Neste trabalho foram desenvolvidas micropartículas híbridas em pó constituídas de uma matriz biodegradável de quitosana incorporada de partículas de nanogéis biocompatíveis sensíveis à temperatura e/ou ao pH para controlar a liberação de cetoprofeno e aumentar sua solubilidade. Cetoprofeno foi encapsulado em nanopartículas de poli(Nvinilcaprolactama- co-ácido itacônico-co-dimetacrilato de etilenoglicol) (poli(NVCL-co- AI-co-EGDMA)-cetoprofeno), sintetizadas via polimerização por precipitação, as quais foram incorporadas em matriz de quitosana (95% desacetilada e Mv) com os objetivos de melhorar a adesão das micropartículas híbridas no local de liberação e de auxiliar no controle de liberação do fármaco. As micropartículas híbridas de quitosana/poli(NVCL-co-AI-co-EGDMA)-cetoprofeno foram preparadas por interação eletrostática entre os polímeros dispersos em meio aquoso, seguida de secagem por pulverização (spray drying) a fim de melhorar a estabilidadedas micropartículas. Inicialmente foi realizado um estudo sobre a influência das concentrações de monômeros e de iniciador no diâmetro hidrodinâmico (Dh) e na sensibilidade à temperatura e ao pH das partículas de nanogéis. Duas formulações de nanogéis contendo partículas com diferentes valores de Dh (R51 = 185,9 nm e R50 = 120,6 nm) foram utilizadas para a encapsulação de cetoprofeno. As morfologias das partículas de nanogel e das micropartículas híbridas foram avaliadas por microscopias eletrônicas de transmissão e de varredura, respectivamente. Calorimetria diferencial de varredura (DSC), difração de raios X (DRX) e espectroscopia de infravermelho por transformada de Fourier (FTIR) foram utilizadas para analisar as propriedades térmicas, confirmar a encapsulação de cetoprofeno e avaliar qualitativamente a composição dos materiais e interações entre as matrizes poliméricas, respectivamente. Os resultados mostraram que o cetoprofeno foi amorfizado e encapsulado pela matriz de poli(NVCL-co-AI-co-EGDMA), com uma eficiência de encapsulação de 39,6% e 57,8% para as partículas R50 e R51, respectivamente. As matrizes poliméricas de quitosana e de poli(NVCL-co-AI-co-EGDMA) interagiram durante a sua mistura física e durante o processo de secagem, e a cristalinidade da quitosana diminuiu com a incorporação de partículas de nanogel em sua matriz. Os testes de liberação de cetoprofeno in vitro mostraram que as partículas de nanogéis conseguiram controlar a liberação de cetoprofeno e que liberaram 100% do fármaco encapsulado durante 52h de teste, na condição de pH 7,4 e a 37°C. Os testes também evidenciaram que o tamanho das partículas de nanogel foi o parâmetro que mais interferiu na difusão do cetoprofeno pelas partículas, e que a liberação de cetoprofeno foi mais acelerada para as partículas menores (reação R50). Nas mesmas condições de teste, a incorporação das partículas de nanogel na matriz de quitosana causou um retardo na liberação do cetoprofeno, devido à insolubilidade da quitosana no pH 7,4. E os resultados mostraram que para as micropartículas híbridas com maior concentração de partículas de nanogel com relação à massa de quitosana, a liberação de cetoprofeno foi menos acentuada. Isso ocorreu devido ao maior número de interações entre as matrizes poliméricas, o que limitou o contato das partículas de nanogel com o meio de liberação e diminuiu o grau de liberdade de suas cadeias poliméricas. / In this work, powdered hybrid microparticles composed by a chitosan biodegradable matrix embedded with biocompatible and thermo- and pH-responsive particles-based nanogels were developed and used to control the ketoprofen release and to increase its solubility. Ketoprofen was loaded in poly(N-vinylcaprolactam-co-itaconic acid-coethylene glycol dimethacrylate)-based nanogels (poly(NVCL-co-AI-co-EGDMA)- ketoprofen) synthetized by precipitation polymerization, which were embedded in chitosan matrix (95% deacetilation and Mv) aiming to improve the mucoadhesive properties of hybrid microparticles on the targeted tissue and to support in the control of drug release. Hybrid microparticles of chitosan/poly(NVCL-co-AI-co-EGDMA)- ketoprofen were prepared by electrostatic interactions between polymers dispersed in aqueous media and spray-dried in order to improve the microparticles stability. First, it was carried out a study about the influence of monomers and initiator concentrations in the size (hydrodynamic diameter) and thermo- and pH-responsiveness properties of particles-based nanogels. Two formulations of nanogels with different particle sizes (R51 = 185.9 nm e R50 = 120.6 nm) were used to encapsulate ketoprofen. The morphology of particles-based nanogels and hybrid microparticles was studied by transmission and scanning electron microscopies, respectively. Differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) were used to study thermal properties, to confirm encapsulation of ketoprofen and qualitatively evaluate the composition of materials and interactions between polymeric matrices, respectively. The results showed that ketoprofen was converted from the crystalline to the amorphous state and was encapsulated by poly(NVCL-co-AI-co-EGDMA) matrix, with an encapsulation efficiency of 39.6% and 57.8%, for particles R50 and R51, respectively. Polymeric matrices of chitosan and poly(NVCL-co-AI-co-EGDMA) interacted during their mixture and drying process, and chitosan crystallinity decreased as a result of the incorporation of particles-based nanogels in their matrix. In vitro release tests of ketoprofen showed that poly(NVCL-co-AI-co-EGDMA)-based nanogels controlled the delivery of ketoprofen and 100% of ketoprofen-loaded has been released after 52h of the tests, carried out in pH 7.4 at 37°C. These tests also showed that the particles-based nanogels size was the parameter that most interfered in the ketoprofen diffusion by particles and that the ketoprofen release from smaller particles (R50 reaction) was faster. Under the same conditions, the incorporation of poly(NVCL-co-AI-co-EGDMA)-based nanogels in chitosan matrix slowed the ketoprofen release, due to insolubility of chitosan in the media at pH 7.4. The results showed that hybrid microparticles with a higher concentration of particles-based nanogels, with respect to the mass of chitosan, the release of ketoprofen was less pronounced. It was due to the greater number of interactions between the polymer matrices, which limited the contact of particles-based nanogels with the media of release and reduced the degree of freedom of the polymeric chains.

