffer pH 7.4 (± 0.2) improved greater release rate of nicotine than those obtained using HCL and water as acceptor phase. Cumulative released and permeated amounts of nicotine were almost equal for all methods evaluated and there is not significantly different (one-way ANOVA p 0.05) were observed after 8 h. However nicotine permeated fluxes (J) after 8 h were significantly higher using VDC than those obtained using FDA paddle method. Cumulative permeated amounts (reported to the effective surface area of the cells) were overestimated when skin permeation experiments were prolonged to 12 h, indicating that the actual diffusion surface area of NiQuitinTM exceeded the effective diffusion surface area of the cells. Reducing the trimmed TDS surface area led not only to a reduction of the cumulative permeated amounts, but also to a reduction of the flux at 12 h. In order to evaluate the edge effect on drug release flux studies were performed using static VDC. In vitro penetration studies using different membranes showed not significantly difference for ear pig skin, hairless mouse and snake skin at 8 h. However data obtained without membrane were about 1.25 times smaller than those obtained with biological membranes. These results demonstrated that NiQuitinTM TDS had dependent release of membrane at 8 h of permeation. In conclusion there is not significantly different for in vitro release and permeation amounts of nicotine from NiQuitinTM using VDC and FDA method. In term of release efficiency all methods released up to 80% of nicotine after 8 h. The results suggested the use of VDC as potential method to evaluate both in vitro release and skin permeation of nicotine in transdermal patches.
14

Study of the interest of using vesicular systems associated with a drug for dermatological applications./ Etude de lintérêt de lutilisation de systèmes vésiculaires associés à une molécule active dans le but dune application dermatologique.

