Les polymères présentant des liens phosphoesters dans leur squelette sont biodégradables et constituent une classe émergente de nouveaux biomatériaux, utiles notamment dans le domaine de la délivrance de médicaments. La pentavalence du phosphore offre de nombreuses possibilités d’en varier la structure ce qui permet d’envisager une gamme diversifiée de propriétés pour ces matériaux.Cette thèse envisage la synthèse et l’utilisation de nouveaux copolymères biséquencés de polyoxyde d’éthylène et de polyphosphotriester portant des insaturations pendantes comme plateforme pour l’élaboration de systèmes de délivrance avancés. D’une part, l’auto-assemblage en milieu aqueux de copolymères amphiphiles porteurs de groupes butènyles permet l’obtention de micelles à coeur réticulé dans lesquelles la doxorubicine peut être incorporée par imprégnation. Ces nanovecteurs micellaires montrent une stabilité et un taux d’encapsulation supérieurs aux systèmes non réticulés correspondants.D’autre part, des copolymères porteurs de groupes alcynyl ou allyl pendants sont convertis en copolymères doublement hydrophiles capables de complexer le calcium. Utilisés comme agent structurant pour la formation de particules de carbonate de calcium, ceux-ci permettent d’en réduire la taille et son hétérogénéité de façon remarquable. Le recours à un procédé utilisant le dioxyde de carbone à l’état supercritique conduit ainsi à des particules de 1.5μm.Enfin, l’ajout de lysozyme à ce procédé permet son encapsulation dans les particules de CaCO3, en préservant l’activité de cette protéine plus efficacement que le procédé conventionnel recourant à l’acide hyaluronique. / Polymers with repeating phosphoester linkages in the backbone are biodegradable and emerged as a promising class of novel biomaterials, especially in the field of drug delivery systems. The pentavalency of the phosphorus atom offers a large diversity of structures and as a consequence a wide range of properties for these materials.The thesis focused on the synthesis of novel well-defined diblock copolymers made of one hydrophilic polyethylene oxide (PEO) block and one polyphosphotriester (PPE) block bearing unsaturations as side-group, as a platform for the design of advanced drug delivery systems.Firstly, novel alkenyl PEO-b-PPE amphiphilic copolymers were self-assembled in water, taking profit of the unsaturations to prepare core cross-linked micelles. Doxorubicin could be successfully loaded by impregnation in these micellar nanocarriers leading to improved stability and loading as compared to the corresponding non-cross-linked systems.Besides, the alkynyl and allyl unsaturations of PEO-b-PPE copolymers were used to prepare novel double hydrophilic block copolymers exhibiting calcium complexation capabilities. They were found quite efficient as template for the formation of calcium carbonate particles providing particles of unprecedented small size, and high size homogeneity. The use of a supercritical carbon dioxide process with carboxylic acid containing copolymers allows reaching CaCO3 particles about 1.5 μm. Finally, we demonstrate that adding lysozyme to the process allows encapsulation of this enzyme into the CaCO3 carriers, the protein activity being better preserved by using the PPE-b-PEO as compared to more conventional hyaluronic acid as a template.