Made available in DSpace on 2015-02-24T17:42:52Z (GMT). No. of bitstreams: 1 ThalesRFP_DISSERT.pdf: 5363462 bytes, checksum: 16f2d3a123870a2d8c63de00ac4bf689 (MD5) Previous issue date: 2014-02-24 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Helicobacter pylori is the main cause of gastritis, gastroduodenal ulcer disease and gastric cancer. The most recommended treatment for eradication of this bacteria often leads to side effects and patient poor compliance, which induce treatment failure. Magnetic drug targeting is a very efficient method that overcomes these drawbacks through association of the drug with a magnetic compound. Such approach may allow such systems to be placed slowed down to a specific target area by an external magnetic field. This work reports a study of the synthesis and characterization of polymeric magnetic particles loaded with the currently used antimicrobial agents for the treatment of Helicobacter pylori infections, aiming the production of magnetic drug delivery system by oral route. Optical microscopy, scanning electron microscopy, transmission electron microscopy, x-ray powder diffraction, nitrogen adsorption/desorption isotherms and vibrating sample magnetometry revealed that the magnetite particles, produced by the co-precipitation method, consisted of a large number of aggregated nanometer-size crystallites (about 6 nm), creating superparamagnetic micrometer with high magnetic susceptibility particles with an average diameter of 6.8 ? 0.2 μm. Also, the polymeric magnetic particles produced by spray drying had a core-shell structure based on magnetite microparticles, amoxicillin and clarithromycin and coated with Eudragit? S100. The system presented an average diameter of 14.2 ? 0.2 μm. The amount of magnetite present in the system may be tailored by suitably controlling the suspension used to feed the spray dryer. In the present work it was 2.9% (w/w). The magnetic system produced may prove to be very promising for eradication of Helicobacter pylori infections / A Helicobacter pylori ? a principal causa de gastrites, ?lceras gastroduodenais e c?ncer g?strico. O esquema terap?utico de primeira escolha para a erradica??o desse pat?geno leva muitas vezes a elevado n?mero de rea??es adversas, baixa ades?o do paciente e consequentemente falha na terap?utica. A vetoriza??o magn?tica ? uma t?cnica bastante difundida na literatura que visa minimizar esses problemas, atrav?s da associa??o de f?rmacos a n?cleos magn?ticos direcionando para o local de a??o por interm?dio de campo magn?tico externo. O presente trabalho relata o estudo da s?ntese e caracteriza??o de part?culas polim?ricas magn?ticas contendo os mais frequentes antimicrobianos (amoxicilina e claritromicina) usados no tratamento de infec??es por Helicobacter pylori, objetivando a produ??o de um sistema para vetoriza??o magn?tica por via oral. Granulometria baseada no di?metro de Feret, microscopia eletr?nica de varredura e transmiss?o, difratometria de raio-x, isotermas de adsor??o/dessor??o de nitrog?nio e magnetometria de amostra vibrante revelaram que as part?culas de magnetita, produzidas pelo m?todo da coprecipita??o, consistem em grande n?mero de agregados de cristalitos de tamanhos nanom?tricos (da ordem de 6 nm) os quais formam part?culas microm?tricas superparamagn?ticas de alta susceptibilidade magn?tica, tendo formato irregular com di?metro m?dio de 6,8 ? 0,2 μm. Os n?cleos magn?ticos foram revestidos por pol?mero (Eudragit? S100) em conjunto com amoxicilina e claritromicina (forma polim?rfica II) sendo obtido micropart?culas n?cleo-camada de formato irregular, pela t?cnica de secagem por aspers?o (spray dryer), com um di?metro m?dio de 14,2 ? 0,2 μm. A quantidade de magnetita presente no sistema pode ser adaptada pelo controle da suspens?o inicial usada na alimenta??o do spray dryer. No presente trabalho o conte?do magn?tico final foi estimado em 2,9 % (p/p). Com base nos resultados obtidos, o sistema magn?tico produzido pode se tornar bastante promissor na erradica??o de infec??es por Helicobacter pylori

Made available in DSpace on 2014-12-17T15:01:44Z (GMT). No. of bitstreams: 1 UlissesCOF.pdf: 4000133 bytes, checksum: 2f1689ba64508ae157f48710d758ba50 (MD5) Previous issue date: 2007-11-01 / This work presents a spray-dryer designed to oxalate-niobate precursors and suitable for the production of Niobium Carbide. The dryer was intended to produce powders of controlled particle size. First, the precursor is dissolved in water to produce a solution of known concentration and then it is atomized on the spray-dryer to produce the powder. This equipment consists of a 304 stainless steel chamber, 0.48 m x 1.9 m (diameter x length), with a conical shape at the lower portion, which is assembled on a vertical platform. The chamber is heated by three 4 kW electrical resistances. In this process, drying air is heated as it flows inside a serpentine surrounding the chamber, in contrary to more traditional processes in which the hot drying air is used to heat the component. The air enters the chamber at the same temperature of the chamber, thus avoiding adherence of particles on the internal surface. The low speed flow is concurrent, directed from the top to the bottom portion of the chamber. Powders are deposited on a 0.4 m diameter tray, which separates the cylindrical portion from the conical portion of the chamber. The humid air is discharged though a plug placed underneath the collecting tray. A factorial experimental planning was prepared to study the influence of five parameters (concentration, input flow, operation temperature, drying air flow and spray air flow) on the characteristics of the powders produced. Particle size distribution and shape were measured by laser granulometry and scanning electronic microscopy. Then, the powders are submitted to reaction in a CH4 / H2 atmosphere to compare the characteristics of spray-dried powders with powders synthetizided by conventional methods / O presente trabalho consiste em projetar e construir um secador spray com a finalidade de secar precursores do tipo oxalato-niobato de am?nia para obten??o de p?s com granulometria controlada e adequados ? produ??o de carbetos de Ni?bio policristalino. Este precursor ? atualmente obtido com granulometria dispersa, e morfologia n?o uniforme. A secagem em spray pode uniformizar as propriedades de materiais que s?o dissolvidos em ?gua, gerando uma solu??o de concentra??o conhecida que ? ent?o, atomizada no secador spray visando ? obten??o do material na forma de p?. O secador ? constitu?do por uma c?mara de secagem em a?o inox 304 medindo 0,48 m de di?metro por 1,90 m de comprimento, montado em uma plataforma vertical e com formato tronco c?nico na sua parte inferior. A c?mara ? aquecida por tr?s cintas de resist?ncias eletricas com pot?ncia total de 4 kW e o ar ? aquecido ao passar por serpentinas constru?das ao redor da c?mara de secagem. O sistema foi projetado de maneira n?o convencional tendo como objetivo principal a produ??o de p?s de precursores com granulometria fina e com uma boa distribui??o do tamanho das part?culas. Foi realizado um planejamento fatorial experimental visando ? an?lise da influ?ncia de cinco par?metros (concentra??o, vaz?o da alimenta??o, temperatura de opera??o, vaz?o do ar de secagem e vaz?o do ar do atomizador) sobre as caracter?sticas dos p?s obtidos usando-se solu??es de bicarbonato de s?dio. As Caracter?sticas f?sicas foram avaliadas a partir de an?lise de ?rea superficial, DRX, tamanho e forma das part?culas, granulometria a laser e microscopia eletr?nica de varredura. Em seguida foi realizada a secagem do precursor e, os p?s obtidos foram submetidos a rea??es com CH4 / H2 com o objetivo de comparar as caracter?sticas dos p?s oriundos do secador spray e aqueles que n?o tiveram esse tratamento. Os resultados mostraram que o equipamento produziu part?culas de bicarbonato de s?dio com di?metros m?dios de 2,4 a 52,4 μm, conforme as temperatura e vaz?es de alimenta??o, e se mostrou capaz de secar precursores do tipo oxalato-niobato de am?nia sem perda de suas caracter?sticas