Gillet, Aline 28 February 2011 (has links)
Vesicular delivery systems, like liposomes, represent an attractive approach to improving skin delivery of drugs. Liposomes are composed of one or several lipid bilayers surrounding an aqueous compartment. They are able to encapsulate hydrophilic compounds into their inner compartment and lipophilic compounds into their lipid bilayers. In the first part of this thesis, we developed a new dermal delivery system combining the advantages of cyclodextrin inclusion complexes and those of deformable liposomes. This system was called drugs-in-cyclodextrin-in-deformable liposome. Betamethasone was chosen as the model drug. These systems were successfully developed and characterised. In vitro diffusion studies using Franz diffusion cells and polycarbonate membranes gave promising results. In order to better mimic the in vivo conditions, ex vivo penetration studies using pig ear skin and Franz diffusion cells were developed. The tape stripping method was used to determine the amount of drug in the stratum corneum. The amount of drug in the epidermis, dermis and receptor medium was also assayed. These methods were successfully validated. Unfortunately, ex vivo penetration studies of the developed skin delivery system could not confirm the promising in vitro results. Our research was then directed towards studies allowing a better understanding of liposome skin penetration mechanisms. In the second part of this thesis, the influence of several parameters on the skin penetration behaviour of liposomes was investigated. The formulation importance on skin penetration efficiency was highlighted by the comparison of two liposomal systems. In the first system, betamethasone is encapsulated by the help of cyclodextrin inclusion complexes in the aqueous compartment. In the second system, betamethasone is encapsulated alone in the lipid bilayer. The second system shows high membrane permeability of the encapsulated betamethasone. Despite this decreased drug retention, the second system enhances the skin penetration of betamethasone. This high membrane permeability and the better penetration of the second formulation support the mechanism of penetration as a free drug substance. In addition, no difference in penetration is observed between liposomes containing betamethasone alone and a non liposomal dispersion. Several surfactants or edge activators were incorporated in the lipid bilayer of liposomes in order to obtain deformable liposomes. Unfortunately, these deformable liposomes are unable to enhance skin penetration compared to classical non deformable liposomes. The addition of charged lipids in the lipid bilayer of liposomes encapsulating either betamethasone or betamethasone dipropionate was investigated. The addition of negatively charged lipids enhances the penetration of the encapsulated drug. The use of negatively charged liposomes enhanced the epidermis accumulation of betamethasone 9.3 times compared with the ethanolic solution. This improvement is not observed with the corresponding non liposomal dispersion, indicating that the vesicle form is of high importance. In the case of the ester, the use of negatively charged liposomes enhances the epidermis accumulation 5.5 times compared with the Diprosone® lotion and only 1.6 times compared with the ethanolic solution. The penetration of a more lipophilic drug, with a high intrinsic penetration, is less enhanceable when incorporated in liposomes. Confocal microscopy was performed to visualise skin penetration of fluorescently labelled liposomes. The lipophilic dye rhodamine B encapsulated in the lipid bilayer as betamethasone penetrates the epidermis at the same level as NBD-phosphatidylcholine. On the other hand, the hydrophilic dye calcein encapsulated in the aqueous compartment as betamethasone-cyclodextrin complexes does not penetrate the epidermis. These observations seem to confirm the ex vivo results. In addition, the skin penetration of rhodamine B seems to be improved by the incorporation in negatively charged liposomes compared with classical ones. Finally, the efficiency of the negatively charged vesicles was evaluated in vivo on volunteers by the skin blanching assay. Carbomer gel containing the negatively charged vesicles seems to enhance the blanching response of encapsulated betamethasone in comparison with the ethanolic hydroxypropylcellulose gel. However, results are not significantly different. This could be explained by the small number of volunteers. On the other hand, in the case of formulations containing betamethasone dipropionate, no tendency could be highlighted. These results seem to confirm that the use of negatively charged liposomes is more attractive for improving the efficiency of a lesser lipophilic drug, betamethasone, in comparison with the more lipophilic ester, betamethasone dipropionate. These results need to be confirmed using a higher number of volunteers./ Les systèmes vésiculaires, comme les liposomes, représentent une approche intéressante pour améliorer ladministration cutanée de médicaments. Les liposomes sont des vésicules sphériques composées dune ou plusieurs bicouches lipidiques entourant une cavité aqueuse. Ils sont capables dencapsuler des molécules hydrophiles dans leur cavité aqueuse, ainsi que de retenir des molécules hydrophobes dans leur bicouche lipidique. Dans la première partie de la thèse, nous nous sommes intéressés au développement dun nouveau système dadministration cutanée combinant les avantages des complexes dinclusion dans les cyclodextrines et ceux des liposomes déformables, aboutissant à un nouveau concept appelé : « drugs-in-cyclodextrin-in-deformable liposome». La bétaméthasone a été utilisée comme molécule modèle. Ces nouveaux systèmes ont été mis au point et caractérisés avec succès. Les premières études de diffusion réalisées in vitro, à travers des membranes synthétiques et au moyen des cellules de diffusion de Franz, étaient prometteuses. Afin de se rapprocher des conditions in vivo, des études de pénétration des liposomes ont alors été mises au point, ex-vivo, au moyen de cellules de diffusion et à travers des peaux doreilles de cochons. La méthode du « tape stripping » a permis de déterminer la quantité de bétaméthasone dans le stratum corneum. La quantité de substance active dans lépiderme, le derme et le mileu récepteur des cellules de Franz a également été déterminée. Ces méthodes ont été validées avec succés. Malheureusement, les études sur peaux doreilles de cochons nont pas permis de confirmer nos premières conclusions. Les recherches ont alors été orientées vers des études permettant de mieux comprendre les mécanismes de pénétration cutanée des liposomes. Dans la seconde partie de la thèse, linfluence de différents paramètres sur la pénétration cutanée a été étudiée. La comparaison de la pénétration cutanée de deux systèmes liposomiaux différents a mis en évidence limportance de la formulation des liposomes sur leur efficacité. Dans le premier, la bétaméthasone est encapsulée comme précédemment à laide de cyclodextrines dans la cavité aqueuse des liposomes déformables. Dans le second système, la bétaméthasone est encapsulée seule au niveau de la bicouche lipidique des liposomes. Ce second système a montré une plus grande perméabilité de la molécule modèle encapsulée. Malgré cette plus faible rétention, le deuxième système a permis daugmenter la pénétration de la molécule modèle. La plus grande perméabilité et la meilleure pénétration du deuxième système permettent de conclure que la bétaméthasone pénétrerait sous une forme non encapsulée dans les liposomes. De plus, aucune différence na été observée entre la pénétration cutanée des liposomes encapsulant la bétaméthasone dans leur bicouche et une dispersion non liposomale. Plusieurs tensio-actifs ont également été incorporés au niveau de la bicouche des liposomes afin dobtenir des liposomes déformables. Malheureusement, la faible augmentation de pénétration observée par rapport aux liposomes classiques non déformables nest pas significative. Lajout de lipides chargés au niveau de la bicouche lipidique de liposomes encapsulant soit la bétaméthasone soit le dipropionate de bétaméthasone a été investigué. Laddition de lipides chargés négativement a permis daugmenter la pénétration de la molécule encapsulée. Lutilisation de liposomes chargés négativement a permis daugmenter la quantité de bétaméthasone au niveau de lépiderme dun facteur 9,3 par rapport à une solution éthanolique de bétaméthasone. Cette augmentation na pas été observée avec la dispersion non liposomale correspondante, indiquant que la formulation sous forme de vésicules est très importante. En ce qui concerne le dipropionate de bétaméthasone, lencapsulation dans les liposomes chargés négativement a augmenté la quantité dester dans lépiderme dun facteur 5,5 par rapport à la spécialité Diprosone® lotion et seulement dun facteur 1,6 par rapport à la solution éthanolique. Lencapsulation dans les liposomes chargés négativement semble donc moins avantageuse dans le cas dune molécule plus lipophile, comme le dipropionate de bétaméthasone et qui possède déjà une bonne pénétration cutanée intrinsèque par rapport à une molécule plus hydrophile comme la bétamethasone. La pénétration de liposomes rendus fluorescents a été visualisée grâce à la microscopie confocale. Un marqueur lipophile, la rhodamine B, encapsulé dans la bicouche comme la bétaméthasone, pénètre bien dans la peau de la même façon que la phosphatidylcholine fluorescente. Par contre, un marqueur hydrophile, la calcéine, encapsulé dans la cavité des liposomes comme les complexes bétaméthasone-cyclodextrines, ne pénètre pas dans lépiderme. Ces observations confirment les résultats de dosage ex vivo au moyen des cellules de Franz. De plus, la pénétration dans la peau de la rhodamine B semble être plus importante lorsquelle est encapsulée dans les liposomes chargés négativement par rapport aux liposomes non chargés. Enfin, lefficacité des liposomes négatifs a été évaluée in vivo sur des volontaires grâce à lévaluation du pouvoir de blanchiement des corticostéroïdes. Le gel de carbomère contenant les liposomes chargés négativement semble augmenter la réponse de la bétaméthasone par rapport au gel éthanolique dhydroxypropylcellulose. Cependant, les résultats ne sont pas significatifs. Une explication pourrait être le faible nombre de volontaires. Par contre, dans le cas des liposomes contenant le dipropionate de bétaméthasone, il a été plus difficile de dégager une tendance. Ces résultats semblent confirmer que lutilisation des liposomes chargés négativement est plus intéressante dans le cas dune molécule moins lipophile comme la bétamethasone par rapport à une molécule plus lipophile comme le dipropionate de bétaméthasone. Ces résultats nécessitent cependant dêtre confirmés sur un plus grand nombre de volontaires.
15

