A multidisciplinary literature survey revealed that copolymeric nanoparticles could be applied in various technologies such as the production of paint, adhesives, packaging material and lately especially drug delivery systems. The specialized application and investigation of copolymers in drug delivery resulted in the synthesis of two series of copolymeric materials, i.e. poly(styrene-co-methyl methacrylate) (P(St-co-MMA)) and poly(styrene-co-ethyl methacrylate) (P(St-co-EMA)) were synthesized via the technique of o/w microemulsion copolymerization. These copolymers have not as yet been utilized to their full potential in the development of new drug delivery systems. However the corresponding hydrophobic homopolymer poly(styrene) (PS) and the hydrophilic homopolymer poly(methyl methacrylate) (PMMA) are known to be biocompatible. Blending of homopolymers could result in novel applications, however is virtually impossible due to their unfavorable mixing entropies. The immiscibility challenge was overcome by the synthesis of copolymers that combined the properties of the immiscible homopolymers. The synthesized particles were analyzed by gel permeation chromatography combined with multi-angle laser light scattering (GPC-MALLS) and attenuated total reflectance Fourier infrared spectroscopy (ATR-FTIR). These characterizations revealed crucial information to better understand the synthesis process and particle properties i.e. molecular weight, nanoparticle size and chemical composition of the materials. Additionally, GPC-MALLS revealed the copolymer chain conformation. These characterizations ultimately guided the selection of appropriate copolymer nanoparticles to develop a controlled-release drug delivery system. The selected copolymers were dissolved in a pharmaceutically acceptable solvent, tetrahydrofuran (THF) together with a drug, rifampin. Solvent casting of this dispersion resulted in the evaporation of the solvent and assembly of numerous microscale copolymer capsules. The rifampin molecules were captured in these microcapsules through a process of phase separation and coacervation. These microcapsules finally sintered to produce a multi-layer film with an unusual honeycomb structure, bridging yet another size scale hierarchy. Characterization of these delivery systems revealed that both series of copolymer materials produced films capable of controlling drug release and that could also potentially prevent biofilm adhesion. / Thesis (Ph.D. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2008.

Submitted by Jean Medeiros (jeanletras@uepb.edu.br) on 2018-05-21T15:38:50Z No. of bitstreams: 1 PDF - Malu Maria Lucas dos Reis.pdf: 17160924 bytes, checksum: 0afe6930cfc0eeac7ba0e0d6a32fa8a1 (MD5) / Approved for entry into archive by Secta BC (secta.csu.bc@uepb.edu.br) on 2018-05-23T16:59:44Z (GMT) No. of bitstreams: 1 PDF - Malu Maria Lucas dos Reis.pdf: 17160924 bytes, checksum: 0afe6930cfc0eeac7ba0e0d6a32fa8a1 (MD5) / Made available in DSpace on 2018-05-23T16:59:44Z (GMT). No. of bitstreams: 1 PDF - Malu Maria Lucas dos Reis.pdf: 17160924 bytes, checksum: 0afe6930cfc0eeac7ba0e0d6a32fa8a1 (MD5) Previous issue date: 2017-02-16 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Infectious diseases are responsible for about 25% deaths worldwide and 45% in underdeveloped countries. Antimicrobials are usually used to fight an established infection, they aim either to eliminate or to impede bacterial growth without causing harm to the patient. Flavone, a molecule derived from flavonoids, has evidence of bactericidal activity, with LogP of 3.37 which indicates high lipophilicity. Therefore, it needs a carrier system with lipophilic characteristics, such as microemulsions (ME) and nanoemulsions (NE) O/A, that are systems indicated to its incorporation and use as a novel drug delivery system (NDDS). The aim of this work was to develop nano/microemulsion systems