Ce travail étudie les matériaux composites zéolithes surfactifs, principes actifs pour des applications pharmaceutiques. D'abord sont identifiées les principales propriétés physiques, chimiques et biologiques des matériaux, requises pour des applications en tant que supports médicamenteux ciblant certaines formes de cancer. Par la suite sont décrits les différentes étapes de formulation des supports médicamenteux à base des zéolithes naturelles, les caractéristiques des matériaux intermédiaires ainsi obtenus, ainsi que les mécanismes des phénomènes interfaciaux à l'origine de l'action de ces matériaux. La dernière partie est consacrée à l'étude d'un relargage contrôlé des principes actifs de l'interface jusque dans un milieu aqueux modèle. / This work studies the composite zeolites surfactants, active principles for pharmaceutical applications. First identified the main physical, chemical and biological materials, required for applications as drug carriers targeting some cancers. Subsequently described the various stages of formulation of drug carriers based on natural zeolites, the characteristics of intermediate materials obtained, and the mechanisms of interfacial phenomena at the origin of the action of these materials. The last part is devoted to the study of controlled release of active ingredients of the interface into a model aqueous medium.

Parmi les nombreux pathogènes fongiques susceptibles d’infecter les épis de maïs, les espèces appartenant au genre Fusarium sont particulièrement préoccupantes pour la filière maïsicole. La fusariose est susceptible d’induire des pertes de rendement considérables et est fréquemment associée à une contamination des épis par des mycotoxines. Un des leviers prometteur repose sur la sélection génétique de plantes résistantes à Fusarium et à l’accumulation de mycotoxines. Plusieurs Quantitative Trait Loci (QTL) ont été identifiés d’après la caractérisation moléculaire de la résistance à la fusariose chez le maïs. Cependant malgré les progrès des approches génétiques, les mécanismes moléculaires impliqués restent en grande partie inconnus. L’identification de métabolites majeurs associés à la résistance reste donc indispensable pour la création d’un outil d’aide à la sélection variétale. Une approche métabolomique combinant de la spectrométrie de masse et de la 1H-RMN a été mise au point pour identifier un ensemble de métabolites de défense, constitutifs ou induits par l’infection, susceptibles d’intervenir dans la résistance à Fusarium. Cette approche a été appliquée aux grains à deux stades de développement sur 20 variétés présentant des degrés de résistance contrastés inoculés ou non avec une souche de Fusarium graminearum toxinogène par le canal des soies. Les résultats obtenus mettent en évidence un panel de métabolites liés à la résistance ou la sensibilité des variétés de maïs. / Fusarium graminearum is the main causal agent of maize ear rot or Gibberella ear rot (GER), an important fungal disease affecting maize. GER leads to significant economic loss and serious health issues due to the ability of F. graminearum to produce mycotoxins such as type B trichothecenes. One promising approach to control Giberella Ear Rot and reduce mycotoxins contamination is to promote host-genetic resistance. Several Quantitative Trait Loci (QTLs) have been identified in maize. However molecular basis to resistance to Fusarium infection remains largely unknown and the success of selection for GER resistance is still challenging. Biochemical approaches can provide valuable insights in the mechanisms crops employ against F. graminearum and its production of mycotoxins. A biochemical profiling could actually be an efficient way to decipher plant-pathogen interactions and progress in screening resistant maize lines. This study aims to elucidate the metabolic profiling of F. graminearum resistance and toxin accumulation in kernels toward the combination of high resolution mass spectrometry and 1H NMR to identify a large set of metabolites, preformed, constitutive as well as inducible defense metabolites that could play a key role in GER resistance. This approach was applied to kernels harvested at two developmental stages. Twenty genotypes with contrasting levels of resistance were inoculated, or not, with a toxigenic Fusarium graminearum strain through the silk channel. The obtained data allowed highlighting a set of biochemical compounds linked to the resistance or susceptibility of maize genotypes