Liberação e permeação in vitro de produtos transdérmicos: um estudo metodológico de aparatos e de condições experimentais / In vitro release and permeation transdermal products: evaluation of methods and apparatus

Fabíola Silva Garcia Praça 24 August 2010 (has links)
Liberação transdérmica de fármacos apresenta várias vantagens na terapêutica quando comparada com administração oral ou parenteral. Não existe até o momento nenhum método previsto na Farmacopéia Brasileira para realizar testes de liberação de fármacos em adesivos transdérmicos, outros compêndios oficiais como Farmacopéia Americana, Britânica e Européia, descrevem o aparato de pás sobre disco, o cilindro rotatório e o suporte recíproco. Atualmente a literatura descreve diversos tipos de células de difusão para liberação transdérmica das quais a célula de difusão de Franz tem sido a mais empregada tanto para adesivos transdérmicos como formas semi-sólidas, utilizada no desenvolvimento farmacotécnico, caracterização biofarmacêutica e controle de qualidade. A proposta deste estudo tem por objetivo estipular critérios para a escolha mais adequada do equipamento e metodologias in vitro na avaliação da liberação transdérmicas de fármacos, utilizando a nicotina como fármaco modelo. Para tal, foram empregados ensaios in vitro de liberação e retenção cutânea utilizando métodos de pás sobre disco e método de célula de difusão de Franz modificada em sistema estático e fluxo contínuo. A validação dos fatores que influenciam a taxa de liberação in vitro da nicotina foram fundamentais para escolha do meio receptor, escolha da velocidade de agitação que promoveu mais semelhança no perfil de liberação em diferentes equipamentos assim como a escolha da membrana biológica mais adequada para o método proposto. Os resultados mais promissores foram selecionados para os ensaios in vitro de liberação, permeação e retenção cutânea. Os dados de liberação, tanto em quantidades de nicotina liberada como seu fluxo, demonstraram semelhança no uso de diferentes equipamentos, indicando possíveis intercambialidades entre os métodos propostos para liberação de nicotina transdérmica. Ensaios in vitro de permeação cutânea em célula de difusão vertical de Franz não demonstraram diferenças significativas em diferentes modelos de membranas biológicas utilizadas, as quais foram pele de orelha de porco, pele de camundongo sem pelo e pele de cobra cascavel hidratada por 24 horas. A quantidade de nicotina permeada em até 8 horas, assim como o fluxo de permeação foram significativamente menor para o método de pás sobre disco (FDA) quando comparado com os resultados obtidos utilizando célula de difusão vertical de Franz tanto em sistema estático com em fluxo contínuo. Estes resultados podem estar relacionados com a estrutura física do equipamento de célula de difusão vertical de Franz, uma vez que oferece um sistema oclusivo, dificultando o contato do adesivo com o meio receptor. Desta forma, os resultados deste projeto podem indicar o uso da célula de difusão vertical de Franz para ensaios in vitro de liberação e permeação cutânea da nicotina em formas farmacêuticas transdérmicas, podendo ser aplicado em pesquisas de desenvolvimento de formulações, controle da qualidade e testes de Equivalência Farmacêutica para produtos genéricos. Os resultados desta pesquisa apresentam-se podem ter importante influência nas discussões em torno dos medicamentos genéricos no Brasil, bem como na elaboração de diretrizes para testes de Equivalência Farmacêutica e Controle de Qualidade de medicamentos transdérmicos. Poderão ainda fornecer dados para indicações de protocolos para Farmacopéia Brasileira e pesquisa científica em torno dos sistemas de liberação transdérmicas de fármacos. / The aim of this work was to compare in vitro release and permeation of nicotine from transdermal patch (TDS) using three different methods such as, FDA paddle method and both Vertical Diffusion Cell (VCD) static and continuous flux. We evaluated different kinds of membrane (hairless mouse, porcine ear skin and snake skin), different composition and pH of acceptor phases (0.01N isotonic phosphate buffer pH 7.4 (± 0.2), water, and HCL 0.025N), agitation of acceptor phase and batches of the transdermal patches. Profiles of release and permeation from all methods evaluated were linked statistically using linear regression and one-way ANOVA nonparametric assay. The 0.01N isotonic phosphate buffer pH 7.4 (± 0.2) improved greater release rate of nicotine than those obtained using HCL and water as acceptor phase. Cumulative released and permeated amounts of nicotine were almost equal for all methods evaluated and there is not significantly different (one-way ANOVA p 0.05) were observed after 8 h. However nicotine permeated fluxes (J) after 8 h were significantly higher using VDC than those obtained using FDA paddle method. Cumulative permeated amounts (reported to the effective surface area of the cells) were overestimated when skin permeation experiments were prolonged to 12 h, indicating that the actual diffusion surface area of NiQuitinTM exceeded the effective diffusion surface area of the cells. Reducing the trimmed TDS surface area led not only to a reduction of the cumulative permeated amounts, but also to a reduction of the flux at 12 h. In order to evaluate the edge effect on drug release flux studies were performed using static VDC. In vitro penetration studies using different membranes showed not significantly difference for ear pig skin, hairless mouse and snake skin at 8 h. However data obtained without membrane were about 1.25 times smaller than those obtained with biological membranes. These results demonstrated that NiQuitinTM TDS had dependent release of membrane at 8 h of permeation. In conclusion there is not significantly different for in vitro release and permeation amounts of nicotine from NiQuitinTM using VDC and FDA method. In term of release efficiency all methods released up to 80% of nicotine after 8 h. The results suggested the use of VDC as potential method to evaluate both in vitro release and skin permeation of nicotine in transdermal patches.
16