for the incorporation of flavone, aiming topical application, characterizing them physico-chemically, defining a methodology for drug dosing. For the development of the systems and for the choice of formulations to be studied, the construction of the pseudo-ternary phase diagram was performed, followed by incorporation of the drug (1 mg/mL). From this, the physicochemical characterization of the samples was initiated: macroscopic evaluation, isotropy, pH measurement, refractive index, differential scanning calorimetry (DSC), transmission electron microscopy (MET), Zeta potential, droplet size and polydispersity index. In addition, the validation of an analytical method for flavone assay by UV-VIS spectrophotometer and high-performance liquid chromatography (HPLC) was performed. The NE developed was composed of 10.8% oil phase (isopropyl myristate), 25.87% surfactants (polyethylene glycol (15)-hydroxystearate/sorbitan monooleate 80) and 63.33% water. The ME has 34.5% oil phase, 34.5% surfactants and 31% water. Through isotropy, DSC and MET it was possible to prove that the nanoemulsion is O/A and the ME is a bicontinuous system. The analytical methods were validated, both linear, selective, accurate and robust. The present study was relevant for the area of pharmaceutical technology. We sought to develop novel systems with relevant therapeutic potential, since the proposed systems are unprecedented and the drug has the potential to treat antimicrobial diseases. / As doenças infecto-contagiosas são responsáveis por cerca de 25% das mortes em todo o mundo e 45% nos países subdesenvolvidos. Os antimicrobianos são utilizados para combater uma infecção estabelecida, possuindo a finalidade de eliminar ou impedir o crescimento bacteriano, sem causar danos ao paciente. Os flavonoides surgem como mais uma alternativa no tratamento antibacteriano. A flavona, molécula derivada dos flavonoides, possui indícios de sua atividade bactericida, com LogP de 3,37, que indica alta lipofilia. Logo, necessitamos de um sistema carreador com características lipofílicas, sendo carreadores lipídicos, como as microemulsões (ME) e nanoemulsões (NE) do tipo O/A, sistemas indicados para a sua incorporação e utilização como um novo sistema de liberação de fármacos (NSLF). Os objetivos deste trabalho foram desenvolver sistemas nano/microemulsionados para incorporação da flavona, almejando a aplicação tópica, caracterizá-los físico-quimicamente, definir uma metodologia para doseamento do fármaco. Para o desenvolvimento dos sistemas e escolha das formulações a serem estudadas foi realizada a construção do diagrama de fases pseudo-ternário, seguido de incorporação do fármaco (1 mg/mL). A partir disso, iniciaram-se as devidas caracterizações físico-químicas das amostras: avaliação macroscópica, isotropia, medição do pH, índice de refração, calorimetria exploratória diferencial (DSC), microscopia eletrônica de transmissão (MET), potencial Zeta, tamanho de gotícula e índice de polidispersão, além da validação de método analítico para doseamento de flavona por espectrofotômetro UV-VIS e por cromatrografia líquida de alta eficiência (CLAE). A NE desenvolvida foi constituída de 10,8% de fase oleosa (miristato de isopropila), 25,87% de tensoativos (polietilenoglicol (15)-hidroxiestearato/monooleato de Sorbitan 80) e 63,33% de água. Já a microemulsão, possui 34,5% de fase oleosa, 34,5% de tensoativos e 31% de água. Através da isotropia, DSC e MET foi possível provar que a nanoemulsão é O/A e a microemulsão é bicontínua. Os métodos analíticos foram validados, sendo ambos linear, seletivos, precisos, exatos e robustos. O presente estudo mostrou-se relevante para área de tecnologia farmacêutica. Buscou-se desenvolver sistemas inéditos com potencialidade terapêutica relevante, pois os sistemas propostos são inéditos e o fármaco apresenta potencialidade para tratamento de doenças antimicrobianas.