Com o intuito de promover proteção de amplo espectro, na maioria dos protetores solares estão associados pelo menos dois filtros orgânicos (UVA e UVB). A combinação da avobenzona (BMBM), filtro UVA, e do p--metoxicinamato de octila (EHMC), filtro UVB, é conhecida e muito utilizada em formulações manipulas e industrializadas, porém apresenta alteração na absorção espectral após exposição à radiação UV. A estratégia empregada com maior frequência para reduzir a instabilidade da combinação é baseada na adição de agentes fotoestabilizadores. A adição de substâncias naturais em formulações fotoprotetoras vem sendo explorada, especialmente o grupo dos flavonoides, como a rutina, que apresenta resultados positivos em relação à eficácia fotoprotetora. O objetivo principal desta pesquisa foi avaliar o potencial da rutina como substância fotoestabilizadora dos filtros EHMC e BMBM. Foram desenvolvidas formulações contendo os dois filtros associados ou não com rutina de acordo planejamento fatorial em três níveis. As formulações foram avaliadas quanto a eficácia fotoprotetora in vitro aplicadas em placas de PMMA e analisadas por espectrofotometria de refletância com esfera de integração antes e após a exposição à radiação UV. As interações moleculares dos filtros com a rutina foram avaliadas por 1H RMN, DSC, TG e análise qualitativa da supressão do estado energético singleto. A adição de rutina nas formulações contendo 5,0% (p/p) de BMBM e 10,0% (p/p) de EHMC promoveu elevação na conservação do FPS in vitro de 53,9% para 65,8 (0,1% de rutina) e 70,8% (1,0% de rutina). As curvas DSC e TG da rutina apresentaram alterações promovidas pela presença dos filtros BMBM e EHMC, indicando interação entre o flavonoide e os filtros. Após dose de 5760 J cm-2 de radiação UV o valor da razão trans/cis para o filtro EHMC em solução adicionado do filtro BMBM foi elevado de 5,5±0,1, sem adição de rutina, para 12,6±0,4, com adição da rutina. A análise qualitativa da supressão do estado singleto indicou que um dos mecanismos envolvidos na fotoestabilização dos filtros BMBM e EHMC é a supressão do estado energético singleto. Os resultados reportados neste estudo indicaram que a adição da rutina em formulações fotoprotetoras representa um caminho simples e efetivo para elevar a fotoestabilidade da combinação dos filtros BMBM e EHMC. A adição da rutina em formulações fotoprotetoras representa uma estratégia promissora, pois aliada a ação fotoestabilizadora, verificada nesse estudo, esse flavonoide possui propriedades antioxidante e quelante de metais que podem colaborar para o desenvolvimento de formulações fotoprotetoras de amplo espectro com aumento da segurança e eficácia. / In order to promote broad-spectrum protection, most sunscreens are associated with at least two organic filters (UVA and UVB). The combination of avobenzone (BMBM), UVA filter, and octyl methoxycinnamate (EHMC), UVB filter, is well known and widely used in industrial formulations and pharmaceutical compounding, but shows alteration in spectral absorption after UV radiation exposure. The most commonly used strategy to reduce the instability of the combination is based on the addition of photostabilizer agents. The addition of natural substances in sunscreen formulations has been explored, especially the group of flavonoids such as rutin, which shows positive results regarding photoprotective efficacy. The main objective of this research was to evaluate the potential of rutin as a photostabilizer substance of EHMC and BMBM. Formulations were developed containing the two filters associated or not with rutin, according to factorial design at three levels. The formulations were evaluated for in vitro photoprotective efficacy applied on PMMA plates and analyzed by spectrophotometer with integrating sphere reflectance before and after exposure to UV radiation. Molecular interactions of filters with rutin were evaluated by 1H NMR, DSC, TG and qualitative analysis of the suppression of singlet energy state. The addition of rutin in the formulations containing 5.0 % (w/w) BMBM and 10.0 % (w/w) EHMC promoted an increase in the preservation of in vitro SPF of 53.9% to 65.8 (0.1 % rutin) and 70.8 % (1.0% rutin). The DSC and TG curves of rutin showed changes promoted by the presence of BMBM and EHMC filters, indicating interaction between the flavonoid and filters. After 5760 J cm-2 of UV radiation the value of the trans/cis ratio for the EHMC filter added from the BMBM filter was increased from 5.5 ± 0.1 without addition of rutin, to 12.6 ± 0 4,with the addition of rutin. Qualitative analysis of the suppression of the singlet state indicated that one of the mechanisms involved in the photostabilization BMBM and EHMC filters is suppression of singlet excited state.The results reported in this study indicate that the addition of rutin in sunscreen formulations is a simple and effective way to increase the photostability of the combination of BMBM and EHMC. The addition of rutin in sunscreen formulations represents a promising strategy, for allied with the photostabilization action, observed in this study, this flavonoid has antioxidant and chelating properties of metals that can contribute to the development of broad-spectrum sunscreens formulations with increased safety and efficacy.

