Orientador: Mirna Lucia Gigante / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-12T19:47:23Z (GMT). No. of bitstreams: 1 Hatanaka_CamilaLie_M.pdf: 549349 bytes, checksum: c5f48036602609500f035f399d2cb21c (MD5) Previous issue date: 2009 / Resumo: Atualmente a adição de hidrocolóides é um recurso utilizado em produtos lácteos para modificar a textura ou evitar defeitos como a sinérese. Hidrocolóides são utilizados como agentes espessantes, gelificantes e estabilizantes, e podem apresentar características sinérgicas quando utilizados em conjunto. O objetivo deste trabalho foi avaliar o efeito da adição de goma tara e carragena sobre a sinérese do iogurte firme desnatado. Os iogurtes foram fabricados com leite desnatado reconstituído adicionado de goma tara e carragena, em concentrações variando de 0 a 0,0585%, em combinações previstas pela metodologia de superfície de resposta. Após aproximadamente 48 horas de armazenamento refrigerado, determinou-se a composição dos iogurtes e a sinérese, que foi avaliada de três formas distintas: sinérese espontânea, por drenagem e por centrifugação. A goma tara afetou significativamente a sinérese do produto, que aumentou em concentrações superiores a 0,0293%, independentemente da sua forma de avaliação. A sinérese não foi significativamente afetada pela adição de carragena e nem pela interação entre os polissacarídeos. As concentrações escolhidas para fabricação e avaliação dos iogurtes durante o armazenamento refrigerado (29 dias) foram iogurte controle (sem adição de polissacarídeos), iogurte com 0,02% de goma tara e iogurte com 0,02% de tara + 0,02% de carragena. Após aproximadamente 24 horas os iogurtes foram avaliados quanto à composição centesimal. Durante o armazenamento refrigerado, após 1, 8, 15, 22 e 29 dias de fabricação os produtos foram avaliados quanto à sinérese espontânea, firmeza, e pH para acompanhamento da pós-acidificação. A sinérese espontânea foi significativamente afetada pelos tratamentos, sendo que a menor liberação de soro foi observada para o iogurte fabricado com goma tara e carragena, enquanto que o iogurte que continha apenas goma tara apresentou maior sinérese. A firmeza foi significativamente afetada pelos tratamentos. O iogurte fabricado com goma tara e carragena apresentou menor firmeza quando comparado ao iogurte controle, sendo que ambos não diferiram significativamente do iogurte fabricado com goma tara. Durante o tempo de armazenamento refrigerado a firmeza dos iogurtes aumentou significativamente. Os tratamentos afetaram significativamente a pós-acidificação dos iogurtes, sendo que o iogurte controle apresentou menor pH quando comparado ao iogurte fabricado com adição de goma tara e carragena. O pH de todos os produtos diminuiu significativamente nos primeiros 8 dias de armazenamento refrigerado, mantendo-se estável após esse período / Abstract: Nowadays, the hydrocolloids addition is an applied mean to modify the texture or to avoid defects, such as syneresis, in dairy products. Hydrocolloids can be utilized as thickening, gelling and stabilizing agents, and can show synergistic features when applied along each other. The objective of this research was to evaluate the effect of addition of tara gum and carrageenan on the syneresis of non-fat set yogurt. Non-fat reconstituted milk added with carrageenan and tara gum in concentrations from 0 to 0.0585%, at combinations given by response surface methodology, was used. Composition and syneresis (spontaneous, by drainage, and by centrifugation) evaluations were done after 48 hours of cold storage. Tara gum significantly affected the syneresis, increasing it in concentrations higher than 0.0293%, independent of the type of syneresis evaluation. The effects of carrageenan and polysaccharides¿ interaction on the syneresis were not significative. The concentrations evaluated during 29 days were control yogurt (no polysaccharide addition), yogurt with 0.02% of tara gum and yogurt with 0.02% of tara gum and 0.02% of carrageenan. Composition was evaluated approximately after 24 hours. The pH (for post-acidification evaluation), spontaneous syneresis and firmness were evaluated during the cold storage at 1, 8, 15, 22 and 29 days after manufacture of yogurts. Natural syneresis was affected by the treatments and yogurt with tara gum and carrageenan showed the lowest whey-off, while the yogurt containing