Ce travail décrit la synthèse et l'étude structurale de 1:1-[alpha/alpha-Nalpha-Bn-hydrazino]mères linéaires et cycliques. Après avoir mis au point une méthode générale de synthèse en solution des alpha-Nalpha-hydrazinoesters diversement substitués sur l'azote alpha, ces derniers ont été engagés dans l'élaboration de 1:1-[alpha/alpha-Nalpha-Bn-hydrazino]mères linéaires et cycliques de taille variable. Des études conformationnelles utilisant la RMN, l'IR et les RX ont permis de montrer que la présence de l'azote supplémentaire dans le squelette permettait l'établissement de liaisons hydrogène intramoléculaires conduisant à la formation d'hydrazinoturn. Ainsi l'alternance d'acides alpha-aminés naturels et d'alpha-hydrazinoacides conduit à une auto-structuration des oligomères linéaires par formation de y-turn et d'hydrazinoturn, identique en série hétéro- comme homochirale. En série cyclique, une analyse par RX a permis de mettre en évidence, à l'état solide, la formation de nanotubes due à l'empilement des cyclotétramères hétérochiraux. Cette conformation existe dans le toluène et le dodécane et conduit à la formation d'un gel. Bien que n'ayant pas de preuves de sa structure à l'état solide, le gel formé par le cyclohexamère hétérochiral dans le cyclohexane nous conforte dans l'idée d'une auto-structuration comparable. Les analyses RMN et IR en variation de concentration et température ont quant à elles mis en évidence la dynamique de formation des nanotubes. L'étude sur le cyclotétramère homochiral a cependant montré qu'il ne formait pas de gel. Le gel étant révélateur d'une auto-structuration, ceci nous conduit à nous interroger sur la versatilité du squelette macrocyclique 1:1-[alpha/alpha-Nalpha-Bn-hydrazino] pour l'établissement de nanotubes / This work describes the synthesis and the structural study of linear and cyclic 1:1-[alpha/alpha-Nalpha-Bn-hydrazino]mers. After having designed a general method to synthesize alpha-Nalpha-hydrazinoesters with various surrogates on the alpha nitrogen in solution, these were used to build linear and cyclic 1:1-[alpha/alpha-Nalpha-Bn-hydrazino]mers of varied length. Conformational studies resorting to NMR, IR and X-ray crystallography have shown that the presence of a supplementary nitrogen within the backbone enables to form intramolecular hydrogen bonds, leading to the formation of hydrazinoturns. Thus, the alternation of natural alpha-aminoacids and alpha-hydrazinoacids leads to the autostructuration of the linear oligomers through the formation of y-turns and hydrazinoturns, both in the hetero and homochiral series. In the cyclic series, an X-ray crystallography analysis revealed the formation of nanotubes in the solid state, through the stacking of heterochiral cyclotetramers. This conformation exists in toluene and dodecane and leads to the formation of a gel. Despite having no proof of its structure in the solid state, the gel formed by the heterochiral cyclohexamer in cyclohexane confirms a comparable auto-structuration. Finally, concentration- and temperature-dependant NMR and IR studies have revealed the dynamics of the formation of nanotubes. The study of the homochiral cyclotetramer has however shown that it was not able to form a gel. As the gel is indicative of an auto-structuration, this has led us to question the versatility of the macrocyclic 1:1-[alpha/alpha-Nalpha-Bn-hydrazino] backbone towards the formation of nanotubes

Em 1978, o trabalho realizado por Stephenson e Zamecnik demonstrou a capacidade de um oligonucleotídeo de impedir a expressão de uma proteína específica. Atualmente, duas tecnologias são mais utilizadas para este propósito: os oligodeoxiribonucleotídeos antisense e o RNA de interferência (siRNA), que se aproveitam da capacidade de anelação entre as fitas complementares. A maior diferença entre as duas técnicas é a maquinaria proteica recrutada, isso é, o complexo RISC atua no funcionamento do siRNA, e a protease RNase H atua na clivagem da fita de RNA quando hibridizada com DNA. Apesar da grande aplicabilidade destas tecnologias, tanto para doenças metabólicas quanto para canceres, o veículo de entrega e proteção dessas sequências é de fundamental importância, visto que a aplicação desses oligonucleotídeos livres está sujeita à rápida degradação e ineficiência. A modificação das bases é uma das estratégias