O objetivo deste estudo clínico foi avaliar a eficácia clínica de um dispositivo polimérico celulósico carregado com sal anestésico, na prevenção da dor pré-procedimento operatório em odontologia, diminuindo ou eliminando o uso de agulhas gengivais em anestesias infiltrativas. Foram testados três dispositivos com propriedade bioadesiva para a liberação modificada de fármacos em contato com a mucosa oral, um contendo um núcleo central de prilocaína e lidocaína em iguais concentrações e um contendo somente lidocaína, a liberação dos princípios ativos se deu pelo processo de fast-dissolve, e o terceiro constituído somente pelo sistema bioadesivo, sem qualquer sal anestésico(controle negativo), em desenho pareado. Os dispositivos foram aplicados na região do fórnice do vestíbulo dos pré-molares superiores, após limpeza e secagem superficial da mucosa. Foram selecionados 21 voluntários de ambos os gêneros, normotipos, saudáveis, com faixa etária entre 18 e 30 anos, para um teste clínico randomizado, controlado, crossover e triplo-cego. O teste de sintomatologia pré e pós-aplicação foi realizado com o emprego da sonda computadorizada Florida Probe® System, (Florida Probe Corporation, Gainesville, FL, USA), aplicada no sentido perpendicular ao tecido mucoso, simulando o uso de agulha gengival e com pressão constante de 25 gramas, já calibrada pelo próprio sistema, foi aplicado também o teste térmico com o uso de Endo-Frost® Roeko para verificação da profundidade anestésica em nível pulpar. Para a mensuração da sintomatologia dolorosa presente/ausente foi utilizada escala visual analógica (EVA) e a versão em Língua Portuguesa do McGill Pain Questionnaire. Os indivíduos receberam instruções de como responder aos questionários para mensuração dos estímulos dolorosos, que foram computados imediatamente após a resposta. Os resultados obtidos demonstraram uma eficiência anestésica favorável para os dois dispositivos carregados com os sais onde não houve diferença estatística quanto ao efeito, porém na relação efeito versus tempo o dispositivo com os dois sais apresentou melhor resultado para o teste térmico. Conclui-se que ambos os dispositivos (B e C) apresentaram efeito anestésico tanto tópico quanto em profundidade pela diminuição da dor provocada pelos dois testes (mecânico/térmico) propostos. / The objective of this clinical study was to evaluate the efficacy of a cellulosic polymer dispositive loaded with anesthetic salt to prevent pain in dentistry pre-operative procedure, reducing or eliminating the use of gingival needles in infiltrative anesthesia. Three dispositives were tested with bioadhesive property for drugs delivery system in contact with the oral mucosa, containing prilocaine and lidocaine at same concentrations, and other containing just lidocaine with release of active elements through the process of fast-dissolve, and the other only the same bioadhesive system, without the active (negative control), paired study, which was applied in the region of the superior premolars, the mucosal surface after cleaning. Were selected 21 volunteers of both genders, normotype, healthy, aged between 18 and 30 years for a clinical trial, randomized, controlled, crossover and triple-blind. The test of symptoms before and after application was made using the electronic probe Florida Probe System® (Florida Probe Corporation, Gainesville, FL, USA), applied perpendicularly to the mucosal tissue, simulating the use of gingival needle a constant pressure of 25 grams, already calibrated by the system itself. Additional thermal testing will be proved employing Endo-Frost® tester. For the measurement of pain symptoms present / absent was used a visual analog scale (VAS) and the Portuguese language version of the McGill Pain Questionnaire adapted by Varolli and Pedrazzi (2006), using an appendix to the questionnaire (Group 9 table 1). Individuals have received instructions on how to answer the questionnaire for the measurement of painful stimuli, which would be counted immediately after the response. The results demonstrated a favorable anesthetic efficiency for both dispositive loaded with salts where there was no statistical difference in the effect, but for the relationship effect versus time the dispositive with two salts showed better results. It can be concluded that both devices (B and C) presented as both topical and depth anesthetic by decreasing the pain caused by the two mechanical/thermal proposed tests.

In Thailand, Acanthus ebracteatus Vahl and Clerodendrum petasites S. Moore have been prescribed to treat skin diseases, such as rash, abscess, and urticaria, for at least 30 years. However, there is limited scientific support and no clinical trials that identify and verify the compounds that elicit useful pharmacological effects following their topical delivery. Vanillic acid was identified for the first time in A. ebracteatus together with verbascoside; furthermore, nine phenolic compounds, vanillic acid, 4-coumaric acid, ferulic acid, verbascoside, nepetin, luteolin, chrysin, naringenin, and hesperetin, and two reported, apigenin and hispidulin, were found in C. petasites. C. petasites (CP) was therefore chosen as the principal plant to be studied in this thesis. Hispidulin was quantified as a predominant compound, being present at 39 μmol/g (1.2% w/w) in a dried ethanolic extract. Various formulations of CP extracts were examined (a) in in vitro skin penetration experiments using Franz diffusion cells, and (b) in vivo using the tape-stripping method. Hispidulin penetrated through the skin within 3 hours; vanillic acid and nepetin were absorbed after 6 hours. In contrast, verbascoside was only taken up into the superficial layers of SC. There was no difference in the permeation of hispidulin, nepetin and vanillic acid from 10% w/w CP cream and lotion formulations. Hispidulin was percutaneously absorbed through the skin and taken up into the stratum corneum in the greatest amount, followed by vanillic acid and nepetin. It was found that the in vitro model was useful for preliminary formulation development, and that the tape-stripping method was robust and effective. Verbascoside, although a poor penetrant, was well released from the formulations in an in vitro release test, suggesting that it might be a potential skin surface-active compound, such as an antimicrobial. Hispidulin, nepetin and vanillic acid, based on their uptake and penetration into the skin, together with their known biological activities, may be considered as feasible candidates for the development of novel and effective antimicrobial, anti-inflammatory, and antioxidant formulations.