only tara gum showed the highest syneresis. Firmness was significantly affected by treatments. The lowest firmness was observed in yogurt containing carrageenan and tara gum, when compared to control yogurt, but both yogurts didn't differed from yogurt containing only tara gum. Yogurt firmness increased during cold storage. Regarding the post-acidification, the treatments significantly affected the pH and the control yogurt showed the lowest pH, if compared to yogurt manufactured with tara gum and carrageenan. The pH of all yogurts significantly decreased at the first eight days of cold storage, stabilizing during cold storage / Mestrado / Mestre em Tecnologia de Alimentos

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Os antiinflamatÃrios podem apresentar efeitos diferenciados quanto a eficÃcia terapÃutica, podendo, alguns serem bons analgÃsicos e outros potentes antiinflamatÃrios. Neste estudo, foram avaliados e comparados os efeitos anti-edematogÃnicos de antiinflamatÃrios nÃo esteroidais seletivos COX-2, lumiracoxibe 5mg/Kg, 30mg/Kg, 100mg/Kg, relativamente seletivos, nimesulida 25mg/Kg, meloxicam 30mg/Kg, nÃo seletivos COX, diclofenaco de sÃdio 20mg/Kg, alÃm dos glicocorticÃides dexametasona (3mg/Kg) e hidrocortisona (4mg/Kg), no clÃssico modelo de edema em pata de rato induzido por carragenina (EPICg). Cada grupo com 4 animais, recebia uma hora antes da injeÃÃo subcutÃnea (s.c) intraplantar do estÃmulo inflamatÃrio a dose referente de cada droga a ser testada, sendo que o grupo-controle recebia soluÃÃo salina 0,9%. ApÃs uma hora da administraÃÃo destas doses, 0,1mL de carragenina a 1% era injetada na pata direita de cada animal. O volume da pata edemasiada foi aferido quatro vezes em intervalos de uma hora, em um pletismÃgrafo digital (Ugo Basile Â).O efeito antiedematogÃnico de cada droga testada foi determinado pela comparaÃÃo dos resultados com o grupo-controle atravÃs do teste ANOVA. Dexametasona (3mg/Kg) e diclofenaco (20mg/Kg) foram as drogas com melhor desempenho, com taxa de reduÃÃo significativa do edema, na 3Â hora, em 94,20% e 84,43%, respectivamente. JÃ o lumiracoxibe, nas trÃs concentraÃÃes utilizadas, 5mg/Kg, 30mg/Kg, 100mg/Kg, obteve efeito significativo na reduÃÃo do edema, com 47,49%, 61,21%, 47,76% respectivamente na 3Â hora. Meloxicam, nimesulida e hidrocortisona tambÃm demonstraram eficiÃncia, com taxas de 42,48%, 62,27% e 58,84%, respectivamente. O presente estudo demonstrou que dexametasona (3mg/Kg) e diclofenaco (20mg/Kg) apresentaram potente aÃÃo antiedematogÃnica e que drogas mais seletivas COX-2 nÃo mostraram eficÃcia comparÃvel ao diclofenaco / The anti-inflammatories might present several efects about de therapeutical efficacy being some powerful antiinflammatories, but others act as excellent analgesics. In this study were observed and compared the anti-edematogenic efects of selective COX-2 non-steroidal antiinflammatories, lumiracoxib 5mg/Kg, 30mg/Kg, 100mg/Kg, relatively selected, nimesulide 25mg/Kg, meloxicam 30mg/Kg, non selective COX, diclofenac 20mg/Kg, yet of the glucocorticoids dexamethasone (3mg/Kg) and hydrocortisone (4mg/Kg), on the classic model of the edema on rat paw induced by carrageenan. Each group of four animals got one hour before the subcutaneous injection (sc) of the inflamatory estimulation the dosage of each drug to be tested, being that the control group received saline solution 0.9%. After one hour of the management of those dosages, 0.1% to 1% of carrageenan was injected in the right paw of each animal. The volume of the edema paw was checked four times in between one hour breaks, in a digital pletismograph (Ugo Basile Â).The antiedematogenic effect of each tested drug was determined by the comparission of the results with the control group through the ANOVA test. Dexamethasone (3mg/Kg) and Diclofenac (20mg/Kg) were the drugs with best performance with significative reduction rate of the edema, on the third hour, in 94.20% and 84.43% respectively. But the lumiracoxib on the three concentrations used, 5mg/Kg, 30mg/Kg, 100mg/Kg got significative effect on the reduction of the edema with 47,49%, 61,21%, 47,76% respectively on the third hour. Meloxicam, nimesulide and hydrocortisone also demonstrated eficiency with rates of 42,48%, 62,27% and 58,84% respectively. The current study demonstrated that dexamethasone (3mg/Kg) and diclofenac (20mg/Kg) presented potencial antiedematogenic action and that more COX-2 selective drugs didnât show eficacy comparable to diclofenac