para conferir maior estabilidade às sequências, porém estas tem sido relacionadas a um aumento da toxicidade. Nessa dissertação, a quitosana, um polissacarídeo catiônico é utilizado para síntese de nanopartículas e encapsulamento dos oligodeoxiribonucleotídeos antisense (ASO). Para isso, foram realizadas modificações na quitosana comercial como despolimerização, trimetilação ou conjugação com PEG, seguida da síntese das nanopartículas com a adição de tripolifosfato de sódio (TPP) pelo método de gelatinização ionotrópica. A estabilidade das nanopartículas foi medida em função do tempo, da variação de temperatura e da diferença de pH. Além disso, a toxicidade dessas nanopartículas foi analisada através da viabilidade celular em diferentes linhagens, NB-4, HepaRG, HTC e BHK-570. A expressão da proteína verde fluorescente (GFP) na célula NB-4 foi utilizada para avaliar a entrega do ASO desenhado, sendo sua fluorescência monitorada por microscopia confocal. Os resultados demonstram que as nanopartículas se mantiveram estáveis durante o período de tempo analisado, assim como com a temperatura variando de 22 a 45°C e em pH ácido. Cada linhagem celular respondeu de forma diferente ao tratamento com as nanopartículas sem ASO, sendo a linhagem saudável BHK-570 com a maior resistência. Ademais, todas as células apresentaram viabilidade reduzida quando tratadas com concentrações na ordem de 1011 nanopartículas/mL a base de quitosana trimetilada. A fluorescência das células NB-4 quando tratada com as nanopartículas com ASO diminuiu consideravelmente nas 18 primeiras horas, seguida de um aumento após 42 horas. Dessa forma, pode-se concluir que as nanopartículas de quitosana propostas nessa dissertação apresentaram uma excelente alternativa para a entrega de material genético, principalmente para o trato gastro-intestinal, devido à sua estabilidade em pH ácido. / The property of an oligonucleotide to interfere in the expression of a protein was observed in 1978 by Stephenson and Zamecnik. To perform such interference, there are today, two main techniques being explored: antisense oligodeoxyribonucleotides and interference RNA. In both cases, the particularity of their chemical structure is taken into account as soon as they can bind in a complementary manner to the messenger RNA and inhibit its translation. The great difference between these techniques is related to the proteases involved in the process, while for interference RNA the RISC machinery acts, for antisense oligodeoxyribonucleotides RNase H cleaves the RNA in the duplex DNA-RNA. Although these tools to edit the translation process are relevant to the treatment and even cure of metabolic disorders and cancers, it is still not effective when employed without a coating to protect the sequences before it reaches the destiny in vivo. Efforts have been made in developing modified bases to be more stable, but they show some toxicity. In this dissertation, chitosan, a natural cationic polyssacharide, is used to produce nanoparticles to protect the antisense oligodeoxyribonucleotide (ASO). For this reason, the commercial chitosan was modified, depolymerized, trimetilated or PEGlated and the nanoparticles were synthesized with sodium tripolyphosphate (TPP) by ionotropic gelation method. The stability along time, in different pHs and temperatures was assessed. The toxicity of nanoparticles without ASO was quantified by MTT tests in NB-4, HepaRG, HTC and BHK-570 cell lines. A green fluorescent protein (GFP) expressed by NB-4 cells was the target to evaluate the delivery efficiency of the ASO, and its fluorescence was measured by confocal microscopy. Results showed that nanoparticles were stable over time as well as in temperatures ranging from 22 to 45°C and in acidic pH. Each cell line responded in a different manner to the treatment, with the health cell BHK-570 showing higher resistance. Furthermore, all of them presented lower viability when treated with trimetilated chitosan nanoparticles in the highest concentrations (ca 1011 nanoparticles/mL). NB-4 cells presented a decrease in fluorescence in 18 hours of treatment followed by an increase after 42 hours. We conclude that chitosan nanoparticles are a good alternative to the delivery of genetic material even more in the gastro intestinal tract due to its great stability in acid pH values.