O presente trabalho teve como objetivo verificar a influência dos parâmetros tecnológicos do processo de secagem por aspersão sobre as características do produto obtido a partir de extrato seco de Maytenus ilicifolia. Para tanto, foi realizado um estudo exploratório, utilizado um desenho experimental fatorial, analisando quatro parâmetros: a concentração de dióxido de silício coloidal (10 e 30 %), o tempo de dispersão em meio líquido das matérias-primas (0,5 e 4 horas), a temperatura de entrada do ar de secagem na torre de aspersão (150 e 180 ºC), e a velocidade de rotação do disco aspersor (9.500 e 11.000 rpm). O teor de umidade residual, a morfologia, a distribuição granulométrica e o fluxo dos pós obtidos, assim como o rendimento do processo e a concentração do marcador catequina foram considerados como respostas ao desenho fatorial. O aumento da temperatura de entrada conduziu a produtos com umidade reduzida e a maior eficiência do processo. A concentração do dióxido de silício coloidal afetou principalmente as propriedades de fluxo e o teor de catequina nos pós produzidos. A maior velocidade de rotação influenciou de modo positivo somente sobre o rendimento do processo. / The present study aimed to evaluate the influence of technological parameters related to the spray drying process over the product obtained from a Maytenus ilicifolia spray dried extract. Therefore, an exploratory study was carried out using an experimental factorial design assessing four parameters: colloidal silicon dioxide concentration (10 – 30 %), dispersion time of the feed material (0.5 – 4 h), air inlet temperature in the spray dryer (150 – 180 ºC), and atomizer speed (9,500 – 11,000 rpm). According to an experimental factorial design four parameters were assessed: colloidal silicon dioxide concentration (10 – 30 %), mixing time (0.5 – 4 h), inlet temperature (150 – 180 ºC), and atomizer speed (9,500 – 11,000 rpm). Moisture content, morphology, particle size, flow, process yield and catechin concentration were considered as responses of the factorial design. Increasing inlet temperature led to dried products with reduced moisture content and higher process yield. Aerosil content mainly affected flow properties and catechin content in the powders. Atomizer speed at high level only enhanced process yield.

Submitted by Gabriela Lopes (gmachadolopesufpel@gmail.com) on 2018-08-13T20:18:31Z No. of bitstreams: 1 tese_Cristina Jansen Alves.pdf: 3092727 bytes, checksum: af2f693596976d2b32a708d78fe4713d (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2018-08-17T12:16:41Z (GMT) No. of bitstreams: 1 tese_Cristina Jansen Alves.pdf: 3092727 bytes, checksum: af2f693596976d2b32a708d78fe4713d (MD5) / Made available in DSpace on 2018-08-17T12:16:41Z (GMT). No. of bitstreams: 1 tese_Cristina Jansen Alves.pdf: 3092727 bytes, checksum: af2f693596976d2b32a708d78fe4713d (MD5) Previous issue date: 2018-03-02 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / A própolis apresenta propriedades benéficas à saúde que são atribuídas a presença de compostos fenólicos, porém, devido ao forte sabor e odor e a baixa solubilidade em água, sua aplicação em alimentos é limitada. A técnica de encapsulação protege os compostos bioativos da degradação, além de tornar possível sua liberação sob condições específicas e aumentar a sua solubilidade. Esta técnica tem sido utilizada para minimizar as características indesejáveis da própolis e facilitar sua aplicação em produtos variados, mantendo sua atividade biológica. Com isto, este estudo teve como objetivo microencapsular extrato de própolis (EP) utilizando como material de parede as proteínas do arroz, da ervilha, da soja e da ovoalbumina, com a técnica de spray drying, para aplicação das micropartículas em alimentos. No capítulo I o EP foi caracterizado quanto aos compostos fenólicos e a capacidade antioxidante. As micropartículas de EP produzidas foram caracterizadas quanto à eficiência, capacidade antioxidante, morfologia, comportamento térmico, grupos funcionais, cristalinidade, rendimento, propriedades físicas, além de ser avaliada a digestão gastrointestinal in vitro após a aplicação das micropartículas em pudim e queijo minas Frescal. O EP apresentou alta concentração de apigenina e luteolina, e as micropartículas apresentaram eficiência de encapsulação superior a 70%. A atividade antioxidante da própolis foi mantida nas micropartículas. As técnicas de DSC, ATR-FTIR e difração de Raios-X confirmaram a encapsulação. As micropartículas variaram em forma, tamanho e características físicas, podendo serem armazenadas em um ambiente de baixa umidade. No queijo a micropartícula de proteína concentrada de ervilha (PCE) demonstrou os melhores resultados na liberação gastrointestinal, uma vez que apresentou maior liberação no intestino, enquanto que as outras micropartículas poderiam ser utilizadas para produção de pudim. No capítulo II foi utilizado como material de parede a PCE, a qual apresentou os melhores resultados no primeiro estudo, e por isso foi utilizada para continuação do trabalho. Micropartículas foram produzidas pelo método de spray drying utilizando diferentes concentrações de EP e de PCE como material de parede. Após, realizou-se a caracterização e a avaliação das atividades antioxidante e antimicrobiana das micropartículas produzidas. A melhor concentração de EP foi de 5% (p/v) e de PCE foi de 2% (p/v), por apresentar a maior eficiência de encapsulação, maior atividade antioxidante e melhor rendimento. O aumento na concentração do EP e da PCE nas micropartículas não influenciou na morfologia das micropartículas, as quais apresentaram superfície arredondada com dobras e concavidades. O ATR-FTIR e a difração de Raios-X confirmaram a encapsulação do EP e demonstraram que a microencapsulação possibilitou uma proteção do EP. O EP apresentou atividade antimicrobiana frente a bactérias Gram-positivas e Gram-negativas, e as micropartículas com 2% de PCE, e com 2,5% e 5% de EP apresentaram efeito bacteriostático e bactericida contra Staphylococcus aureus e Listeria monocytogenes. No capítulo III, o uso de proteína