Orientador: Cláudia Herrera Tambeli / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-22T19:36:40Z (GMT). No. of bitstreams: 1 Bonet_IvanJoseMagayewski_M.pdf: 8243433 bytes, checksum: a5cdaab90bdcc5bbba66a0e5e4a1293f (MD5) Previous issue date: 2013 / Resumo: O Receptor Potencial Transiente Ankiryn 1 (TRPA1) é um canal não seletivo a cátions importante na fixação do limiar nociceptivos e pertencente à superfamília de canais TRP. É expresso em fibra C-nociceptiva e células não neuronais envolvidas na liberação de mediadores pró-inflamatórios. No presente estudo, investigamos se o TRPA1 contribui para a hiperalgesia induzida pela carragenina em ratos, e se essa contribuição é mediada por mecanismos de inflamação, tais como liberação de citocinas pró-inflamatórias e migração de neutrófilos e/ou sensibilização direta do neurônio aferente primário. Avaliamos a sensibilização do nociceptor induzida pela carragenina utilizando estímulos mecânico (analgesímetro mecânico) e químico (capsaicina), com ou sem bloqueio farmacológico local do receptor TRPA1 pelo seu antagonista seletivo HC 030031. A carragenina induziu hiperalgesia com pico na terceira hora, persistindo até vigésima quarta hora. O bloqueio farmacológico do receptor TRPA1 por co-administração de HC 030031 diminuiu significativamente a hiperalgesia induzida pela carragenina na terceira hora e a pós-administração de HC 030031 (2hrs 55min) reduziu na terceira e na sexta hora. O silenciamento do gene do TRPA1, induzido por um pré-tratamento intratecal com Oligonucleotídeo antisense, preveniu a hiperalgesia induzida pela carragenina após 24 horas além de reduzir significativamente a expressão de TRPA1 em células dos gânglios da raiz dorsal (GRD) (L5-6). O tratamento com carragenina, por sua vez, não alterou a expressão do receptor TRPA1 no GRD, e tampouco afetou os níveis de citocinas e a migração de neutrófilos no tecido periférico (patas). Concluímos que TRPA1 tem papel importante no desenvolvimento e manutenção da hiperalgesia inflamatória induzida pela carragenina por contribuir diretamente na excitabilidade do nociceptor. Baseado nesses achados, sugerimos que o bloqueio de TRPA1 é uma estratégia promissora no desenvolvimento de futuras drogas para o controle e tratamento da dor / Abstract: The Transient Receptor Potential Ankiryn 1 (TRPA1) is a nonselective cation channel, important in setting nociceptive threshold belonging to the superfamily of TRP channels. It is expressed in nociceptive C-fibers and in non-neuronal cells involved in pro-inflammatory mediators release. In this study, we asked whether TRPA1 contributes to carrageenan-induced hyperalgesia in rats, and whether this contribution is mediated by mechanisms in inflammation, such as cytokine release and neutrophil migration and/or by a direct sensitization of the primary afferent nociceptors. We measured the carrageenan-induced nociceptive sensitization using a mechanical (mechanical analgesymeter) and a chemical (capsaicin) stimulus, with or without pharmacological blockade of TRPA1 by its selective antagonist HC 030031. Carrageenan-induced Hiperalgesia has peaked at the third hour and persisted until the twenty-fourth hour. Pharmacological blockade of TRPA1 receptor by co-administration of HC 030031 significantly lowered carrageenan-induced hiperalgesia at the third hour and post-administration (2hrs 55min) decreased at both third and sixth hours. The neuronal TRPA1 gene silencing induced by intrathecal pre-treatment with antisense oligodoexynucleotide completely prevented carrageenan-induced hyperalgesia over 24 hours and significantly reduced TRPA1 expression in the dorsal root ganglia cells (DRG ) (L5-6). However, carrageenan treatment, did not affect the TRPA1 expression on DRG, neither affected the cytokines levels and neutrophil migration in peripheral tissue (paws). We conclude that TRPA1 plays an important role in the development and maintenance of carrageenan-induced inflammatory hyperalgesia by directly contributing to nociceptor excitability. Based on these findings, we suggest that TRPA1 blockade is a promising strategy for the development of future drugs to pain treatment and control / Mestrado / Fisiologia / Mestre em Biologia Funcional e Molecular