Les dilatations des voies urinaires de diagnostic anténatal (DVU) peuvent être transitoires, ou correspondre à une anomalie significative de l'écoulement des urines pouvant entrainer une dégradation de la fonction rénale. L'identification de biomarqueurs urinaires pourrait contribuer à différencier précocement les uropathies des dilatations transitoires. La métabolomique permet l'identification de toutes les molécules de bas poids moléculaire présentes dans un échantillon biologique et la mise en évidence d'une signature métabolique associée à un événement physiopathologique. L'objectif principal de cette thèse est l'identification de marqueurs urinaires pronostiques chez les nouveaux nés présentant une DVU de diagnostic anténatal, par spectroscopie RMN et analyse métabolomique.Soixante-dix nouveau-nés ayant une DVU unilatérale et 90 témoins ont été inclus dans cette étude prospective. Tout d'abord, nous comparons la précision de différentes classifications échographiques pour l'évaluation du risque d'intervention chirurgicale.Ensuite, nous montrons l'absence de différence significative entre les profils métaboliques urinaires des nouveau-nés ayant une DVU et ceux des témoins. Dans une troisième partie, nous démontrons l'influence significative de l'âge, du poids et de la taille sur le profil métabolique urinaire des nouveau-nés. Enfin, nous montrons l'évolution du profil métabolique urinaire avec la croissance chez les nourrissons ayant une DVU.Ce travail permet une meilleure compréhension de la physiopathologie des DVU et de la maturation métabolique des nouveau-nés. Il contribue à identifier des biais potentiels dans les études métaboliques en néonatologie / The prenatal finding of unilateral Urinary Tract Dilatation (UTD) can be transient or represent a significant urinary flow impairment that would lead to progressive deterioration of renal function. Identifying urinary biomarkers could help to differentiate uropathy requiring surgical management from transient dilatation at an early stage.Metabolic phenotyping studies provide untargeted quantification of all detectable low molecular-weight molecules by profiling without any a priori the metabolic signatures of biological samples in connection to physiopathological events.The main objective of this study is to identify diagnosis and prognosis urinary markers for uropathy in newborns with prenatally diagnosed unilateral UTD using 1H-NMR spectroscopy combined with multivariate statistical analyses.A total of 70 newborns with unilateral UTD and 90 controls were included in this prospective study. First, the usefulness of different ultrasound grading systems in predicting the need for surgical intervention is evaluated. Then, we report the absence of significant difference between the urinary metabolic profiles of newborns with UTD and controls. In thethird part, the influence of age, weight and height on the urinary metabolic profiles of healthy newborns is highlighted for the first time, and key-metabolites responsible for this evolution are identified. Finally, we demonstrate the influence of age on the urinary metabolic profiles of children with UTD. This work allows a deeper understanding of the metabolic maturation of healthy newborns. It contributes to identify potential confounding factors for metabolomics investigations in neonatology. It represents a step toward a better comprehension of thephysiopathology of UTD

Com o intuito de promover proteção de amplo espectro, na maioria dos protetores solares estão associados pelo menos dois filtros orgânicos (UVA e UVB). A combinação da avobenzona (BMBM), filtro UVA, e do p--metoxicinamato de octila (EHMC), filtro UVB, é conhecida e muito utilizada em formulações manipulas e industrializadas, porém apresenta alteração na absorção espectral após exposição à radiação UV. A estratégia empregada com maior frequência para reduzir a instabilidade da combinação é baseada na adição de agentes fotoestabilizadores. A adição de substâncias naturais em formulações fotoprotetoras vem sendo explorada, especialmente o grupo dos flavonoides, como a rutina, que apresenta resultados positivos em relação à eficácia fotoprotetora. O objetivo principal desta pesquisa foi avaliar o potencial da rutina como substância fotoestabilizadora dos filtros EHMC e BMBM. Foram desenvolvidas formulações contendo os dois