concentrada de ervilha (PCE) em diferentes concentrações para a microencapsulação de EP foi analisado, juntamente com as propriedades físicas, morfológicas e de estabilidade térmica das micropartículas. Além disso, as micropartículas com maior eficiência de encapsulação foram incorporadas em bolo, o qual foi avaliado em diversos parâmetros sensoriais. Das três formulações testadas usando diferentes concentrações de PCE, as micropartículas com PCE 2% apresentaram a maior eficiência de encapsulação e maior estabilidade térmica em relação ao EP puro. Apesar do spray drying ter causado redução no total de compostos fenólicos analisados, a atividade antioxidante das micropartículas não foi afetada. Porém, ocorreu redução no teor de compostos fenólicos e na atividade antioxidante das micropartículas após o forneamento. A formulação PCE 2% foi adicionada na elaboração de bolo, sendo que as características de cor, sabor, odor e textura deste foram semelhantes as do bolo controle. / Propolis has health benefits that are attributed to the presence of phenolic compounds, but due to its strong taste and odor and low solubility in water, its application in food is limited. The encapsulation technique protects the bioactive compounds from degradation, in addition makes possible their release under specific conditions and increase their solubility. This technique was used to minimize the undesirable properties of propolis and its application in varied products, maintaining its biological activities. This study aimed at microencapsulate extract of propolis (PE) using as wall material rice, pea, soybean and egg albumin proteins, with a spray-drying technique, intending apply the microparticles in foods. In Chapter I the EP was characterized for the phenolic compounds and antioxidant capacity. The microparticles of EP produced were characterized in terms of efficiency, antioxidant capacity, morphology, thermal behavior, functional groups, crystal, yield and physical properties, and the gastrointestinal digestion was evaluated in vitro after application of the microparticles in pudding and cheese mines Frescal. The EP presented high concentration of apigenin and luteolin, and the microparticles presented encapsulation efficiency superior to 70%. The antioxidant activity of propolis was maintained in the microparticles. The DSC, ATR-FTIR and X-ray diffraction techniques confirmed the encapsulation. As the microparticles varied in shapes, equipment and physical characteristics, they could be stored in a low-unit environment. The microparticle of concentrated protein of pea (PCE) demonstrated the best results in the gastrointestinal release when it was incorpored in cheese, since they present a greater liberation without intestine, whereas like other microparticles would be for pudding production. In chapter II it was used as wall material PCE, which one presented the best results in the preliminary study (chapter I). Microparticles were produced by the spray-drying method, using different concentrations of EP and PCE as the wall material. Afterwards, it were characterized and evaluated the antioxidant and antimicrobial activities of the microparticles produced. The best EP concentration was 5% (w / v) and PCE was 2% (w / v), due to its higher encapsulation efficiency, higher antioxidant activity and better yield. The increase in the concentration of PE and PCE in the microparticles did not influence the morphology of the microparticles, as they presented a rounded surface with folds and concavities. ATR-FTIR and an X-ray diffraction confirmed encapsulation of PE and demonstrated that a microencapsulation protected the EP. The EP presented antimicrobial activity against Gram-positive and Gram-negative bacteria, and as microparticles with 2% PCE and with 2.5% and 5% of EP presented bacteriostatic and bactericidal effect against Staphylococcus aureus and Listeria monocytogenes. In Chapter III, the use of concentrated pea protein (PCE) at different concentrations for microencapsulation of PE was analyzed, along with the physical, morphological and thermal stability properties of the microparticles. In addition, microparticles with higher encapsulation efficiency were incorporated in cake, which was evaluated in several sensory parameters. Of the three formulations tested using different concentrations of PCE, the microparticles with PCE 2% presented higher encapsulation efficiency and greater thermal stability over pure EP. Despite spray drying caused reduction of phenolic compounds content, the antioxidant activity of the microparticles was not affected. However, there was a reduction in the content of phenolic compounds and in the antioxidant activity of the microparticles after cooking process. A 2% PCE formulation was added in cake making the color, flavor, odor and texture characteristics similar as for control cake.

Le principal objectif de ce travail de thèse était d’étudier l’influence de la fonctionnalisation des protéines par des sucres ou des polyphénols de raisin dans la formulation et le comportement de microsphères de vitamine A. La formulation de différents conjugués issus soit de la réaction de Maillard soit de la complexation des polyphénols sur les protéines a été effectué sur trois matières premières protéiques : les protéines de pois, le caséinate de sodium de lait de vache et la gélatine de type A porcine. Dans une première partie, les caractéristiques et le pouvoir émulsifiant des conjugués ont été étudiés, et ont confirmé le potentiel de stabilisation d’une huile dans le temps. Une seconde partie s’est concentrée sur les observations au microscope électronique à balayage des microsphères et sur une méthodologie d’observation spécifique à ce genre d’échantillon. Une troisième partie a étudié l’influence des fonctionnalisations sur la stabilité de la vitamine A dans le temps, sur sa libération dans des milieux de digestion gastriques et entériques simulés, et sur la libération de géraniol co-encapsulé. La dernière étude a porté sur le potentiel muco-adhésif des microsphères en utilisant une technique d’analyse originale. / The main objective of this thesis was to study the influence of functionalization of proteins by sugars or grape polyphenols in the vitamin A microsphere formulation and behavior. The formulation of different conjugated stemming either from the Maillard reaction or from the complexation of polyphenols on proteins was made on three proteins : pea proteins, sodium caseinate and type A gelatin. In a first part, the characteristics and the emulsifying power of the combined were studied, and confirmed the potential of stabilization of oil in the time. A second part was on the observations with scanning electron microscope of microspheres and on the methodology of specific observation in this kind of sample. The third part studied the influence of functionalization on vitamin A stability in the time, liberation on gastric or enteric digestion media, and liberation of co-encapsulated geraniol. The last study concerned the muco-adhesive potential of microspheres by using an original analysis.