Orientador: Marcelo Cristianini / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-08T00:01:13Z (GMT). No. of bitstreams: 1 Torrezan_Renata_D.pdf: 7323790 bytes, checksum: 207de2c2a0d4ced64e9eb7e22e1a3857 (MD5) Previous issue date: 2007 / Resumo: O isolado proteico de soja (IPS) é um produto com pelo menos 90% de proteínas que, devido às suas características físico-químicas, possui certas propriedades funcionais tecnológicas que influenciam a sua aceitação e utilização como ingrediente em produtos cárneos, alimentos infantis, bebidas e produtos de panificação. Os polissacarídeos, pectina e k-carragena são utilizados em alimentos como espessantes, geleificantes e estabilizantes de emulsões. Neste trabalho foram avaliados os efeitos do tratamento sob alta pressão, utilizando-se os dois tipos de equipamentos existentes no mercado: isostático e dinâmico, sobre as características funcionais tecnológicas (solubilidade e índice de atividade emulsificante - IAE) do isolado proteico de soja, como também da mistura de isolado proteico de soja com pectina e k-carragena, com o equipamento isostático. No caso do equipamento isostático, foram também analisadas as propriedades reológicas ¿ G¿ e G¿¿. Para a análise dos efeitos do tratamento sob alta pressão isostática sobre o isolado proteico de soja foi utilizado o planejamento fatorial completo (23), cujas variáveis independentes foram a concentração de proteína, pH e nível de pressão. Para o equipamento dinâmico as variáveis foram o pH e o nível de pressão aplicado. Um planejamento fatorial fracionário (24-1) foi utilizado inicialmente, para os sistemas proteína de soja¿polissacarídeos para avaliar os efeitos das variáveis independentes (concentração de isolado de soja, concentração de polissacarídeo utilizado - pectina ou k-carragena, pH e nível de pressão isostática) e posteriormente foi realizado um planejamento fatorial completo (23) fixando-se a concentração de IPS em 1%, obtendo-se as superfícies de resposta. De cada planejamento fatorial completo foram selecionados os ensaios que apresentaram as maiores respostas em cada característica funcional (solubilidade, índice de atividade emulsificante e conforme o caso, G¿) e avaliadas também o teor de sulfidrila livre, comportamento eletroforético, grau de desnaturação das proteínas (calorimetria diferencial de varredura), perfil cromatográfico e documentação da microestrutura (microscopia eletrônica de varredura). A solubilidade proteica foi fortemente influenciada pela variável pH em todas as faixas de pH estudadas, tanto quando se utilizou apenas a proteína de soja quanto da sua utilização adicionada de pectina e k-carragena, para ambos os equipamentos de alta pressão utilizados: isostático e dinâmico. Quando se trabalhou apenas com a proteína de soja, utilizando-se o equipamento de alta pressão isostática na faixa de pH mais baixa (2,66 ¿ 4,34) o valor de IAE foi máximo nos tratamentos sob baixa pressão. Na faixa de pH de 5,16 a 6,84 os valores mais altos de IAE foram obtidos na região de valores centrais de pressão e de baixo pH. Quando se adicionou pectina ou k-carragena à proteína de soja o IAE atingiu valores mais altos para os tratamentos sob pressão isostática nos pontos extremos (mais baixos ou nos mais altos). Quando se utilizou o equipamento sob alta pressão dinâmica os maiores valores de IAE estão próximos aos ponto isoelétrico da proteína de soja. Em todos os experimentos realizados no equipamento isostático o módulo de perda ou componente viscoso (G¿¿) foi o componente dominante, exibindo um comportamento predominantemente viscoso. A análise das amostras selecionadas em cada experimento com os maiores valores de solubilidade proteica, IAE e quando foi o caso G¿¿ utilizando apenas a proteína de soja ou misturas da proteína de soja com pectina ou k-carragena mostraram que o tratamento sob alta pressão isostática e dinâmica diminuíram em maior ou menor grau o teor de sulfidrila livre de todas as amostras analisadas, evidenciando uma mudança na molécula da proteína confirmada pelas alterações observadas através das análises de calorimetria diferencial de varredura, cromatografia líquida de fase reversa, eletroforese e microscopia eletrônica. Foi realizada também uma avaliação sobre os efeitos do tratamento sob alta pressão isostática (200-700 MPa) sobre os fatores antinutricionais teor de fitato e inibidor de