filtros associados ou não com rutina de acordo planejamento fatorial em três níveis. As formulações foram avaliadas quanto a eficácia fotoprotetora in vitro aplicadas em placas de PMMA e analisadas por espectrofotometria de refletância com esfera de integração antes e após a exposição à radiação UV. As interações moleculares dos filtros com a rutina foram avaliadas por 1H RMN, DSC, TG e análise qualitativa da supressão do estado energético singleto. A adição de rutina nas formulações contendo 5,0% (p/p) de BMBM e 10,0% (p/p) de EHMC promoveu elevação na conservação do FPS in vitro de 53,9% para 65,8 (0,1% de rutina) e 70,8% (1,0% de rutina). As curvas DSC e TG da rutina apresentaram alterações promovidas pela presença dos filtros BMBM e EHMC, indicando interação entre o flavonoide e os filtros. Após dose de 5760 J cm-2 de radiação UV o valor da razão trans/cis para o filtro EHMC em solução adicionado do filtro BMBM foi elevado de 5,5±0,1, sem adição de rutina, para 12,6±0,4, com adição da rutina. A análise qualitativa da supressão do estado singleto indicou que um dos mecanismos envolvidos na fotoestabilização dos filtros BMBM e EHMC é a supressão do estado energético singleto. Os resultados reportados neste estudo indicaram que a adição da rutina em formulações fotoprotetoras representa um caminho simples e efetivo para elevar a fotoestabilidade da combinação dos filtros BMBM e EHMC. A adição da rutina em formulações fotoprotetoras representa uma estratégia promissora, pois aliada a ação fotoestabilizadora, verificada nesse estudo, esse flavonoide possui propriedades antioxidante e quelante de metais que podem colaborar para o desenvolvimento de formulações fotoprotetoras de amplo espectro com aumento da segurança e eficácia. / In order to promote broad-spectrum protection, most sunscreens are associated with at least two organic filters (UVA and UVB). The combination of avobenzone (BMBM), UVA filter, and octyl methoxycinnamate (EHMC), UVB filter, is well known and widely used in industrial formulations and pharmaceutical compounding, but shows alteration in spectral absorption after UV radiation exposure. The most commonly used strategy to reduce the instability of the combination is based on the addition of photostabilizer agents. The addition of natural substances in sunscreen formulations has been explored, especially the group of flavonoids such as rutin, which shows positive results regarding photoprotective efficacy. The main objective of this research was to evaluate the potential of rutin as a photostabilizer substance of EHMC and BMBM. Formulations were developed containing the two filters associated or not with rutin, according to factorial design at three levels. The formulations were evaluated for in vitro photoprotective efficacy applied on PMMA plates and analyzed by spectrophotometer with integrating sphere reflectance before and after exposure to UV radiation. Molecular interactions of filters with rutin were evaluated by 1H NMR, DSC, TG and qualitative analysis of the suppression of singlet energy state. The addition of rutin in the formulations containing 5.0 % (w/w) BMBM and 10.0 % (w/w) EHMC promoted an increase in the preservation of in vitro SPF of 53.9% to 65.8 (0.1 % rutin) and 70.8 % (1.0% rutin). The DSC and TG curves of rutin showed changes promoted by the presence of BMBM and EHMC filters, indicating interaction between the flavonoid and filters. After 5760 J cm-2 of UV radiation the value of the trans/cis ratio for the EHMC filter added from the BMBM filter was increased from 5.5 ± 0.1 without addition of rutin, to 12.6 ± 0 4,with the addition of rutin. Qualitative analysis of the suppression of the singlet state indicated that one of the mechanisms involved in the photostabilization BMBM and EHMC filters is suppression of singlet excited state.The results reported in this study indicate that the addition of rutin in sunscreen formulations is a simple and effective way to increase the photostability of the combination of BMBM and EHMC. The addition of rutin in sunscreen formulations represents a promising strategy, for allied with the photostabilization action, observed in this study, this flavonoid has antioxidant and chelating properties of metals that can contribute to the development of broad-spectrum sunscreens formulations with increased safety and efficacy.