O ovo é consumido in natura ou processado, e usado como matéria-prima em diversos produtos. A pasteurização e a atomização são os principais processamentos aplicados ao ovo. Diferentes condições de processamento, embalagem e estocagem podem afetar a estabilidade oxidativa lipídica e reduzir a proteção antioxidante natural do ovo. O uso de embalagens onde não haja contato do ovo com a luz e oxigênio, estocagem em temperaturas baixas e uso de antioxidantes podem prevenir a oxidação lipídica. Atualmente, os antioxidantes sintéticos são cada vez mais substituídos por antioxidantes naturais ou feita uma associação entre eles. O alecrim (Rosmarinus officinalis L.) e o chá verde (Camelia sinensis L) constam entre os vegetais com grande potencial antioxidante. Com base no exposto, os objetivos do trabalho foram: a) Padronizar o método do fosfomolibdênio para avaliação da capacidade antioxidante total da fração lipídica (CATL) do ovo; b) Investigar o efeito da pasteurização e da atomização do ovo no que se refere à capacidade antioxidante e à estabilidade oxidativa da fração lipídica do ovo; c) Avaliar a estabilidade oxidativa de ácidos graxos e a capacidade antioxidante do ovo integral pasteurizado atomizado, estocado a 5ºC, por 90 dias; d) Verificar por meio de teste de concentração de antioxidantes, a estabilidade oxidativa lipídica do ovo integral pasteurizado atomizado adicionado da mistura de extrato de alecrim, extrato de chá verde e BHA (butilato de hidroxianisol); e) Otimizar a concentração da mistura de extrato de alecrim, extrato de chá verde e BHA a ser adicionada ao ovo líquido integral pasteurizado, posteriormente atomizado, pelo modelo matemático proposto pela metodologia de superfície de resposta; f) Investigar o efeito da mistura otimizada de extrato de alecrim, extrato de chá verde e BHA na estabilidade oxidativa lipídica do ovo integral pasteurizado atomizado, estocado sob as temperaturas de 5°C e 25ºC, por 90 dias. O método do fosfomolidênio para medir a CATL do ovo apresentou adequação analítica, indicada pela equação de regressão (y = 13,705x + 0,0808), coeficiente de determinação (R2 = 0,9931), limite de detecção (0,005mg α-tocoferol/ mL), limite de quantificação (0,017mg α-tocoferol/ mL), coeficiente de correlação (r = 0,9965), sendo que a precisão não indicou dispersão ao redor da média. A CATL diminuiu com o progresso do processamento e o inverso foi observado quanto aos lipídios, 7-CETO (7-cetocolesterol) e TBARS (substâncias reativas ao ácido tiobarbitúrico). O ovo integral pasteurizado atomizado (OIPA) mantido sob condições de estocagem consideradas ideais permaneceu estável em relação à hidratação, a CATL e as TBARS. Pelo teste de concentração de antioxidantes, foram ensaiadas dez misturas (alecrim, chá verde e BHA) no OIPA e refletiu na sua estabilidade oxidativa lipídica, verificada pelas TBARS, CATL, CT-F (capacidade redutora pelo reativo de Folin - Ciocalteau), AGL (ácidos graxos livres) e AS-233 (substâncias absorvidas a 233 nm). Os resultados mostraram que a metodologia de superfície de resposta (RSM) foi adequada para descrever a formação dos AGL e AS-233 no OIPA, podendo serem usadas para fins preditivos. A otimização da mistura de antioxidantes baseou-se no modelo matemático obtido com as AS-233, onde foi proposto como sistema antioxidante 150ppm de BHA, 600ppm de alecrim e 300ppm de chá verde. As condições de estocagem adotadas e a adição dos antioxidantes foram efetivas para manter estável o OIPA, sendo mais efetivo quando estocado a 5°C. Concluíu-se que o método do fosfomolibdênio apresentou adequação analítica. A pasteurização não afetou os parâmetros analisados (lipídios, TBARS, CATL e 7-CETO), mas a atomização provocou diminuição significativa da CATL, e elevação dos lipídios, TBARS e 7-CETO. Foi mantida a hidratação e a estabilidade oxidativa do OIPA estocado por 90 dias a 5°C, indicando que as condições de embalagem e estocagem foram efetivas. Pelo modelo matemático proposto pela RSM foi constatado que apenas os AGL e AS-233 podem ser usados para fins preditivos, optando-se pela otimização da concentração da mistura de antioxidantes, usando apenas o modelo matemático obtido nas AS-233. Com a presença ou não de antioxidantes, o OIPA estocado a 5°C, ao longo dos 90 dias, apresentou-se mais estável quanto à hidratação e à oxidação lipídica. / Egg is consumed in natura or processed and is used as raw material in various food products. The pasteurization and spray-drying processes are the main processing applied to the egg. Different processing conditions, packaging and storage can affect the lipid oxidative stability and may reduce the natural antioxidant protection of this product. The use of packages in which the egg has no contact with light and oxygen, storage at low temperatures, and the use of antioxidants can prevent lipid oxidation. Currently, synthetic antioxidants have been increasingly replaced by natural antioxidants or an association between synthetic and natural antioxidants is adopted by food companies. Rosemary (Rosmarinus officinalis L.) and green tea (Camellia sinensis L) are among the vegetables that present the highest antioxidant potential. Based on the above-mentioned considerations, the objectives of this research were: a) To standardize the method of phosphomolybdenum to evaluate the total antioxidant capacity of lipid fraction (CATL) egg; b)To investigate the effect of pasteurization and spray-drying on the antioxidant capacity and oxidative stability of the lipid fraction of egg; c) To assess the oxidative stability of fatty acids and the antioxidant capacity of whole egg subjected to pasteurization followed by spray-drying, stored at 5ºC for 90 days, d) To evaluate the by testing the concentration of antioxidants, oxidative stability of the lipid fraction of egg subjected to pasteurization and spray drying, added with a mixture of rosemary and green tea extracts and BHA (butylated hydroxyanisole); e) To optimize the concentration of the mixture composed of rosemary and green tea extracts and BHA to be added to pasteurized liquid egg (and further subjected to spray-drying) by using Response Surface Methodology; f) To investigate the effect of the addition of this optimized mixture of antioxidants on of the lipid fraction of spray-dried egg, stored at temperatures of 5 and 25°C for 90 days. The phosphomolybdenum method CATL of egg presented analytical suitability once it presented a high coefficient of determination (R2 = 0,9931), a regression equation expressed as y = 13.705 + 0.0808 x, a limit of detection of 0.005 mg α- tocopherol/mL, a limit of quantitation of 0.017 mg α-tocopherol/mL, a significant and high correlation coefficient (r = 0.9965), and the accuracy did not indicate dispersion around the mean. The CATL decreased with the progress of processing and the reverse was observed for the lipids, 7-CETO (7-ketocholesterol) and TBARS (thiobarbituric acid reactive substances). The pasteurized spray-dried egg (OIPA), which was kept under ideal storage conditions, remained stable in relation to moisture content, CATL and TBARS. In order to test the concentration of antioxidants to be added to OIPA, a total of 10 mixtures (rosemary, green tea and BHA) were assayed. The addition of antioxidants resulted in a higher oxidative stability of the lipid fraction as measured by TBARS, CATL, CT-F (reduction capacity by using the Folin-Ciocalteau reagent), AGL (free fat acids) and AS-233 (substances that absorb at 233 nm). The results showed that the response surface methodology (RSM) was adequate to describe the development of free fat acids and AS-233 in OIPA, and the RSM model proposed for AS-233 can be used for prediction purposes. The optimization of the antioxidant mixture based on the mathematical model proposed for AS-233 indicated that the mixture of 150ppm of BHA, 600ppm of rosemary extract and 300ppm of green tea extract was the best combination of antioxidants. The adopted storage conditions and the addition of antioxidants to OIPA were effective to maintain the response variables stable, and the stability was higher when OIPA was stored at 5°C. It was concluded that the method of phosphomolybdenum suitability presented analytically. The pasteurization did not affect the analyzed parameters (lipids, TBARS, CATL and 7-CETO), but the spray-drying caused a significant decrease CATL, and an increase in lipids, TBARS and 7-CETO. The hydration and the oxidative stability of OIPA remained stable for 90 days at 5°C, indicating that the packaging and storage conditions were effective. The RSM models proposed for free fat acids and AS-233 could be used for predictive purposes; however, the optimization procedure was performed taken into account only the AS-233 model. The OIPA stored at 5°C for 90 days, with or without the addition of the antioxidant mixture, was more stable in relation to hydration and lipid oxidation.