tripsina, constatando-se que a alta pressão não alterou os teores do inibidor de tripsina; porém, não foram detectadas concentrações de fitato após este tratamento / Abstract: Soy protein isolate (SPI) contains at least 90% protein and its physics and chemical properties define some functional properties that influence its use and acceptance as an ingredient in meat products, baby foods, beverages and bread products. The polysaccharides pectin and k-carrageenan are used as a thickening, gelation and emulsion stabilising agent in some food products. The effects of isostatic and dynamic high pressure on functional properties (solubility and emulsifying activity index ¿ EAI) of SPI alone as well of SPI mixed with pectin and k-carrageenan (only for isostatic high pressure treatment) were evaluated in this work. For isostatic high pressure processing the rheological properties G¿ and G¿¿ were also evaluated. To analyse the effects of isostatic high-pressure treatment on SPI a complete factorial design 23 was applied with protein concentration, pH and pressure as independent variables. For dynamic high-pressure treatment the variables were the pH and the pressure. Initially, to analyse the effects of independent variables (protein concentration, polysaccharide concentration ¿pectin or k-carrageenan, pH and pressure level) in mixed protein-polysaccharide systems a fractional factorial design 24-1 was applied and the protein concentration was fixed at 1% for the next complete designs. The samples with the highest effect on protein solubility, EAI and in some cases also G¿¿ value were evaluated as well by electrophoresis (Native and SDS-Page), free sulphydryl determination, reversed phase high pressure liquid chromatography (RP-HPLC), differential scanning calorimetry (DSC) and having their microstructure documented. The pH was the main factor that affecting protein solubility in all studied pH ranges, for SPI alone and SPI mixed with polysaccharides and for both high-pressure equipments. The EAI was maximum in low high-pressure treatments (200-300 MPa) with isostatic equipment for pH 2.66-4.34 range, when the system was only SPI. In pH 5.16-6.84 range the highest EAI values was in middle high-pressure values (450 MPa) and low pH. When SPI was mixed with pectin and k-carrageenan the highest values of EAI was in the extreme points of isostatic high pressure (the highest or the lower). When dynamic high-pressure equipment was used the region of the highest values of EAI was near by the soy protein isoelectric point (pI). Loss modulus (G¿) was the dominant compound in all the isostatic experiments done and exhibited a predominantly viscous behaviour. The selected samples analysis with SPI alone as well SPI mixed with pectin or k-carrageenan samples showed that isostatic or dynamic high pressure treatment decreased in some degree the free sulphydryl content of all analysed samples showing that some change occurred in soy protein molecule as confirmed by DSC, RP¿HPLC, electrophoresis and scanning electronic microscopy. The evaluation of isostatic high pressure treatment (200-700 MPa) on antinutritional factors such as phytate content and trypsin inhibitor showed that high pressure did not change the trypsin inhibitor activity but was effective in eliminating the phytate content / Doutorado / Doutor em Tecnologia de Alimentos

Charles University, Faculty of Pharmacy in Hradci Králové Department of Pharmaceutical Technology Name: Martina Kišková Title of diploma thesis: Adhesive properties of matrix tablets Supervisor: PharmDr. Eva Šnejdrová, Ph.D. The diploma thesis deals with the evaluation of rheological and adhesive properties of the mucin, aqueous dispersions of polymeric carriers and matrix tablets based on chitosan and sodium alginate or iota-carrageenan loaded with the salicylic acid using absolute rotational rheometer. The theoretical part deals with the characterization and classification of matrix tablets, polymeric carriers (sodium alginate, chitosan and carrageenan) and with the principles of evaluation of rotational, adhesive and oscillational tests performed in the experimental part. The mucin from porcine gastric used as a model substrate for adhesion tests behaves as a viscoelastic solid and its adhesive strength decreases with increasing hydration. Significantly higher adhesive strength was found for chitosan at pH 1.2 and sodium alginate at pH 6.8 compared to the adhesive strength of iota-carrageenan. In terms of viscoelastic properties, chitosan and sodium alginate are viscoelastic fluids, but iota-carrageenan is a viscoelastic solid. Iota-carrageenan forms the stiffest gel after hydration at pH 6.8...