This thesis examines the operational delivery systems of information-centric Mass Claims Processes. Empirical data is presented which builds upon existing literature within the Operations Management discipline. This thesis aims to extend the area of knowledge which focuses on the rendering of assistance to very large groups of individuals disadvantaged through particular events such as armed conflict, civil unrest, acts of government and other similarly sweeping actions. One such approach of aid delivery is through a legal process known as a Mass Claims Process which delivers assistance. This research examines how this assistance is rendered to the individual, the ‘claimant’, through a legally guided and controlled analysis of claimant-provided information. Such organisations are typically either publicly funded or funded through social schemes, which introduces significant pressure for efficiency. Similarly, the legal nature of MCPs emphasises the need for accuracy in the delivery of justice and law. The research addresses a number of areas not fully explored by the extant literature. There is a lack of research which explores the apparent trade-off between efficiency and accuracy in large scale legal services. Little empirical evidence exists on the application of Postponement strategies in information-centric operations. This research also investigates a previously unexplored context in which strategic frameworks must find optimal alignment between the service concept and the design of the delivery system in a restricted and challenging environment. Fieldwork was carried out over a three year period in two separate organisations, and utilised a polar case approach to increase the validity of the findings. The phenomenon of information interrelation, previously unidentified in the literature, is shown to have significant impact in this context. Several models are presented to describe the dynamic relationships between the characteristics and the strategic choices of the MCP. The results produce a set of findings illustrating optimal design choices for the key delivery system characteristics associated with MCPs. The financial impact of such organisations reaches into the billions (USD), and will continue to be a significant economic consideration for the foreseeable future. As such, research in this area has the ability to increase the efficient use of organisational resources for the organisations, while improving the service for the applicants. Whilst this thesis contributes to the body of knowledge for delivery system design, further research is welcomed, especially on the phenomenon of information interrelation, for the growing area of information-centric organisations.

A ortopedia e a odontologia têm especial interesse às tecnologias biocompatíveis que apresentam a fase alfa do fosfato tricálcico (α-TCP), pois estas são capazes de formar hidroxiapatita deficiente em cálcio, similar à óssea. Porém, a baixa resistência mecânica limita sua aplicação. A fim de superar essa limitação, foi agregada acrilamida ao cimento α-TCP, com redutor de líquido, originando o cimento α-TCP de dupla pega. A partir disso foram desenvolvidos compostos à base de cimento de α-TCP e α-TCP de dupla pega agregados dos fármacos sulfato de gentamicina, cloridratos de lidocaína, bupivacaína e levobupivacaína e testada sua funcionalidade como sistemas de liberação de fármacos. Não existem dados bibliográficos sobre liberação de fármacos por sistemas de cimento α-TCP de dupla pega. A metodologia utilizada foi qualiquantitativa. Para as diferenças analíticas considerou-se o intervalo de confiança de 95% com nível de significância menor que 5% (p<0,05). O estudo compreendeu três fases. Na Fase 1 foram elaborados corpos de prova à base de cimento α-TCP e α-TCP de dupla pega com e sem (grupo-controle) adição de fármacos. Na Fase 2 os biomateriais estudados foram caracterizados por difração de raios X, espectroscopia de absorção no infravermelho com transformada de Fourier, microscopia eletrônica de varredura, resistência mecânica a compressão axial, densidade, porosidade e absorção de líquido; sendo também proposta a análise da porosidade por meio de imagens. A Fase 3 corresponde ao estudo da cinética da liberação dos fármacos in vitro, onde os corpos de prova foram imersos em solução tampão fosfato pH 7,0 e as amostras analisadas por meio de UV-vis. A liberação do antibiótico também foi avaliada por Espectroscopia de Impedância Eletroquímica (EIS), como proposta inovadora. Conforme os resultados, ambos os cimentos funcionaram como sistemas de liberação dos fármacos. Tanto o sistema hidrogel, quanto os fármacos não modificaram as propriedades estruturais do cimento. O sistema com hidrogel apresentou melhor resistência mecânica. A difusão Fickiana foi o principal mecanismo envolvido no processo de liberação dos