Made available in DSpace on 2014-12-17T15:41:55Z (GMT). No. of bitstreams: 1 WildsonAM_DISSERTPPGQ.pdf: 2126383 bytes, checksum: 6a1a9e8b2c55caac2fbd3fb938bff756 (MD5) Previous issue date: 2011-07-20 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Gels consist of soft materials with vast use in several activities, such as in pharmaceutical industry, food science, and coatings/textile applications. In order to obtain these materials, the process of gelification, that can be physical (based on physical interactions) and/or chemical (based on covalent crosslinking), has to be carried out. In this work we used dynamic light scattering (DLS) and rheometry to monitor the covalent gelification of chitosan solutions by glutaraldehyde. Intensity correlation function (ICF) data was obtained from DLS and the exponential stretched Kohrausch-William-Watts function (KWW) was fitted to them. The parameters of the KWW equation, β, Γ and C were evaluated. These methods were effective in clarifying the process of sol-gel transition, with the emergence of non-ergodicity, and determining the range of gelation observed in about 10-20 minutes. The dependence between apparent viscosity on reaction time was used to support the discussion proposed. / G?is s?o materiais que possuem aplica??es em v?rias ?reas, tais quais, na ind?stria de tintas, alimentos e farmac?utica. Os m?todos empregados para obten??o dos g?is podem ser f?sicos (intera??es f?sicas) e/ou qu?micos (baseado em intera??es covalentes), tal processo, ? denominado gelifica??o. Neste trabalho, o processo de gelifica??o de quitosana/glutaralde?do foi monitorado utilizando reometria e espalhamento da luz (DLS). As fun??es de correla??o de intensidade (ICF) foram obtidas atrav?s de DLS e a equa??o de Kohrausch-William-Watts (KWW) foi ajustada com os dados experimentais. Os par?metros da equa??o KWW, β, Γ e C foram avaliados. Estes m?todos foram eficazes na clarifica??o do processo que compreende a transi??o sol-gel, com o surgimento da n?o-ergodicidade, e na determina??o da faixa de gelifica??o, observada em torno de 10-20 minutos. A depend?ncia da viscosidade aparente em fun??o do tempo foi utilizada para comprovar o tempo de gelifica??o observado no DLS.

Wax anti-settling additives (WASA) are used to mitigate against the problems caused by the settling of n-alkane wax crystals, which crystallise from petroleum diesel. This can result in the blocking of fuel filters and hence vehicle failure. However, the mode of action for such additives is not currently known and two mechanisms have been proposed: they reduce the wax crystal size to such an extent that they settle very slowly; or they induce gelation in the wax suspension. This project aims to elucidate the mechanism of WASA within the diesel system. A room temperature crystallising model diesel (10 wt% n-alkanes in dodecane) has been developed. This model system has given a good response to the additives, with the wax crystals reduced in size, and is hence suitable for mechanistic studies. Differential scanning calorimetry and infra-red spectroscopy both suggest that the WASA is incorporated in or onto the wax crystal. DSC shows that small amounts of WASA suppress the wax crystallisation temperature and change the shape of the heat flow curve. FT-IR shows the WASA amide stretch present within filtered and dried wax crystals. Intriguingly, electrophoresis experiments show that the WASA imparts a positive charge to the wax crystals, suggesting an electrostatic role in the WASA action. Rheological experiments show the presence of a weak gel in the WASA doped model diesel. However, the gel strength is not altered by the presence of an organic salt and thus cannot be purely electrostatic in origin. Small angle neutron scattering has been conducted to help locate the WASA in the system. It has shown that in solution WASA shows a collapsed polymer coil structure with a single molecule occupying a 28 Å diameter sphere and multiple WASA molecules forming a 2400 Å diameter sphere. In the presence of the wax the WASA scatter does not significantly change suggesting that the WASA is on the surface of the wax crystal. By combining these results, a mechanism of WASA action is proposed as WASA cations interactions bridging between the wax crystals causing a weak bridging flocculation gel with electrostatic and steric effects contributing to stabilisation. The WASA charges are partially dissociated thus giving the electrophoretic effect and the long chains on the cations can contribute to stability via steric stabilisation.