Les nouvelles molécules thérapeutiques présentent la plupart du temps une faible solubilité aqueuse, à l’origine d’une biodisponibilité restreinte lors de leur administration orale. La réduction de taille des cristaux de substance active à l’échelle submicronique (= production de nanocristaux) s’est imposée comme une voie majeure de formulation au cours de ces dernières années.Afin de pallier des problèmes d’instabilité et d’aboutir à des formes solides pratiques d’utilisation pour les patients, une étape de séchage est généralement effectuée après production des nanocristaux en suspension. L’objectif principal de cette étape est de générer un produit présentant à la fois des propriétés facilitant le déroulement d’étapes procédés avales mais aussi et surtout de prévenir l’agrégation des nanocristaux au risque de compromettre leur dissolution après administration.Plusieurs techniques sont aujourd’hui utilisées dans l’industrie pharmaceutique telle que l’enrobage/granulation en lit d’air fluidisé et le spray drying. Parallèlement à l’élaboration d’une « formulation standard » pour ces deux méthodes de référence, deux techniques innovantes de lyophilisation ont été investiguées dans ce travail. La stabilisation de nanocristaux de kétoconazole par cryopelletization et active freeze drying a été démontrée et les paramètres clefs identifiés. Les produits générés par ces deux techniques, respectivement sous forme de pellets ou de poudre fine, ont été comparés à ceux conçus par enrobage en lit d’air fluidisé et spray drying. En conclusion, ces travaux indiquent que la cryopelletization et l’active freeze drying se positionnent comme des procédés d’intérêt de seconde intention, permettant de traiter des cas particuliers (molécules sensibles au stress thermique, à l’humidité et/ou couteuses). / Newly active pharmaceutical ingredients very often suffer from low aqueous solubility, a fact that in many cases can lead to poor oral bioavailability. Nanosizing, referring to drug nanocrystals production by size reduction, has demonstrated over the past few years a great potential to overcome this major issue.Since solid oral dosage forms are generally preferred due to stability reasons and patient convenience, the production of nanocrystals in a liquid medium is usually followed by a drying step. The main objective of this drying step is to generate a product suitable for downstream processing operations while at the same time preventing nanocrystal aggregation which can adversely affect the dissolution performance of the dry product in vivo.Several drying techniques such as spray drying and coating/granulation in fluidized bed have been successfully implemented in the pharmaceutical industry. In this work, two innovative freeze drying techniques were investigated and compared to the two above mentioned reference methods. The suitability of cryopelletization and active freeze drying to stabilize ketoconazole nanocrystals has been demonstrated and the key process parameters identified. The formulations generated by these two innovative techniques in the form of pellets or fine powder particles, respectively, were compared to the previously manufactured by fluidized bed and spray drying. In conclusion, this work presents cryopelletization and active freeze drying as suitable second-line processes with potential to address the drying of formulations containing problematic molecules sensible to thermal stress, moisture and/or presenting high production costs.

La principale difficulté lors de l'administration orale d'un ingrédient pharmaceutique actif (API) est de garantir que la dose clinique de l’API sera dissoute dans le volume disponible de liquides gastro-intestinaux. Toutefois, environ 40% des API sur le marché et près de 90% des molécules en cours de développement sont peu solubles dans l’eau et présentent une faible absorption par voie orale, ce qui entraîne une faible biodisponibilité. Les dispersions solides amorphes (ASD) sont considérées comme l’une des stratégies plus efficaces pour résoudre des problèmes de solubilité des principes actifs peu solubles dans l’eau et, ainsi, améliorer leur biodisponibilité orale. En dépit de leur introduction il y a plus de 50 ans comme stratégie pour améliorer l’administration orale des API, la formation et la stabilité physique des ASD font toujours l'objet de recherches approfondies. En effet, plusieurs facteurs peuvent influer sur la stabilité physique des ASD pendant le stockage, parmi lesquels la température de transition vitreuse du mélange binaire API-polymère, la solubilité apparente de l'API dans le polymère, les interactions entre l'API et le polymère et le procédé de fabrication. Cette thèse consistait en deux parties qui avaient pour objectif le développement de nouvelles formulations sous forme d’ASD d'un antirétroviral, l'Efavirenz (EFV), dispersé dans un polymère amphiphile, le Soluplus, en utilisant deux procédés différents, le séchage par atomisation (SD) et l'extrusion à chaud (HME). EFV est l’API BCS de classe II de notre choix car c’est un API qui représente un défi pour les nouvelles formulations. En effet, il a besoin d’ASD plus fortement concentrées, pour lesquelles la stabilité chimique et physique pendant le stockage et la dissolution seront essentielles. Dans le but de développer de manière rationnelle les ASDs EFV- Soluplus à forte concentration, la première partie s'est concentrée sur la construction d'un diagramme de phases EFV-Soluplus en fonction de la composition et de la température. Le diagramme de phases a été construit à partir d'une étude thermique de recristallisation d'un ASD sursaturé (85 %m EFV), générée par séchage par atomisation. À notre connaissance, il s'agit de la première étude à présenter un diagramme de phase pour ce système binaire. Ce diagramme de phases est très utile et démontre que la solubilité de l'EFV dans les solutions varie de 20 %m (25 °C) à 30 %m (40 °C). Les ASD de EFV dans le Soluplus contenant plus de 30 %m d'EFV doivent être surveillées pendant le stockage dans des conditions typiques de température. Ce diagramme de phases peut être considéré comme un outil de pré-formulation pour les chercheurs qui étudient de nouvelles ASD d'EFV dans le Soluplus afin de prédire la stabilité (thermodynamique et cinétique). Les ASD préparées par différentes techniques peuvent afficher des différences dans leurs propriétés physicochimiques. La deuxième partie de cette thèse portait sur la fabrication d’ASD par des procédés HME et SD. Cette étude montre clairement que la formation d’ASD est une stratégie de formulation utile pour améliorer la solubilité dans l'eau et la vitesse de dissolution de l'EFV à partir de mélanges binaires EFV-Soluplus. Les procédés de fabrication (HME et SD) se sont révélés efficaces pour générer des ASD dans une large gamme de compositions en EFV. L'optimisation du ratio EFV-Soluplus peut être utilisée pour adapter la libération cinétique des ASD. Le choix d’une charge EFV élevée dépassant la solubilité thermodynamique de l’EFV dans le Soluplus est possible, mais il convient de prendre en compte sa stabilité cinétique dans le temps. / The main difficulty when an Active Pharmaceutical Ingredient (API) is orally administered is to guarantee that the clinical dose of the API will be dissolved in the available volume of gastrointestinal fluids. However, about 40% of APIs with market approval and nearly 90% of molecules