Orientador: Rosiane Lopes da Cunha / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-25T04:10:36Z (GMT). No. of bitstreams: 1 Santana_RejanedeCastro_D.pdf: 3540578 bytes, checksum: 6ff1903cc61cd3c02a5bc21f49dbd351 (MD5) Previous issue date: 2014 / Resumo: Microemulsões (ME) e cristais líquidos (CL) são sistemas auto-organizáveis com potencial capacidade de solubilização de compostos lipofílicos e hidrofílicos. Microemulsões são formadas por gotas de tamanho reduzido e apresentam aspecto translúcido, enquanto os cristais líquidos apresentam estrutura mais complexa, com fases lamelares, hexagonais ou cúbicas. Entretanto, o estudo de ME e CL compostos por ingredientes biocompatíveis ainda é restrito, assim como a avaliação dos efeitos de cada componente e da temperatura na estrutura e reologia dos sistemas. Desta maneira, o objetivo deste trabalho foi avaliar a estrutura e reologia de ME e CL compostos por água, misturas de surfactantes (Tween 80, Tween 20, Span 80, Span 20 e lecitina), triacilglicerol de cadeia média (TCM) e etanol, em diferentes proporções de TCM:etanol (1:0, 2:1 e 1:2). Diferentes estruturas e comportamentos reológicos foram obtidos dependendo da concentração de água, etanol, tipo de surfactante e temperatura. Inicialmente, o estudo de sistemas contendo somente Tween 80 como surfactante mostrou que o incremento de etanol diminuiu a região de cristal líquido e aumentou a área de microemulsão no diagrama de fases, expandindo a região de micelas reversas para maiores concentrações de água. Além disso, maiores concentrações de etanol produziram sistemas com menor tamanho de partícula (DLS), menor distância (d) entre os planos das estruturas (SAXS) e baixa pseudoplasticidade. Já a avaliação de sistemas contendo inicialmente 70 % (m/m) de Tween 80 como surfactante único e diluídos em água (linha de diluição 7) mostrou que a baixas concentrações de água formaram-se microemulsões A/O com comportamento Newtoniano e tamanho de gota nanométrico. Em concentrações intermediárias de água, cristais líquidos com elevada distância (d) entre os planos das estruturas e de reologia complexa foram produzidos, incluindo fluidos viscoelásticos e com comportamento dependente do tempo de cisalhamento (tixotrópico e anti-tixotrópico). Sistemas com concentração intermediária de água com ausência ou baixa concentração de etanol apresentaram temperatura de transição próximo a 50 °C. Estruturas cúbicas e hexagonais com comportamento do tipo gel foram produzidas a 25 °C, enquanto sistemas desordenados com menor distância (d) entre os planos da estrutura e comportamento do tipo solução diluída foram observados a altas temperaturas. Na última etapa, sistemas compostos por diferentes misturas de surfactantes foram avaliados. Estruturas do tipo micelar e hexagonal prevaleceram em sistemas compostos por Tween, enquanto estruturas lamelares foram também observadas em sistemas de Tween/Span e Tween/Lecitina. Estruturas cúbicas foram observadas somente nos sistemas Tween 80/Lecitina. Uma relação entre os parâmetros estruturais, comportamento reológico e propriedades das misturas de surfactantes (parâmetro crítico de empacotamento - P, e balanço hidrofílico-lipofílico - BHL) foi observada. Misturas de surfactantes com menor BHL produziram cristais líquidos pseudoplásticos e viscoelásticos em elevadas concentrações de surfactante. A maior pseudoplasticidade foi associada à estrutura cristalina ordenada susceptível à quebra ou reorientação sob cisalhamento. Além disso, as propriedades das misturas de surfactantes influenciaram no fenômeno de partição do etanol, levando a maiores parâmetros de cela (a) em sistemas de menor BHL. Conhecendo os efeitos da temperatura, composição, concentração e interação entre componentes, as propriedades dos sistemas, como estrutura e reologia, podem ser preditas ou moduladas de acordo com o interesse tecnológico / Abstract: Microemulsions (ME) and liquid-crystals (LC) are self-assembly structures with potential ability to solubilise both lipophilic and hydrophilic components. Microemulsions are translucent systems formed by small swollen micelles, while liquid crystalline phases exhibit a more complex structure, as lamellar, hexagonal and cubic phases. However, the use of biocompatible ingredients in these systems was scarcely explored, as well as the effect of each component and temperature on the system structure and rheology. Thus, the aim of this work was to evaluate the structure and rheology of ME and LC systems formed by water, surfactant mixtures (Tween 80, Tween 20, Span 80, Span 20 and lecithin), medium-chain triacylglicerol (MCT) and ethanol, at different MCT:ethanol ratios (1:0, 2:1 and 1:2). Systems with different structures and rheology were produced according to water and ethanol concentration, surfactant type and temperature. In the first part of this work systems composed by Tween 80 as surfactant showed that the ethanol increment decreased the liquid crystalline area and increased microemulsion area in the pseudo-ternary diagram, expanding micelles production up to higher water content. Moreover, higher ethanol