La viscosité est une propriété fondamentale des fluides complexes et qui reste encore difficile à prédire quantitativement. Cette propriété macroscopique provient de propriétés moléculaires et mésoscopiques. La compréhension et l’estimation de l'évolution de la viscosité avec des paramètres variables est important pour plusieurs applications, entre autres pour l’extraction liquide-liquide et pour la formulation de systèmes tensioactifs aqueux.Dans ce travail, un modèle "minimal" prenant en compte les énergies libres mises en jeu a été développé pour aider à comprendre, contrôler et prédire l'évolution de la viscosité des microémulsions en présence de solutés. Le terme «minimal» signifie dans ce contexte que ce modèle est basé sur un ensemble minimal de paramètres qui sont tous mesurables ou ont une signification physique, ce qui permet d’éviter le recours à des paramètres ajustables. Ce modèle développé dans cette thèse considère les termes chimiques à l'échelle moléculaire, les termes physiques à l'échelle mésoscopique ainsi que les caractéristiques d'écoulement à l'échelle macroscopique a été appliqué sur des microémulsions pauvres en eau utilisé pour l’extraction des métaux ainsi que sur des systèmes tensioactifs anioniques aqueux. / Viscosity is a fundamental property of complex fluids that is still nowadays extremely difficult to predict quantitatively. This macroscopic property originates from molecular and mesoscopic properties. The understanding and prediction of the evolution of the viscosity with changing parameters is crucial for several applications, amongst others for liquid-liquid extraction processes and for formulation of aqueous surfactant systems.In this work, a “minimal” model taking into account the relevant free energies was developed that helps to understand, control and predict the evolution of the viscosity of microemulsions in presence of solutes. The term “minimal” means in that context that this model is based on a minimal set of parameters that are all measurable and have a physical meaning, thus avoiding input of any adjustable parameter. This model that considers the chemical terms at molecular scale, the physical terms at meso-scale as well as the flow characteristics at macroscale was applied on water-poor extracting microemulsions as well as on aqueous anionic surfactant systems.

Ce travail de thèse décrit la formulation d'hydrogels de polygalacturonate (polyGal) réticulés par les cations Fe2+, ainsi que leur caractérisation expérimentale depuis les échelles moléculaires jusqu'aux échelles macroscopiques, en utilisant notamment la spectroscopie d'absorption X (EXAFS), la diffusion de neutrons aux petits angles (DNPA) ainsi que des mesures de rhéologie. Nous avons élaboré un protocole de gélification robuste permettant d'obtenir des gels cylindriques reproductibles qui présentent des gradients de concentrations contrôlés depuis leur partie basale jusqu'à leur partie apicale. Le rapport R = [Fe]/[Gal] a une valeur constante de 0,25 tout au long du gel, ce qui prouve que les cations Fe2+ s'associent avec 4 unités galacturonate. La confrontation des résultats d’EXAFS et de dynamique moléculaire a démontré que ces associations se font via le modèle ''egg-box''. Les mécanismes de réticulation qui contrôlent la structure du réseau formée par les chaînes aux échelles locales sont donc les mêmes dans l'ensemble du gel, ce qui est confirmé par les mesures de DNPA. La formation des gradients de concentration macroscopiques provient des mécanismes de diffusion des cations à travers le gel lors de sa formation. Ces gradients de concentration contrôlent les propriétés mécaniques des gels. En outre, nous avons prouvé que le mode d'association "egg-box" permettait la protection des ions Fe2+ contre l'oxydation, ce qui confère à ces hydrogels un potentiel applicatif pour soigner l'anémie car ils pourraient permettre la vectorisation du fer sous cette forme réduite biodisponible jusqu’à l’intestin.Nous avons étendu notre étude à la formulation d'hydrogels avec d'autres cations (Ca2+ et Zn2+). Ces hydrogels présentent des propriétés macroscopiques proches de celles des hydrogels Fe2+-polyGal car les mécanismes de diffusion des cations régissant la formation des gradients macroscopiques lors de la formation des gels sont similaires. Les hydrogels présentent cependant des structures locales différentes car les modes d'associations locaux varient d"un cation à l’autre. L’ensemble de ces résultats nous a permis de proposer un mécanisme généralisé permettant de décrire les mécanismes de formation d"hydrogels de polygalacturonate pour les cations divalents, et ainsi de moduler finement leur structure sur plusieurs échelles. Ces hydrogels pourraient donc être des outils de choix pour la vectorisation de molécules actives et le contrôle de leur relargage. / This pHD thesis describes the design of polygalacturonate hydrogels (polyGal) cross-linked by the Fe2+ cations, and their experimental characterization from the molecular scales up to the macroscopic scales, by combining EXAFS spectroscopy, Small Angle Neutron Scattering (SANS) and rheological measurements. We designed a robust gelling protocol that allowed to obtain reproducible cylindrical gels with controlled concentration gradients from the lower side to the upper side of the gel. The ratio [Fe]/[Gal] has a constant value all along the gel, which demonstrate that the Fe2+ cations are associated with 4 galacturonate units. The comparison of EXAFS measurements and molecular dynamics simulation has shown that these associations followed the "egg-box" model. The crosslinking mechanisms that control the structure of the network made by the chains at local scale is therefore the same throughout the whole gel, which is confirmed by SANS measurements. The formation of the macroscopic concentration gradients comes from the mechanisms that drive the cations diffusion through the gel during the gelation process. These gradients control the gels mechanical properties. Besides, we proved that the “egg-box" association enables to protect Fe2+ against oxidation, which gives to these hydrogels an applicative potential to cure anemia as they could allow to target iron under its bioavailable form up to the gut.We have extended the study to the design of hydrogels with other cations (Ca2+ et Zn2+). The macroscopic properties of these hydrogels are very close to that of the Fe2+-polyGal hydrogels because the cation diffusion that govern the formation of macroscopic gradients during the gelationg process are similar. The hydrogels have however different local structures because the cation- polyGal local association varies from one cation to another. All these results allowed us to propose a generalized mechanism that describes the polygalacturonate hydrogels formation for divalent cations, and thus to tune their structure over several scales. These hydrogels could therefore be some promising tools for the vectorization of active molecules and the control of their release.