in the discovery pipeline are poorly water-soluble and exhibits a poor oral absorption, which leads to a weak bioavailability. Amorphous solid dispersions (ASD) are considered as one of the most effective strategies to solve solubility limitations of poorly-water soluble compounds and hence, enhance their oral bioavailability. Despite their introduction as technical strategy to enhance oral APIs bioavailability more than 50 years ago, ASD formation and physical stability remains a subject of intense research. Indeed, several factors can influence the physical storage stability of ASD, among them, the glass transition temperature of the API-carrier binary mixture, the apparent solubility of the API in the carrier, interactions between API and carrier, and the manufacturing process. This thesis consisted of two parts that aim on developing new formulations of ASD of an antiretroviral API, Efavirenz (EFV), dispersed in an amphiphilic polymer, Soluplus, by using two different processes, Spray-drying (SD) and Hot-melt extrusion (HME). EFV is the class II BCS API of our choice because it is a challenging API for new formulations. It needs higher-dosed ASDs, for which chemical and physical stability during storage and dissolution will be critical. Aiming a rational development of high-loaded EFV-Soluplus ASDs, the first part focused on the construction of a temperature- composition EFV-Soluplus phase diagram. The phase-diagram was constructed from a thermal study of recrystallization of a supersaturated ASD (85 wt% in EFV), generated by spray drying. To our knowledge, this is the first study reporting a phase-diagram for this binary system. This phase-diagram is very useful and demonstrated that the EFV solubility in Soluplus ranges from 20 wt% (25 °C) to 30 wt% (40 °C). ASD of EFV in Soluplus containing more than 30 wt% of EFV should be monitored over storage under typical temperature conditions. This phase-diagram might be considered as a preformulation tool for researchers studying novel ASD of EFV in Soluplus, to predict (thermodynamic and kinetic) stability. ASD prepared by different techniques can display differences in their physicochemical properties. The second part of this thesis focused on the manufacturing of ASD by HME or SD processes. This study clearly shows that ASD is a useful formulation strategy to improve the aqueous solubility and the dissolution rate of EFV from EFV-Soluplus binary mixtures. HME and SD manufacturing processes demonstrated to be efficient to generate ASDs in a large range of compositions and loads of EFV. The optimization of EFV to Soluplus ratio can be used to tailor the release kinetics from ASD. The choice of a high EFV load exceeding the thermodynamic solid solubility in Soluplus is possible but it needs the consideration of its kinetic stability over time.

Tesis por compendio / [ES] El proceso de emulsificación de aceites ricos en compuestos bioactivos permite su mejor aplicación y conservación durante el tiempo de almacenamiento. Entre los diversos mecanismos de emulsificación, se destaca el método de Pickering ya que utiliza nanopartículas sólidas naturales en sustitución de los tensioactivos artificiales. Debido a sus propiedades antioxidantes, no toxicidad y disponibilidad, en este trabajo se estudiaron distintas modificaciones del quitosano para su potencial aplicación como partícula de Pickering. Las modificaciones estudiadas fueron la autoagregación, también denominada desprotonación, y el entrecruzamiento con tripolifosfato de sodio. Se evaluó el comportamiento de estas partículas emulsionando aceite de café tostado, un subproducto de la industria de café con un alto contenido de compuestos bioactivos y compuestos volátiles de interés. Posteriormente, se analizaron las propiedades físico-químicas y la estabilidad de las microcápsulas producidas tras el secado de las emulsiones mediante técnicas de secado por atomización y liofilización. Todas las emulsiones se caracterizaron por tener un comportamiento reológico pseudoplástico, sufriendo desintegración a lo largo del proceso de digestión. Las emulsiones formuladas con nanopartículas de quitosano desprotonadas y menor concentración de aceite mostraron una mejor estabilización y, en consecuencia, una mayor bioaccesibilidad de los compuestos fenólicos totales. Las diferentes nanopartículas de quitosano se caracterizaron estudiando su carga superficial, distribución del tamaño de partícula, microestructura y afinidad agua/aceite. A medida que se aumentó la concentración de estas partículas, se afectó positivamente la viscosidad de las emulsiones debido a la formación de una red tridimensional en la fase continua. Las nanopartículas obtenidas al entrecruzar quitosano con tripolifosfato de sodio fueron más pequeñas, dando como resultado emulsiones con gotas más pequeñas. Las emulsiones de Pickering que contenían un 10% de aceite de café tostado se secaron por atomización y se liofilizaron utilizando las diferentes nanopartículas de quitosano estudiadas y maltodextrina como agentes portadores. Las microcápsulas obtenidas tuvieron la humedad, actividad del agua y solubilidad adecuada para su manipulación y almacenamiento. La presencia de nanopartículas de quitosano permitió una mayor retención de aceite en las microcápsulas y mayor eficiencia de encapsulación. Los compuestos bioactivos y las propiedades antioxidantes se conservaron mejor durante la liofilización. Por otro lado, las microcápsulas obtenidas por atomización presentaron mayor protección de estos compuestos durante la digestión. Las microcápsulas formuladas con nanopartículas desprotonadas fueron sometidas a almacenamiento durante 30 días a 25 ºC. Durante el almacenamiento, se evaluó la protección contra la oxidación de lípidos y la liberación de volátiles. Las isotermas de sorción de agua de estas muestras se determinaron también previamente en las condiciones de almacenamiento. Ambas muestras presentaron isotermas del tipo II, lo que permitió un buen ajuste del modelo de GAB a los datos experimentales. La determinación del índice de peróxido y del contenido de dienos conjugados dio lugar a valores adecuados durante el almacenamiento, aunque las muestras liofilizadas presentaron una ligera tendencia a la oxidación debido a la mayor cantidad de aceite superficial. Aunque hubo ligeras diferencias entre las muestras secas, todas mostraron menos pérdida de aromas totales (~28%) en comparación con el aceite no encapsulado (~51%) al final del almacenamiento. Así, se concluyó que las nanopartículas de quitosano estudiadas fueron eficientes para encapsular el aceite de café tostado y preservar sus características frente a la acción de agentes externos. / [CA] El procés d'emulsificació d'olis rics en compostos bioactius permet la seua millor aplicació i conservació durant el temps d'emmagatzematge. Entre els diversos mecanismes d'emulsificació, destaca el mètode de Pickering, ja que utilitza nanopartícules sòlides naturals en substitució als tensioactius artificials. A causa de la seua propietat antioxidant, de la no toxicitat i de la disponibilitat, aquest treball va buscar analitzar el quitosà i les seues modificacions com potencials partícules de Pickering. Les modificacions estudiades van ser la autoagregació, també anomenada desprotonació, i l'entrecreuament amb tripolifosfat de sodi. Es va avaluar el comportament d'aquestes partícules emulsionant oli de cafè