content produced systems with smaller particle size (DLS), smaller correlation distance (d) (SAXS) and lower pseudosplasticity. The evaluation of dilution line 7 of systems with only Tween 80 as surfactant showed that at W/O microemulsions with Newtonian behavior were produced at low water content. At intermediary water contents, liquid crystalline phases with larger correlation distance (d) and complex rheology were produced, including viscoelastic, thixotropic and anti-thixotropic behavior. Systems with intermediary water content and low water content (or absence) of ethanol showed temperature transition around 50 °C. Cubic and hexagonal structures with gel behavior were produced at 25°C, while disordered systems with smaller correlation distance and dilution solution behavior were produced at high temperatures. In the last part of this study, systems composed of different surfactant mixtures were evaluated. Micelle and hexagonal were the main phases observed on systems composed of Tween, while lamellar structures were also observed in Tween/Span and Tween/lecithin systems. Cubic structures were observed only in Tween 80/lecithin systems. A relationship between structural parameters, rheological behavior and surfactant mixture properties (critical packing parameter - CPP, and hydrophilic-lipophilic balance ¿ HLB) was observed. Surfactant mixtures with lower HLB produced pseudoplastic and viscoelastic liquid crystalline phases at high surfactant concentrations. The higher pseudoplasticity was associated with a structure susceptible to reorientation or to the structure broken under shear. In addition, characteristics of surfactant mixture affected the ethanol partition phenomenon, leading to higher lattice parameters (a) in systems with lower HLB. This discussion concerning the effects of temperature, composition, concentration and components interactions could be used to predict and design system properties, as structure and rheology, according to a variety of technological interest / Doutorado / Engenharia de Alimentos / Doutora em Engenharia de Alimentos

A large number of commercial and some novel Brunel synthesised surfactants have been studied with a view to their potential usefulness for enhanced oil recovery (EOR) application. Ethoxylated phenols and their sulphonated derivatives were given especially high priority. The surfactants were well-characterised in order to understand their EOR potential. High pressure liquid chromatography, mass spectrometry, Raman spectrometry, nuclear magnetic resonance spectrometry and other quantitative techniques were used. Aspects of their behaviour (as single components and as blends with co-surfactants and co-solvents) which have been considered in terms of: (i) phase behaviour with brine and hydrocarbons (ii) adsorption onto various oxide surfaces (iii) interfacial properties such as surface tension, wetting, contact angles and viscosity (iv) stability Three different blends using sulphonated surfactants which: (i) produce a microeinulsion which is stable to high salinity brines over a large temperature range (ii) exhibit low adsorption onto reservoir rock (iii) interfacial tension as low as 10-2mNm-1 have been subsequently optimised. Core flooding tests carried out under reservoir conditions produced an additional 20% of the original-oil-in-place.

Background: Metronidazole (MTZ) is an anti-oxidant and anti-inflammatory agent with beneficial therapeutic properties. The hydrophilic nature of the molecule limits its penetration across the skin. Existing commercial formulations have limitations of inadequate drug concentration present at the target site, which requires frequent administration and poor patient compliance. Objective: The aim of the current study was to develop and evaluate water in oil microemulsion of Metronidazole with higher skin retention for the treatment of inflammatory skin disorders. Methods: Pseudo ternary phase diagrams were used in order to select the appropriate ratio of sur-factant and co-surfactant and identify the microemulsion area. The selected formulation consisted of Capmul MCM as oil, Tween 20 and Span 20 as surfactant and co-surfactant, respectively, and water. The formulation was characterized and evaluated for stability, Ex vivo permeation studies and in vivo anti-inflammatory effect (carrageenan induced rat paw edema, air pouch model), anti-p-soriatic activity (mouse-tail test). Results: The particle size analyses revealed the average diameter and polydispersity index of the selected formulation to be 16 nm and 0.373, respectively. The results of ex vivo permeation studies showed statistically higher mean cumulative amount of MTZ retained in rat skin from microemul-sion, i.e., 21.90 ± 1.92 µg/cm2, which was 6.65 times higher as compared to Marketed gel (Metro-gyl gel®) with 3.29 ± 0.11 µg/cm2 (p<0.05). The results of in vivo studies suggested the microemul-sion based formulation of MTZ to be similar in efficacy to Metrogyl gel®. Conclusion: Research suggests the efficacy of the developed MTZ loaded microemulsion in the treatment of chronic skin inflammatory disorders.