Simple gel formulations may be applied to enhance the systemic and local exposure of potential compounds. The aim of this thesis is the development and characterization of controlled release formulations based on thermo-reversible poloxamer gels, which are suitable for novel drug delivery applications.  In particular co-solvents (DMSO, ethanol), mucoadhesive polymers (chitosan, alginate) and salts (sodium tripolyphosphate, CaCl2) have been used to enhance the applications of poloxamer 407 (P407) formulations in preclinical animal studies. The impact of these additives on the micellization and gelation properties of P407 aqueous solutions was studied by calorimetric methods, nuclear magnetic resonance spectroscopy (NMR) and “tube inversion” experiments. The drug release behavior of hydrophobic and hydrophilic drugs was characterized by using a membrane/membrane-free experimental setup. Finally, preliminary pharmacokinetic studies using a mouse model were conducted for screening of selected inhibitors of bacterial type III secretion and for evaluation of different formulations including P407 gel. All additives, used here, reduced the CMTs (critical micelle temperature) of dilute P407 solutions, with the exception of ethanol. The gelation temperature of concentrated P407 solutions was lowered in the presence of CaCl2, DMSO, TPP and alginate. 1H MAS (Magic Angle Spinning) NMR studies revealed that DMSO influences the hydrophobicity of the PPO segment of P407 polymers. Low concentrations of DMSO did not show any major effect on the drug release from P407 gels and may be used to improve the exposure of lead compounds in poloxamer gels. A newly developed in situ ionotropic gelation of chitosan in combination with TPP in P407 gels showed an enhanced resistance to water and reduced the release rates of model drugs. From preliminary pharmacokinetic studies in mice it was revealed that poloxamer formulations resulted in an increased plasma half-life of the lead compound.

Binding of volatile flavour compounds to plant proteins is known to be an issue, particularly for developers of flavoured gluten-free snacks made with pea protein. This project used a model system to describe the effects of extraction and heat on the binding of hexanal (Hex), hexyl acetate (HxAc) and 2-octanone (2-Oct) to pea protein isolate and to evaluate any resulting change in protein functionality.

Content removed from thesis due to copyright restrictions: Winger, R.J. and L. Ren (2009). "Solubility of sodium and potassium iodates in saturated salt solutions." Food Chemistry 113: 600-601. / This paper was to improve the production of calcium-induced alginate gels manufactured by a company in Auckland. Problems encountered included yield and syneresis of the beads post-gelation. Essentially the alginate, sugars and other ingredients were dissolved in water at 80ºC. The pH of the solution was adjusted and the alginate beads were extruded into a 5% CaCl2 bath before being drained and dried. The chemical reaction between sodium alginate and calcium ions is dependent upon the solubility and availability of calcium ions. Some calcium salts (e.g., CaCl2, calcium lactate) were readily soluble and fully dissociated in water and resulted in an immediate gelation of the alginate. Dicalcium phosphate (DCP) was sparingly soluble at pH 7 and calcium ions were not released significantly until the pH reached about pH 4.2. Sodium hexametaphosphate (SHMP) is a chelating agent and this was used to soak up small quantities of Ca+2 to ensure no gelation occured while the alginate was being mixed. The optimum quantities of alginate, DCP and SHMP were defined in the laboratory trials. The use of SHMP, maltodextrin, and gums significantly affected the hardness and stickiness of gel beads. It was found that the combination of xanthan and alginate Protanal LF 120 gave the best results in terms of minimal stickiness and maximum yield after drying. Key words: alginate gel beads, syneresis, formula, pH, citric acid, gelation time, SHMP, setting time, yield rate, drying, hardness, stickiness, maltodextrin, xanthan gum, guar gum, stickiness by touching, leakage, apparent viscosity.