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The available literature indicates that to date, few research has been performed on oil powders for topical delivery. The aim of this project was to investigate the release characteristics of oil powder formulations, as well as their dermal and transdermal delivery properties. Whey protein-stabilised emulsions were used to develop oil powders. Whey protein was used alone, or in combination with chitosan or carrageenan. Nine oil powders, with salicylic acid as the active ingredient, were formulated by using the layer-by-layer method. Three different pH values (pH 4, 5 and 6) were used to prepare the formulations, because of the different charges that polymeric emulsifiers may have. The characteristics of the prepared oil powders were determined, including their droplet sizes, particle size distributions, loss on drying, encapsulation efficiencies, oil leakage and water dispersibility. Release studies (membrane diffusion studies) were conducted by utilising cellulose acetate membranes (0.2 μm pore size) and Franz-type diffusion cells over a period of eight hours. The release of the active ingredient was determined for all nine powders, their respective template emulsions, as well as their respective oil powders redispersed in water. The release of salicylic acid from the respective redispersed oil powders was then further compared to its release from the template emulsions and from the oil powders. The effect of pH and different polymer types used in preparing the oil powders, their respective redispersed oil powders and the template emulsions were determined with regards to the release of the active ingredient from all these preparations. The effect of pH and different polymers used was furthermore determined on the oil powders and their respective redispersed oil powders, with regards to their dermal and transdermal deliveries. Transdermal delivery and skin uptake were investigated on specifically selected powders only, based on the outcomes of the oil powder characterisation and release data. The qualifying formulations were chitosan pH 4, 5 and 6, whey and carrageenan pH 6 oil powders, together with their respective redispersed oil powders in water. Human abdominal skin was dermatomed (thickness 400 μm) for use in the diffusion studies. Franz-type diffusion cells were used over a period of 24 hours. The results of the membrane release studies indicated that the oil powders had achieved a significantly higher release than their respective redispersed oil powders. The release of salicylic acid from the redispersed oil powders and from their respective emulsions was similar. The transdermal delivery test outcomes showed that the effect of pH could have been influenced by the degree of ionisation, resulting in a decrease in permeation with increasing ionisation of salicylic acid, in accordance with the pH partition hypothesis. Furthermore, biopolymers, such as chitosan had demonstrated a penetration enhancing effect, which had led to the enhanced dermal and transdermal delivery of salicylic acid. A correlation was also found between the powder particle size and transdermal delivery. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2014

The available literature indicates that to date, few research has been performed on oil powders for topical delivery. The aim of this project was to investigate the release characteristics of oil powder formulations, as well as their dermal and transdermal delivery properties. Whey protein-stabilised emulsions were used to develop oil powders. Whey protein was used alone, or in combination with chitosan or carrageenan. Nine oil powders, with salicylic acid as the active ingredient, were formulated by using the layer-by-layer method. Three different pH values (pH 4, 5 and 6) were used to prepare the formulations, because of the different charges that polymeric emulsifiers may have. The characteristics of the prepared oil powders were determined, including their droplet sizes, particle size distributions, loss on drying, encapsulation efficiencies, oil