In Vitro Percutaneous Absorption Studies of Cannabidiol Using Human Skin: Exploring the Effect of Drug Concentration, Chemical Enhancers, and Essential Oils

Junaid, Mohammad S., Tijani, Akeemat O., Puri, Ashana, Banga, Ajay K. 25 March 2022 (has links)
Cannabidiol, a non-psychoactive constituent of cannabis, has garnered much attention after United States Food and Drug Administration approved Epidiolex® for oral use. Although therapeutic effect of cannabidiol after systemic absorption has been investigated extensively, its therapeutic potential in treating skin disorders after local delivery still needs further exploration. Our study has investigated the effect of cannabidiol concentration, chemical enhancers, and essential oils on percutaneous absorption of cannabidiol. In vitro permeation tests were conducted on human skin. The 24 h study results suggest no significant difference in amount of drug absorbed into skin, between 5% (242.41 ± 12.17 µg/cm) and 10% (232.79 ± 20.82 cm) cannabidiol solutions. However, 1% delivered (23.02 ± 4.74 µg/cm) significantly lower amount of drug into skin than 5% and 10%. Transcutol and isopropyl myristate did not enhance delivery of cannabidiol. However, oleic acid was found to be useful as chemical enhancer. Oleic acid (43.07 ± 10.11 µg/cm) had significantly higher cannabidiol delivery into skin than the group without oleic acid (10.98 ± 3.40 µg/cm) after a 4 h in vitro permeation study. Essential oils at concentrations tested had lower total cannabidiol delivery when compared to control. This study's findings will help guide future research on the pharmacological effect of percutaneously delivered cannabidiol on inflammatory skin disorders.
17