torrat, un subproducte de la indústria del cafè amb un alt contingut de compostos bioactius i volàtils d'interès. Posteriorment, es van analitzar les propietats fisicoquímiques i l'estabilitat de les microcàpsules produïdes després de l'assecat de les emulsions mitjançant tècniques d'assecatge per atomització i liofilització. Totes les emulsions tenien un comportament reològic pseudoplàstic, sofrint desintegració al llarg del procés de digestió. Les emulsions formulades amb nanopartícules de quitosà desprotonades i menor concentració d'oli van mostrar una millor estabilització i, en conseqüència, una major bioaccesibilitat als compostos fenòlics totals. Les diferents nanopartícules de quitosà es van caracteritzar estudiant la seua càrrega superficial, distribució del tamany de partícula, microestructura i afinitat aigua/oli. A mesura que es va augmentar la concentració d'aquestes partícules, es va afectar positivament la viscositat de les emulsions a causa de la formació d'una xarxa tridimensional en la fase contínua. Les nanopartícules obtingudes a l'entrecreuar quitosà amb tripolifosfat de sodi van ser més menudes, donant com a resultat emulsions amb gotes més menudes també. Les emulsions de Pickering que contenien un 10% d'oli de cafè torrat es van assecar per atomització i es liofilitzaren utilitzant les diferents nanopartícules de quitosà estudiades i maltodextrina com a agents portadors. Les microcàpsules obtingudes van obtenir una humitat, activitat de l'aigua i solubilitat adequada per a la seua manipulació i emmagatzematge. La presència de nanopartícules de quitosà va permetre major retenció d'oli en les microcàpsules i major eficiència d'encapsulació. Els compostos bioactius i les propietats antioxidants es van conservar millor durant la liofilització. D'altra banda, les microcàpsules obtingudes per atomització presentaren major protecció d'aquests compostos durant la digestió. Les microcàpsules formulades amb nanopartícules desprotonades també van ser sotmeses a la prova d'emmagatzematge durant 30 dies a 25°C. Durant l'emmagatzematge, es va avaluar la seua protecció contra l'oxidació de lípids i l'alliberament de volàtils. Per això, les isotermes de sorció d'aigua d'aquestes mostres es van determinar prèviament en les condicions d'emmagatzematge. Les dues mostres van presentar isotermes de tipus II, el que va permetre un bon ajust del model de GAB a les dades experimentals. L'índex de peròxids i el contingut de diens conjugats van resultar en valors adequats durant l'emmagatzematge, encara que les mostres liofilitzades van presentar una lleugera tendència a l'oxidació a causa de la major quantitat d'oli superficial. Encara que va haver lleugeres diferències entre les mostres seques, totes van mostrar menys pèrdua d'aromes totals (~28%) en comparació amb l'oli no encapsulat (~51%) a la fi de l'emmagatzematge. Així, es va concloure que les nanopartícules de quitosà estudiades van ser eficients per encapsular l'oli de cafè torrat i preservar les seues característiques enfront de l'acció d'agents externs. / [EN] The emulsification process of bioactive-rich oils makes possible their better application and preservation over the storage time. Among the many emulsification mechanisms, the Pickering method has been highlighted as it uses natural solid nanoparticles in replacement of artificial surfactants. Due to the antioxidant properties, non-toxicity and availability, this work aimed at studying chitosan modifications to produce potential Pickering particles. The studied modifications comprised self-aggregation, also called deprotonation, and crosslinking with sodium tripolyphosphate. The performance of these particles was evaluated in the emulsification of roasted coffee oil, a by-product of the coffee industry with a high content of bioactive and volatile compounds of interest. Subsequently, the physicochemical properties and stability of the microcapsules produced after drying the emulsions using spray-drying and lyophilization techniques were analyzed. All emulsions were characterized as shear-thinning, being them destabilized over the digestion process. Emulsions formulated with deprotonated chitosan nanoparticles and lower oil concentrations showed better stabilization and, consequently, greater bioaccessibility of total phenolic compounds. The different chitosan nanoparticles were characterized regarding surface charge, particle size distribution, microstructure and oil/water affinity. Deprotonated chitosan nanoparticles had a larger particle size, which resulted in emulsions with larger oil droplets. As the concentration of these particles increased, the viscosity of the emulsions was positively affected by the formation of a three-dimensional network in the continuous phase. The nanoparticles obtained by crosslinking with sodium tripolyphosphate were smaller, resulting in emulsions with smaller droplets. The viscosity of these emulsions was lower and little affected by the concentration of particles. Pickering emulsions containing 10% roasted coffee oil were spray-dried and freeze-dried, using the different studied chitosan nanoparticles and maltodextrin as carrier agents. The resulting microcapsules showed adequate moisture content, water activity and solubility for subsequent handling and storage. The presence of chitosan nanoparticles resulted in greater oil retention in the microcapsules and higher encapsulation efficiency. Microcapsules obtained by spray-drying had a more regular spherical shape, while the microparticles obtained by freeze-drying were larger with irregular morphology. Bioactive compounds and antioxidant properties were more preserved during freeze-drying. On the other hand, spray drying allowed greater protection of these compounds during the in vitro digestion. The spray- and freeze-dried microcapsules formulated with deprotonated nanoparticles were subjected to the storage test for 30 days at 25 ºC. During storage, their protection against lipid oxidation and volatile release were evaluated. The water sorption isotherms of these samples were previously determined under the storage conditions. Both samples presented type II isotherms, which resulted in a good fitting accuracy of the GAB model to the experimental data. The peroxide index and the conjugated dienes content resulted in adequate values during storage, although the freeze-dried samples showed a slightly higher tendency to oxidation due to the higher amount of surface oil. Although slight differences were observed between the dried samples, both of them showed less loss of total volatile compounds (~28%) when compared to the non-encapsulated oil (~51%) at the end of storage. Thus, it was concluded that the studied chitosan nanoparticles were efficient to encapsulate roasted coffee oil and to preserve its characteristics against the action of external agents. / The authors would like to thank the project RTI-2018-099738-B-C22 from the ‘Ministerio de Ciencia, Innovación y Universidades’, the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brazil (CAPES) - (Finance Code 001; Grant number 88887.468140/2019-00) and the São Paulo Research Foundation (FAPESP – Grant number 2016/22727-8) for the financial support. / Franco Ribeiro, E. (2021). Microencapsulation of roasted coffee oil from chitosan nanoparticles-stabilized Pickering emulsions [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/163234 / TESIS / Compendio