fármacos, com menor influência do relaxamento das cadeias. A técnica de EIS mostrou-se promissora para avaliação de liberação de fármacos. / To better regulate it is necessary to know the new Technologies. Orthopedics and dentistry have demonstrated special interest in biocompatible technologies that present the alpha phase of tricalcium phosphate (α-TCP), whit can form calcium-deficient hydroxyapatite (like bone hydroxyapatite). However, its application is limited by the low mechanical resistance. To overcome this limitation, acrylic hydrogel containing liquid reducer was added to the α-TCP cement, resulting in the α-TCP double setting cement. From this, composites of α-TCP and α-TCP double setting cements aggregates of the drugs gentamicin sulfate, lidocaine, bupivacaine and levobupivacaine hydrochlorides were developed and the functionality drug delivery systems was tested. There isn't bibliographic data about drugs release systems by α-TCP double setting cement. Qualitative and quantitative methodologies were applied. For the analytical differences, we considered the 95% confidence interval with a level of significance lower than 5% (p <0.05). It comprised three different phases. In Phase 1, an α-TCP and α-TCP double setting cement specimens were prepared with and without (control group) drugs addition. In Phase 2, the studied biomaterials were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, compression mechanical resistance, density, porosity and liquid absorption, being also proposed of the porosity analysis by images. The Phase 3 corresponds to the study of the in vitro drug release kinetics. The specimens were immersed in phosphate buffer solution pH 7.0 and the samples analyzed by UV-vis. As an innovative proposal, drug release was also assessed using Electrochemical Impedance Spectroscopy (EIS). According to the results, both cements functioned as controlled drug delivery systems. The hydrogel improved the properties of cement moreover the drugs did not impair these properties. Fick diffusion was the main mechanism involved in the process of drug release by composites, with a minor influence of polymer chain relaxation. The EIS technique proved to be promising for the evaluation of drug release.

O objetivo deste estudo clínico foi avaliar a eficácia clínica de um dispositivo polimérico celulósico carregado com sal anestésico, na prevenção da dor pré-procedimento operatório em odontologia, diminuindo ou eliminando o uso de agulhas gengivais em anestesias infiltrativas. Foram testados três dispositivos com propriedade bioadesiva para a liberação modificada de fármacos em contato com a mucosa oral, um contendo um núcleo central de prilocaína e lidocaína em iguais concentrações e um contendo somente lidocaína, a liberação dos princípios ativos se deu pelo processo de fast-dissolve, e o terceiro constituído somente pelo sistema bioadesivo, sem qualquer sal anestésico(controle negativo), em desenho pareado. Os dispositivos foram aplicados na região do fórnice do vestíbulo dos pré-molares superiores, após limpeza e secagem superficial da mucosa. Foram selecionados 21 voluntários de ambos os gêneros, normotipos, saudáveis, com faixa etária entre 18 e 30 anos, para um teste clínico randomizado, controlado, crossover e triplo-cego. O teste de sintomatologia pré e pós-aplicação foi realizado com o emprego da sonda computadorizada Florida Probe® System, (Florida Probe Corporation, Gainesville, FL, USA), aplicada no sentido perpendicular ao tecido mucoso, simulando o uso de agulha gengival e com pressão constante de 25 gramas, já calibrada pelo próprio sistema, foi aplicado também o teste térmico com o uso de Endo-Frost® Roeko para verificação da profundidade anestésica em nível pulpar. Para a mensuração da sintomatologia dolorosa presente/ausente foi utilizada escala visual analógica (EVA) e a versão em Língua Portuguesa do McGill Pain Questionnaire. Os indivíduos receberam instruções de como responder aos questionários para mensuração dos estímulos dolorosos, que foram computados imediatamente após a resposta. Os resultados obtidos demonstraram uma eficiência anestésica favorável para os dois dispositivos carregados com os sais onde não houve diferença estatística quanto ao efeito, porém na relação efeito versus tempo o dispositivo com os dois sais apresentou melhor resultado para o teste térmico. Conclui-se que ambos os dispositivos (B e C) apresentaram efeito anestésico tanto tópico quanto em profundidade pela diminuição da dor provocada pelos dois testes (mecânico/térmico) propostos. / The objective of this clinical study was to evaluate the efficacy of a cellulosic polymer dispositive loaded with anesthetic salt to prevent pain in dentistry pre-operative procedure, reducing or eliminating the use of gingival needles in infiltrative anesthesia. Three dispositives were tested with