In vitro skin permeation of selected platinum group metals / Anja Franken

Franken, Anja January 2014 (has links)
Background: Platinum group metal (PGM) mining and refining is a large constituent of the mining sector of South Africa and contributes significantly to the gross domestic product. The PGMs include the rare metals platinum (Pt), palladium (Pd), rhodium (Rh), ruthenium (Ru), iridium (Ir) and osmium (Os). During the refining process workers are potentially exposed to various chemical forms of the PGMs via the respiratory and dermal exposure routes. Historically, emphasis has been on respiratory exposure while the extent of skin exposure is still unknown. Among the different forms of PGMs, the salts are potential sensitisers, with platinum being a known respiratory sensitiser. Workers occupationally exposed to platinum and rhodium have reported respiratory as well as skin symptoms. However, it is unknown if these metals in the salt form are permeable through human skin, and whether dermal exposure could contribute to sensitisation. Evidence regarding differences between African and Caucasian skin anatomy and structure, as well as permeation through skin is contradictory, and no information is available on metal permeation through African skin. The in vitro diffusion method has been utilised successfully in occupational toxicology to demonstrate that metals such as chromium, cobalt and nickel, to name a few, permeate through human skin. The permeability of platinum and rhodium has not been investigated previously. Aims and objectives: The research aim was to obtain insight into the permeability of platinum and rhodium through intact human skin and to provide information needed to determine the potential health risk following dermal exposure to these metals. The specific objectives included: (i) to critically review the in vitro diffusion method that is used to determine the permeability of metals through human skin, (ii) to investigate the permeation of potassium tetrachloroplatinate (K2PtCl4) and rhodium chloride (RhCl3) as representative PGM salts through intact human skin over a 24-hour period, (iii) to evaluate the difference in permeability of platinum and rhodium through intact human skin, (iv) to evaluate the difference in permeability of platinum through intact African and Caucasian human skin. Methods: Abdominal skin obtained after cosmetic procedures was obtained from five female Caucasian and three female African donors between the ages of 28 and 52 with ethical approval from the North-West University. Full thickness skin tissue was mounted in a vertical Franz diffusion cell. Skin integrity was tested by measuring the electrical resistance across the skin before and after conclusion of the experiments, using a Tinsley LCR Data bridge Model 6401. The donor solution of 32.46 mg K2PtCl4 in 50 ml of synthetic sweat (pH 6.5), and 43.15 mg RhCl3 in 50 ml of synthetic sweat (pH 6.5) was prepared. The donor solution was applied to the stratum corneum side of the skin and physiological receptor solution (pH 7.35) was added to the receptor compartment. The concentration of the metals in the receptor solution was determined by high resolution inductively coupled plasma-mass spectrometry after extraction at various intervals during the 24 hours of the study. After completion of the study, the skin was rinsed four times to remove any platinum or rhodium remaining on the skin surface. The skin was digested using hydrogen peroxide, nitric acid and hydrochloric acid during different steps to determine the mass of the metals remaining in the skin by inductively coupled plasma-optical emission spectrometry. Results: The comparison of published in vitro skin permeation studies involving metals is impeded by the variations in the experimental design and dissimilarity in the reporting of results. Differences in experimental design included, most noticeably, the use of various donor and receptor solutions, different temperatures wherein the receptor compartment was placed, differences in skin thickness and variations in exposed skin surface areas. The metals considered in the review, namely chromium, cobalt, gold, lead, mercury, nickel, platinum, rhodium and silver, permeate through intact human skin under physiological conditions. Large variations in the permeability results were observed, with the notable differences in methodology as the probable reason. Results obtained from the in vitro experiments indicate that platinum and rhodium permeated through intact Caucasian skin with flux values of 0.12 and 0.05 ng/cm2/h, respectively. The cumulative mass of platinum (2.57 ng/cm2) that permeated after 24 hours of exposure was statistically significantly (p = 0.016) higher than rhodium permeation (1.11 ng/cm2). The mass of platinum (1 459.47 ng/cm2) retained in the skin after 24 hours of exposure was statistically significantly (p < 0.001) higher than rhodium retention (757.04 ng/cm2). The comparison of permeability between two different racial groups indicates that platinum permeated through the skin of both racial groups with the flux through African skin found as 1.93 ng/cm2/h and 0.27 ng/cm2/h through Caucasian skin. The cumulative mass of platinum permeated after 24 hours of exposure was statistically significantly (p = 0.044) higher through African skin (37.52 ng/cm2) than Caucasian skin (5.05 ng/cm2). The retention of platinum in African skin (3 064.13 ng/cm2) was more than twice the mass retained in Caucasian skin (1 486.32 ng/cm2). Conclusions: The in vitro diffusion method is an applicable method to determine skin permeability of metals. However, the experimental design and format of data reporting should be standardised to enable comparison of results from different studies. Platinum and rhodium permeated through intact human skin, with platinum permeation significantly higher. African skin was significantly more permeable by platinum than Caucasian skin. Both platinum and rhodium were retained inside the skin after 24 hours of exposure, possibly forming a reservoir which could contribute to continued permeation through the skin even after removal thereof from the skin. Platinum and rhodium permeated through full thickness skin and thereby could possibly contribute to local skin symptoms such as dermatitis and urticaria found in occupationally exposed workers. By permeating through the upper layers of the skin, these metals could potentially reach the viable epidermis and contribute to sensitisation. / PhD (Occupational Hygiene), North-West University, Potchefstroom Campus, 2015
18