L'enrichissement d'aliments courants avec des composés bioactifs aide à promouvoir la santé et réduire le risque de maladies. Cependant, la plupart des bioactifs à propriétés biologiques intéressantes sont de nature hydrophobe et donc présentent des limites d’incorporation dans les aliments dues à leur faible solubilité dans les matrices aqueuses. De plus, leurs activités biologiques se heurtent à des facteurs extrêmes lors des procédés de formulation et de fabrication du produit telle que les fluctuations de pH, de température et de pression. Pour ce, l’encapsulation des bioactifs dans des matrices « biosourcée » s’avèrent être une solution pour améliorer leur biodisponibilité et préserver leurs propriétés fonctionnelles. Dans cette étude, nous avons choisi de traiter le cas de la curcumine, composé phénolique hydrophobe présentant diverses activités biologiques intéressantes telles que notamment une activité antioxydante importante, mais dont l'action est limitée de par sa faible biodisponibilité. Le choix de la matrice d’encapsulation s’est porté sur la micelle de caséine, véritable matrice naturelle et efficace aux propriétés technofonctionnelles variées. Cette thèse a permis de démontrer l’interaction hydrophobe entre la micelle de caséine et la curcumine via les résidus tryptophane. L'incorporation de la curcumine au sein de la micelle de caséine n’influence ni les propriétés structurales (taille, charge de surface et structure interne) ni les propriétés fonctionnelles (gélification) de la micelle. Sachant qu'un des objectifs d'application pourrait être la production d’un yaourt enrichi en curcumine, l’étude de l’interaction entre la curcumine et les bactéries lactiques du yaourt est nécessaire. Il a ainsi été démontré que la curcumine s’adsorbe sur les enveloppes bactériennes de Lactobacillus bulgaricus et préférentiellement sur Streptococcus thermophilus sans inhiber leur croissance et leur pouvoir acidifiant. Une fois en contact avec les micelles de caséines et les LAB, la curcumine se partage entre la micelle et les enveloppes bactériennes pour établir un équilibre. Sachant que la plupart des industries agroalimentaires utilisent dans les étapes de formulation des ingrédients sous forme de poudres plutôt que sous forme liquide, la production d’une poudre de micelle de caséine dopée en curcumine préservant l’activité antioxydante du bioactif tout en conservant les propriétés technofonctionnelles de la micelle de caséine a été réalisée par séchage par atomisation / Enriching common foods with bioactive compounds could help promote health and reduce the risk of diseases. However, most bioactives with interesting biological properties are hydrophobic and therefore have incorporation limits in foods due to their low solubility in aqueous matrices. In addition, their biological activities encounter extreme factors in the formulation and manufacturing processes of the product such as pH, temperature and pressure fluctuations. To this end, the encapsulation of the bioactive elements in "bio" matrices is a solution for improving their bioavailability and preserving their functional properties. In our study, we chose to treat curcumin, a hydrophobic phenolic compound, with various interesting biological activities such as its important antioxidant activity. The choice of the encapsulation matrix was turned to the casein micelle, an effective encapsulation matrix with desired technofunctional properties. This thesis has demonstrated the hydrophobic interaction between the casein micelle and curcumin via tryptophan residues. The addition of curcumin in solution to the casein micelle did not influence the structural properties (size, ζ-potential and internal structure) nor the functional properties (gelling) of the micelle. Knowing that the ultimate goal is the production of yogurt enriched with curcumin, the study of the interaction between curcumin and lactic bacteria of yoghurt is necessary. Indeed, curcumin adsorbs on the bacterial envelopes of Lactobacillus bulgaricus and preferentially on Streptococcus thermophilus without inhibiting their growth and their acidifying power. Once in contact with casein micelles and LABs, curcumin is partitioned between the micelle and the bacterial envelopes to establish a balance. Given that most agro-food industries use more powder rather than aqueous solutions in formulation stages, the production of curcumin-doped casein micelle powder protecting the antioxidant activity of the bioactive while preserving the technofunctional properties of the casein micelle was carried out by spray-drying