bioadhesive property for drugs delivery system in contact with the oral mucosa, containing prilocaine and lidocaine at same concentrations, and other containing just lidocaine with release of active elements through the process of fast-dissolve, and the other only the same bioadhesive system, without the active (negative control), paired study, which was applied in the region of the superior premolars, the mucosal surface after cleaning. Were selected 21 volunteers of both genders, normotype, healthy, aged between 18 and 30 years for a clinical trial, randomized, controlled, crossover and triple-blind. The test of symptoms before and after application was made using the electronic probe Florida Probe System® (Florida Probe Corporation, Gainesville, FL, USA), applied perpendicularly to the mucosal tissue, simulating the use of gingival needle a constant pressure of 25 grams, already calibrated by the system itself. Additional thermal testing will be proved employing Endo-Frost® tester. For the measurement of pain symptoms present / absent was used a visual analog scale (VAS) and the Portuguese language version of the McGill Pain Questionnaire adapted by Varolli and Pedrazzi (2006), using an appendix to the questionnaire (Group 9 table 1). Individuals have received instructions on how to answer the questionnaire for the measurement of painful stimuli, which would be counted immediately after the response. The results demonstrated a favorable anesthetic efficiency for both dispositive loaded with salts where there was no statistical difference in the effect, but for the relationship effect versus time the dispositive with two salts showed better results. It can be concluded that both devices (B and C) presented as both topical and depth anesthetic by decreasing the pain caused by the two mechanical/thermal proposed tests.

Milk derived ingredients from the production of cheese and butter can be used as vehicles for nutrients. Buttermilk is a nutritious product of milk that comes from the churning of cream into butter. One of the advantages of buttermilk is that it is enriched in milk fat globule components, such as phospholipids and forms emulsions with fat when treated with high shear. The objective of this work was to explore the effects of shear on regular buttermilk and whey buttermilk in terms of liposomal aggregate size and chemical composition. The effects of microfluidization at 2000 psi and homogenization at 2000 psi/500 psi on the particle size distribution of liposomal aggregates between whey buttermilk (WBM) at pH 4.6 and 6.8 and commercial sweet buttermilk (SBM) at pH 4.60 were compared with whey protein isolate (WPI) at pH 4.6. At pH 6.80, WPI and SBM are too soluble in water to measure particle size but WBM is not as soluble. From this investigation, the mean particle diameter of the SBM aggregates at pH 4.6 decreased after the first pass through the microfluidizer and the same is true, after homogenization. SBM aggregates at pH 4.6 had a significantly larger mean particle diameter before treatments in both shear processes compared to WPI at pH 4.6 and WBM at pH 4.6 and WBM at pH 6.8 (p < 0.0001). WPI at pH 4.6 and WBM at both pH showed no significant differences in their mean particle size in both homogenized and microfluidized treatments. WPI and SBM samples resulted in significant particle diameter differences vi from before to after homogenizing at pH 4.6. SBM at pH 4.6 had significantly larger average particle diameter than WBM at pH 4.6 (p < 0.0002), WPI at pH 4.6 (p < 0.0002) and WBM at pH 6.8 (p < 0.0045) before microfluidization at pass 0. WBM and WPI across all treatments showed very similar tendencies in small particle size attributes and some similarities in protein composition. In addition, the small aggregate size of WBM is suggested to be influenced by the presence of phospholipids and thus, creating significantly smaller mean particles compared to SBM even before inducing high shear. In contrast, treated and untreated SBM differed from WBM in phospholipid composition in both homogenization and microfluidization techniques. WBM samples contained more phospholipids than SBM, whereas WPI samples contained very low concentrations of phospholipids. Through HPLC analysis, WPI, SBM, and WBM showed different profiling of the phospholipid classes. These differences may be due structural changes of the aggregates from shearing, initial thermal treatments or hydrophobic and/or protein-phospholipid interactions between the aggregates. SBM samples also exhibited different protein profiling than WBM and WPI samples. This study suggests that high shear and presence of phospholipids impact the size distribution of liposomal aggregates through structural alterations. The aggregates can be utilized as a novel ingredient and in the processing of dairy foods to deliver nutrition.