In vitro skin permeation of selected platinum group metals / Anja Franken

Franken, Anja January 2014 (has links)
Background: Platinum group metal (PGM) mining and refining is a large constituent of the mining sector of South Africa and contributes significantly to the gross domestic product. The PGMs include the rare metals platinum (Pt), palladium (Pd), rhodium (Rh), ruthenium (Ru), iridium (Ir) and osmium (Os). During the refining process workers are potentially exposed to various chemical forms of the PGMs via the respiratory and dermal exposure routes. Historically, emphasis has been on respiratory exposure while the extent of skin exposure is still unknown. Among the different forms of PGMs, the salts are potential sensitisers, with platinum being a known respiratory sensitiser. Workers occupationally exposed to platinum and rhodium have reported respiratory as well as skin symptoms. However, it is unknown if these metals in the salt form are permeable through human skin, and whether dermal exposure could contribute to sensitisation. Evidence regarding differences between African and Caucasian skin anatomy and structure, as well as permeation through skin is contradictory, and no information is available on metal permeation through African skin. The in vitro diffusion method has been utilised successfully in occupational toxicology to demonstrate that metals such as chromium, cobalt and nickel, to name a few, permeate through human skin. The permeability of platinum and rhodium has not been investigated previously. Aims and objectives: The research aim was to obtain insight into the permeability of platinum and rhodium through intact human skin and to provide information needed to determine the potential health risk following dermal exposure to these metals. The specific objectives included: (i) to critically review the in vitro diffusion method that is used to determine the permeability of metals through human skin, (ii) to investigate the permeation of potassium tetrachloroplatinate (K2PtCl4) and rhodium chloride (RhCl3) as representative PGM salts through intact human skin over a 24-hour period, (iii) to evaluate the difference in permeability of platinum and rhodium through intact human skin, (iv) to evaluate the difference in permeability of platinum through intact African and Caucasian human skin. Methods: Abdominal skin obtained after cosmetic procedures was obtained from five female Caucasian and three female African donors between the ages of 28 and 52 with ethical approval from the North-West University. Full thickness skin tissue was mounted in a vertical Franz diffusion cell. Skin integrity was tested by measuring the electrical resistance across the skin before and after conclusion of the experiments, using a Tinsley LCR Data bridge Model 6401. The donor solution of 32.46 mg K2PtCl4 in 50 ml of synthetic sweat (pH 6.5), and 43.15 mg RhCl3 in 50 ml of synthetic sweat (pH 6.5) was prepared. The donor solution was applied to the stratum corneum side of the skin and physiological receptor solution (pH 7.35) was added to the receptor compartment. The concentration of the metals in the receptor solution was determined by high resolution inductively coupled plasma-mass spectrometry after extraction at various intervals during the 24 hours of the study. After completion of the study, the skin was rinsed four times to remove any platinum or rhodium remaining on the skin surface. The skin was digested using hydrogen peroxide, nitric acid and hydrochloric acid during different steps to determine the mass of the metals remaining in the skin by inductively coupled plasma-optical emission spectrometry. Results: The comparison of published in vitro skin permeation studies involving metals is impeded by the variations in the experimental design and dissimilarity in the reporting of results. Differences in experimental design included, most noticeably, the use of various donor and receptor solutions, different temperatures wherein the receptor compartment was placed, differences in skin thickness and variations in exposed skin surface areas. The metals considered in the review, namely chromium, cobalt, gold, lead, mercury, nickel, platinum, rhodium and silver, permeate through intact human skin under physiological conditions. Large variations in the permeability results were observed, with the notable differences in methodology as the probable reason. Results obtained from the in vitro experiments indicate that platinum and rhodium permeated through intact Caucasian skin with flux values of 0.12 and 0.05 ng/cm2/h, respectively. The cumulative mass of platinum (2.57 ng/cm2) that permeated after 24 hours of exposure was statistically significantly (p = 0.016) higher than rhodium permeation (1.11 ng/cm2). The mass of platinum (1 459.47 ng/cm2) retained in the skin after 24 hours of exposure was statistically significantly (p < 0.001) higher than rhodium retention (757.04 ng/cm2). The comparison of permeability between two different racial groups indicates that platinum permeated through the skin of both racial groups with the flux through African skin found as 1.93 ng/cm2/h and 0.27 ng/cm2/h through Caucasian skin. The cumulative mass of platinum permeated after 24 hours of exposure was statistically significantly (p = 0.044) higher through African skin (37.52 ng/cm2) than Caucasian skin (5.05 ng/cm2). The retention of platinum in African skin (3 064.13 ng/cm2) was more than twice the mass retained in Caucasian skin (1 486.32 ng/cm2). Conclusions: The in vitro diffusion method is an applicable method to determine skin permeability of metals. However, the experimental design and format of data reporting should be standardised to enable comparison of results from different studies. Platinum and rhodium permeated through intact human skin, with platinum permeation significantly higher. African skin was significantly more permeable by platinum than Caucasian skin. Both platinum and rhodium were retained inside the skin after 24 hours of exposure, possibly forming a reservoir which could contribute to continued permeation through the skin even after removal thereof from the skin. Platinum and rhodium permeated through full thickness skin and thereby could possibly contribute to local skin symptoms such as dermatitis and urticaria found in occupationally exposed workers. By permeating through the upper layers of the skin, these metals could potentially reach the viable epidermis and contribute to sensitisation. / PhD (Occupational Hygiene), North-West University, Potchefstroom Campus, 2015
19