leakage and water dispersibility. Release studies (membrane diffusion studies) were conducted by utilising cellulose acetate membranes (0.2 μm pore size) and Franz-type diffusion cells over a period of eight hours. The release of the active ingredient was determined for all nine powders, their respective template emulsions, as well as their respective oil powders redispersed in water. The release of salicylic acid from the respective redispersed oil powders was then further compared to its release from the template emulsions and from the oil powders. The effect of pH and different polymer types used in preparing the oil powders, their respective redispersed oil powders and the template emulsions were determined with regards to the release of the active ingredient from all these preparations. The effect of pH and different polymers used was furthermore determined on the oil powders and their respective redispersed oil powders, with regards to their dermal and transdermal deliveries. Transdermal delivery and skin uptake were investigated on specifically selected powders only, based on the outcomes of the oil powder characterisation and release data. The qualifying formulations were chitosan pH 4, 5 and 6, whey and carrageenan pH 6 oil powders, together with their respective redispersed oil powders in water. Human abdominal skin was dermatomed (thickness 400 μm) for use in the diffusion studies. Franz-type diffusion cells were used over a period of 24 hours. The results of the membrane release studies indicated that the oil powders had achieved a significantly higher release than their respective redispersed oil powders. The release of salicylic acid from the redispersed oil powders and from their respective emulsions was similar. The transdermal delivery test outcomes showed that the effect of pH could have been influenced by the degree of ionisation, resulting in a decrease in permeation with increasing ionisation of salicylic acid, in accordance with the pH partition hypothesis. Furthermore, biopolymers, such as chitosan had demonstrated a penetration enhancing effect, which had led to the enhanced dermal and transdermal delivery of salicylic acid. A correlation was also found between the powder particle size and transdermal delivery. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2014

The endogenous cannabinoids (endocannabinoids) anandamide (AEA) and 2-arachidonylglycerol (2-AG) exert their effects predominantly through cannabinoid CB1 and CB2 receptors, but these actions are short-lived because of rapid hydrolysis by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. Selective inhibition of either enzyme elevates CNS levels of the appropriate endocannabinoid and produces analgesic effects with fewer psychomimetic side effects than Δ9-tetrahydrocannabinol (THC), the primary active constituent of marijuana. While cannabinoid receptor agonists and FAAH inhibitors reliably produce anti-inflammatory and anti-hyperalgesic effects in the carrageenan test and other inflammatory pain models, much less is known about the consequences of inhibiting MAGL in these assays. Here, we tested whether the selective MAGL inhibitor JZL184 would reduce nociceptive behavior in the carrageenan test. JZL184 significantly attenuated carrageenan-induced paw edema and mechanical allodynia, whether administered before or after carrageenan. Complementary genetic and pharmacological approaches revealed that JZL184’s anti-allodynic effects required both CB1 and CB2 receptors, but only CB2 receptors mediated its anti-edematous actions. Importantly, the anti-edematous and anti-allodynic effects of JZL184 underwent tolerance following repeated injections of high dose JZL184 (16 or 40 mg/kg), but repeated administration of low dose JZL184 (4 mg/kg) retained efficacy. Interestingly, the anti-allodynic effects of the combination of low dose of JZL184 (4mg/kg) and high dose of the selective and long-acting FAAH inhibitor PF-3845 (10 mg/kg) was augmented compared with each drug alone. On the contrary, the combination treatment did not reduce edema more than either JZL184 or PR-3845 given alone. These results suggest that low doses of MAGL inhibitors alone or in combination with FAAH inhibitors, reduce inflammatory nociception through the activation of both CB1 and CB2 receptors with no evidence of tolerance following repeated administration.