The performance of the century-old irrigation system of Pakistan (i.e. warabandi) has been evaluated using socio-economic data gathered by the author in multiple farmers?? surveys (n=278) conducted in Indus Basin of Pakistan. In the surveyed regions, the warabandi system was performing poorly. In-built rigidity in water allocations was found as main reason behind its poor performance. The results from the farmers?? surveys also revealed that the objective of increasing irrigation water productivity would never be attained under the warabandi arrangements. Hence, a completely new concept that could replace the warabandi system and improve the productivity of limited irrigation water should be introduced. My aim was to find a better way to allocate the scarce water resource between farmers. In this study, I have introduced a new concept for determining water allocations among the farmers, which is based on a multicriterion decision making (MCDM) approach. The consideration of multiple criteria in irrigation water allocations would improve irrigation water productivity. Upon an extensive survey of well-known MCDM methods, I concluded that all previously existing MCDM methods were using subjective inputs, usually from a single modeller, to establish priorities of alternatives and therefore, a predetermined solution could easily be obtained. I have developed an approach based on conjoint analysis which removes that subjectivity from the chosen MCDM method (i.e. ELECTRE). Interval scales and relative importance criteria weights, two usually subjective inputs in ELECTRE, are objectively estimated from the conjoint analysis study. For that purpose, the author designed a conjoint questionnaire and administered it to 62 farmer respondents in face-to-face interviews. Conjoint analysis, which does not appear to have been previously used in water resources or allocation studies, is a method for creating the interval scales and the relative criteria weights objectively from the respondents?? judgements on the importance of conjoint objects. The objective estimation of these two important factors is a completely new development which can assist in the unbiased determination of the best division or allocation of scarce water resources between farmers. The approach is applied, as a demonstration, to a region with nine distributary watercourses to determine which of the distributaries should have the highest priority for allocation of the regional water.

Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2008.

BACKGROUND Because the medical envirement continously progresses, all the people working in hospital or health department are concerned in the health issues. Although the Intergration Delivery System was used for management of respiratory care, but the medical quality still was suspected. Therefore, this study discusses what are the significantly related factors of plan or unplan extubation to elevate the quality of respiratory care. PURPOSE The purposes of this study are described bellow¡G 1.To predict the related factors of successful plan extubation. 2.To find the related factors of unplan extubation. 3.To discuss what are the causes of intubation. 4.To find the stand procedure of clinical path-way of ventilator weaning. MATERIAL This study collected data of ICU patient been used ventilator from october 2000 to october 2001. The method of analysis included Descriptive stastic analysis, Correlation, ANOVA, Stepwise regression, and Logistic regression. The data included characteristics of patient, clinical sign, ventilator setting, and the count of intubation days. RESULT 1.The plan extubation of conscious-clear patient is more successful than concious-unclear. 2.The successful extubation of CPPV mode is less than others. 3.Gender is a related factor of unplan extubation. 4.CO2 is postive correction with unplan extubation. 5.PSV mode is negative correction with unplan extubation. 6.CPPV mode is postive correction with unplan extubation. 7.Unplan extubation easily occurs in the early stage of intubation when the patient is unstable.