Quantifying diffusion in biofilms : from model hydrogels to living biofilms

Golmohamadi, Mahmood 07 1900 (has links)
Les biofilms sont des communautés de microorganismes incorporés dans une matrice exo-polymérique complexe. Ils sont reconnus pour jouer un rôle important comme barrière de diffusion dans les systèmes environnementaux et la santé humaine, donnant lieu à une résistance accrue aux antibiotiques et aux désinfectants. Comme le transfert de masse dans un biofilm est principalement dû à la diffusion moléculaire, il est primordial de comprendre les principaux paramètres influençant les flux de diffusion. Dans ce travail, nous avons étudié un biofilm de Pseudomonas fluorescens et deux hydrogels modèles (agarose et alginate) pour lesquels l’autodiffusion (mouvement Brownien) et les coefficients de diffusion mutuels ont été quantifiés. La spectroscopie par corrélation de fluorescence a été utilisée pour mesurer les coefficients d'autodiffusion dans une volume confocal de ca. 1 m3 dans les gels ou les biofilms, tandis que les mesures de diffusion mutuelle ont été faites par cellule de diffusion. En outre, la voltamétrie sur microélectrode a été utilisée pour évaluer le potentiel de Donnan des gels afin de déterminer son impact sur la diffusion. Pour l'hydrogel d'agarose, les observations combinées d'une diminution du coefficient d’autodiffusion et de l’augmentation de la diffusion mutuelle pour une force ionique décroissante ont été attribuées au potentiel de Donnan du gel. Des mesures de l'effet Donnan (différence de -30 mV entre des forces ioniques de 10-4 et 10-1 M) et l'accumulation correspondante d’ions dans l'hydrogel (augmentation d’un facteur de 13 par rapport à la solution) ont indiqué que les interactions électrostatiques peuvent fortement influencer le flux de diffusion de cations, même dans un hydrogel faiblement chargé tel que l'agarose. Curieusement, pour un gel plus chargé comme l'alginate de calcium, la variation de la force ionique et du pH n'a donné lieu qu'à de légères variations de la diffusion de sondes chargées dans l'hydrogel. Ces résultats suggèrent qu’en influençant la diffusion du soluté, l'effet direct des cations sur la structure du gel (compression et/ou gonflement induits) était beaucoup plus efficace que l'effet Donnan. De même, pour un biofilm bactérien, les coefficients d'autodiffusion étaient pratiquement constants sur toute une gamme de force ionique (10-4-10-1 M), aussi bien pour des petits solutés chargés négativement ou positivement (le rapport du coefficient d’autodiffusion dans biofilm sur celui dans la solution, Db/Dw ≈ 85 %) que pour des nanoparticules (Db/Dw≈ 50 %), suggérant que l'effet d'obstruction des biofilms l’emporte sur l'effet de charge. Les résultats de cette étude ont montré que parmi les divers facteurs majeurs qui affectent la diffusion dans un biofilm environnemental oligotrophe (exclusion stérique, interactions électrostatiques et hydrophobes), les effets d'obstruction semblent être les plus importants lorsque l'on tente de comprendre la diffusion du soluté. Alors que les effets de charge ne semblaient pas être importants pour l'autodiffusion de substrats chargés dans l'hydrogel d'alginate ou dans le biofilm bactérien, ils ont joué un rôle clé dans la compréhension de la diffusion à travers l’agarose. L’ensemble de ces résultats devraient être très utiles pour l'évaluation de la biodisponibilité des contaminants traces et des nanoparticules dans l'environnement. / Biofilms are primarily communities of microorganisms embedded in a complex exopolymer matrix. They are thought to play an important role as diffusive barriers in environmental systems and human health, resulting in increased resistance to disinfectants and antibiotics. Since mass transport in a biofilm is primarily due to molecular diffusion, it is critical to understand the main parameters influencing diffusive fluxes in a biofilm. In this thesis, a Pseudomonas fluorescens biofilm and two model hydrogels, (agarose and calcium alginate), were investigated. Both self-diffusion (Brownian motion) and mutual diffusion coefficients were quantified. Fluorescence correlation spectroscopy was used to measure the self-diffusion coefficients in a ca. 1 m3 confocal volume in the gels or biofilms, whereas a diffusion cell setup was employed for mutual diffusion measurements. In addition, microelectrode voltammetry was used to evaluate Donnan potential of the gels in order to determine its impact on diffusion. For the agarose hydrogel, the combined observations of a decreasing self-diffusion coefficient coupled with increasing mutual diffusion as a function of a decreasing ionic strength have been attributed to the gel’s Donnan potential. Measurements of the Donnan effect (difference of -30 mV between ionic strengths of 10-4 and 10-1 M) and the corresponding accumulation of ions in the hydrogel (13x enhancement with respect to the bulk solution) indicated that electrostatic interactions can strongly influence the diffusive flux of cations, even in a weakly charged hydrogel, such as agarose. Somewhat surprisingly, for a more highly charged gel such as calcium alginate, varying ionic strength and pH resulted in only small changes to the diffusion of charged probes in the hydrogel. These results suggested that the direct effect of the cations on gel structure (due to an induced swelling or compression) was much more effective than the Donnan effect when influencing solute diffusion. Similarly, for a bacterial biofilm, self-diffusion coefficients were virtually constant across a range of examined ionic strengths (10-4-10-1 M) for both negatively and positively charged small solutes (Db/Dw≈85%) and nanoparticles (Db/Dw≈50%), suggesting that the obstruction effect of the biofilms again overwhelmed the charge effect. The results of this work indicated that among the various major factors affecting diffusion in an oligotrophic environmental biofilm (steric exclusion, hydrophobic and electrostatic interactions), obstruction effects appeared to be the most important when attempting to understand the solute diffusion. While charge effects did not appear to be important to the self-diffusion of charged substrates in the alginate hydrogel or bacterial biofilm, they were key to understanding diffusion through another gel, with numerous biomedical and environmental applications, i.e. agarose. These results should be extremely useful when evaluating the bioavailability of the trace contaminants and nanoparticles in the environment.
20