A hiperalgesia inflamatória é o processo pelo qual ocorre a sensibilização dos neurônios nociceptores aferentes primários por mediadores químicos inflamatórios, gerando assim uma diminuição do limiar nociceptivo e como consequência episódios de dor. Entre os principais mediadores envolvidos com a sensibilizacão das fibras nociceptivas periféricas está a prostaglandina E2 (PGE2), que é liberada como um produto final de uma cascata de mediadores inflamatórios. Dentro desta cascata de liberação hierárquica podemos destacar a interleucina -1? (IL)-1?, uma citocina importante na gênese da dor inflamatória, devido à sua capacidade de induzir a produção da enzima cicloxigenase-2 (COX-2), e consequentemente PGE2. O mecanismo de controle da produção da IL-1 ? envolvem dois passos intracelulares: a indução da expressão de uma forma protêica inativa (a pró-IL-1 ?) e a geração da forma biologicamente ativa (IL-1?) a partir da pró-IL-1 ?. Este último passo envolve a ação de uma cisteína-protease ativada em decorrência de um processo inflamatório, conhecida como Caspase-1, a qual cliva a pró-IL-1? em IL1?. Recentemente, nosso grupo demonstrou que a caspase-1 tem um papel importante na gênese da dor inflamatória, sendo crucial para a geração de IL-1? e consequentemente COX2/PGE2. Porém, não são conhecidos os mecanismos de ativação da caspase-1 na hiperalgesia inflamatória. Sabe-se que a ativação da Caspase-1 e clivagem da pro-IL-1? são dependentes de uma plataforma molecular intracelular denominada inflamassoma. Os principais inflamassomas ativadores de caspase-1 são formados pelas proteínas NLRP3, IPAF (NLRC4) e por sua molécula adaptadora ASC. O objetivo desse trabalho então foi avaliar a participação do inflamassoma na gênese da dor inflamatória. Nós identificamos que as moléculas IPAF e ASC, mas não o NLRP3, participa no desenvolvimento da hiperalgesia inflamatória mecânica e térmica induzida pela carragenina. Observou-se que estas moléculas são cruciais para a ativação da Caspase-1 e, consequentemente, para a produção da IL-1? ativa. Estes resultados evidenciam pela primeira vez um papel importante do inflamassoma no desenvolvimento da hiperalgesia inflamatória. / The inflammatory hyperalgesic is the process by which occurs the sensitization of nociceptors primary afferent neurons by inflammatory chemical mediators, that generating a decreased nociceptive threshold and result in episodes of pain. Among the main of nociceptive mediators involved with sensitization of peripheral nociceptive fibers are prostaglandin E2 (PGE2), which is released as a final product of a cascade of inflammatory mediators. Within this hierarchical cascade of release can highlight interleukin-1? (IL)-1?, a cytokine important in the genesis of inflammatory pain due to their ability to induce the production of the enzyme cyclooxygenase-2 (COX-2) and consequently PGE2. The control mechanism production of intracellular IL-1 ? involved two steps: induction of expression of a protein inactive form (pro-IL-1 ?) and the generation of the biologically active form from pro-IL-1 ? (IL-1?). This last step involves the action of a cysteine protease-activated due to an inflammatory process, known as Caspase-1, which cleaves pro-IL-1? to IL-1?. Recently our group has demonstrated that caspase-1 plays an important role in the genesis of inflammatory pain, crucial for the generation of IL-1? and consequently COX2/PGE2. However, there aren\'t known mechanisms of activation of caspase-1 in inflammatory hyperalgesic. It is known that the activation of Caspase-1 cleavage and pro-IL-1? are dependent on an intracellular molecular platform called inflammassome. The main inflammassome activators of caspase-1 proteins are formed by NLRP3, IPAF (NLRC4) and its adapter molecule ASC. The aim of this study was to evaluate the inflammassome participation in the genesis of inflammatory pain. We have identified molecules IPAF and ASC, but not NLRP3, is participate in the development of mechanical and thermal inflammatory hyperalgesic induced by carrageenan. It was observed that these molecules are crucial for the activation of Caspase-1 and thus for the production of active IL-1?. These results demonstrate for the first time an important role of the inflammassome in the development of inflammatory hyperalgesic.