Quantifying diffusion in biofilms : from model hydrogels to living biofilms

Golmohamadi, Mahmood 07 1900 (has links)
Les biofilms sont des communautés de microorganismes incorporés dans une matrice exo-polymérique complexe. Ils sont reconnus pour jouer un rôle important comme barrière de diffusion dans les systèmes environnementaux et la santé humaine, donnant lieu à une résistance accrue aux antibiotiques et aux désinfectants. Comme le transfert de masse dans un biofilm est principalement dû à la diffusion moléculaire, il est primordial de comprendre les principaux paramètres influençant les flux de diffusion. Dans ce travail, nous avons étudié un biofilm de Pseudomonas fluorescens et deux hydrogels modèles (agarose et alginate) pour lesquels l’autodiffusion (mouvement Brownien) et les coefficients de diffusion mutuels ont été quantifiés. La spectroscopie par corrélation de fluorescence a été utilisée pour mesurer les coefficients d'autodiffusion dans une volume confocal de ca. 1 m3 dans les gels ou les biofilms, tandis que les mesures de diffusion mutuelle ont été faites par cellule de diffusion. En outre, la voltamétrie sur microélectrode a été utilisée pour évaluer le potentiel de Donnan des gels afin de déterminer son impact sur la diffusion. Pour l'hydrogel d'agarose, les observations combinées d'une diminution du coefficient d’autodiffusion et de l’augmentation de la diffusion mutuelle pour une force ionique décroissante ont été attribuées au potentiel de Donnan du gel. Des mesures de l'effet Donnan (différence de -30 mV entre des forces ioniques de 10-4 et 10-1 M) et l'accumulation correspondante d’ions dans l'hydrogel (augmentation d’un facteur de 13 par rapport à la solution) ont indiqué que les interactions électrostatiques peuvent fortement influencer le flux de diffusion de cations, même dans un hydrogel faiblement chargé tel que l'agarose. Curieusement, pour un gel plus chargé comme l'alginate de calcium, la variation de la force ionique et du pH n'a donné lieu qu'à de légères variations de la diffusion de sondes chargées dans l'hydrogel. Ces résultats suggèrent qu’en influençant la diffusion du soluté, l'effet direct des cations sur la structure du gel (compression et/ou gonflement induits) était beaucoup plus efficace que l'effet Donnan. De même, pour un biofilm bactérien, les coefficients d'autodiffusion étaient pratiquement constants sur toute une gamme de force ionique (10-4-10-1 M), aussi bien pour des petits solutés chargés négativement ou positivement (le rapport du coefficient d’autodiffusion dans biofilm sur celui dans la solution, Db/Dw ≈ 85 %) que pour des nanoparticules (Db/Dw≈ 50 %), suggérant que l'effet d'obstruction des biofilms l’emporte sur l'effet de charge. Les résultats de cette étude ont montré que parmi les divers facteurs majeurs qui affectent la diffusion dans un biofilm environnemental oligotrophe (exclusion stérique, interactions électrostatiques et hydrophobes), les effets d'obstruction semblent être les plus importants lorsque l'on tente de comprendre la diffusion du soluté. Alors que les effets de charge ne semblaient pas être importants pour l'autodiffusion de substrats chargés dans l'hydrogel d'alginate ou dans le biofilm bactérien, ils ont joué un rôle clé dans la compréhension de la diffusion à travers l’agarose. L’ensemble de ces résultats devraient être très utiles pour l'évaluation de la biodisponibilité des contaminants traces et des nanoparticules dans l'environnement. / Biofilms are primarily communities of microorganisms embedded in a complex exopolymer matrix. They are thought to play an important role as diffusive barriers in environmental systems and human health, resulting in increased resistance to disinfectants and antibiotics. Since mass transport in a biofilm is primarily due to molecular diffusion, it is critical to understand the main parameters influencing diffusive fluxes in a biofilm. In this thesis, a Pseudomonas fluorescens biofilm and two model hydrogels, (agarose and calcium alginate), were investigated. Both self-diffusion (Brownian motion) and mutual diffusion coefficients were quantified. Fluorescence correlation spectroscopy was used to measure the self-diffusion coefficients in a ca. 1 m3 confocal volume in the gels or biofilms, whereas a diffusion cell setup was employed for mutual diffusion measurements. In addition, microelectrode voltammetry was used to evaluate Donnan potential of the gels in order to determine its impact on diffusion. For the agarose hydrogel, the combined observations of a decreasing self-diffusion coefficient coupled with increasing mutual diffusion as a function of a decreasing ionic strength have been attributed to the gel’s Donnan potential. Measurements of the Donnan effect (difference of -30 mV between ionic strengths of 10-4 and 10-1 M) and the corresponding accumulation of ions in the hydrogel (13x enhancement with respect to the bulk solution) indicated that electrostatic interactions can strongly influence the diffusive flux of cations, even in a weakly charged hydrogel, such as agarose. Somewhat surprisingly, for a more highly charged gel such as calcium alginate, varying ionic strength and pH resulted in only small changes to the diffusion of charged probes in the hydrogel. These results suggested that the direct effect of the cations on gel structure (due to an induced swelling or compression) was much more effective than the Donnan effect when influencing solute diffusion. Similarly, for a bacterial biofilm, self-diffusion coefficients were virtually constant across a range of examined ionic strengths (10-4-10-1 M) for both negatively and positively charged small solutes (Db/Dw≈85%) and nanoparticles (Db/Dw≈50%), suggesting that the obstruction effect of the biofilms again overwhelmed the charge effect. The results of this work indicated that among the various major factors affecting diffusion in an oligotrophic environmental biofilm (steric exclusion, hydrophobic and electrostatic interactions), obstruction effects appeared to be the most important when attempting to understand the solute diffusion. While charge effects did not appear to be important to the self-diffusion of charged substrates in the alginate hydrogel or bacterial biofilm, they were key to understanding diffusion through another gel, with numerous biomedical and environmental applications, i.e. agarose. These results should be extremely useful when evaluating the bioavailability of the trace contaminants and nanoparticles in the environment.

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