No description available.

No description available.

Rare earth oxides with trivalent lattice dopants have been of great interest to researchers in the recent years due to its potential applications in catalysis and high temperature protective coatings. The ability to store oxygen in rare earths is the basis for catalysis because of the ability to change valence states which causes the presence of intrinsic oxygen vacancies in the crystal lattice. Although, several doped-rare earth oxide systems in micron scale have been investigated, the doping effect in cerium oxide nanoparticles with well characterized particle size has not been studied. The doping of ceria at that small size can be very beneficial to further improve its catalytic properties and alter the high temperature phases in alloy systems. Cost effective room temperature chemical methods are used in the current work to synthesize uniformly distributed undoped and doped (dopants: La, Nd, Sm, Gd, Y and Yb) rare earth oxide nanoparticles. In the present study, the variation of the properties in nanocrystalline ceria (NC) synthesized by microemulsion method is studied as a function of dopant size and its concentration. To further understand, the role of dopant (cation) size on the oxygen vacancy concentration, doped nanocrystalline oxide powders were analyzed by Raman Spectroscopy, X-ray Diffraction (XRD) and X-ray Photoelectron Spectroscopy (XPS). XRD studies showed that lattice parameter change in nanocrystalline oxide by doping trivalent rare earth elements is largely depending on size of trivalent ions. It showed that by doping larger cations (Gd3+ and Y3+) compare to Ce3+ causes lattice expansion where as smaller cations (Yb3+) leads to lattice contraction. It also showed that the lattice expansion or contraction is directly proportional to dopant concentration. The results of Raman Spectroscopy showed that the correlation length decreases resulting in increase in oxygen vacancies for larger trivalent dopants (Sm3+, Gd3+ and Y3+). However, the correlation length increases resulting in decrease in oxygen vacancies for smaller trivalent dopants (Yb3+) compare to nanocrystalline ceria. These nanostructured oxides are further applied to develop high temperature oxidation resistance coatings for austenitic steels. The present study investigates the role of oxygen vacancies in the performance of high temperature oxidation resistance as a function of various trivalent dopants and dopant concentration. NC and La3+ doped nanocrystalline ceria (LDN) particles were coated on AISI 304 stainless steels (SS) and exposed to 1243K in dry air for longer duration and subjected to cycling. The results are further compared with that of micro-ceria (MC) coatings. The coated samples showed 90% improvement in oxidation resistance compared to uncoated and MC coated steels as seen from the SEM cross-sectional studies. XRD analysis showed the presence of chromia in both NC and 20 LDN samples which is absent in uncoated steels. From SIMS depth profiles, Fe, Ni depletion zones are observed in presence of LDN coated sample indicating diffusion through the oxide layer. The role of oxygen vacancies in the nanoceria coatings on the early formation of protective chromia layer is discussed and compared to its micron counterpart. This study helps in understanding the role of oxygen vacancies to protect austenitic stainless steel at high temperature and confirms the oxygen inward diffusion rather cation outward diffusion in rare earth oxide coatings. It also gives an idea to identify the type of dopant and its concentration in nanocrystalline cerium oxide which supplies the critical oxygen partial pressure required at high temperature to form primarily impervious chromia layer.

Microemulsions have important applications in various industries, including enhanced oil recovery, reactions, separations, drug delivery, cosmetics and foods. We investigated two different kinds of water-in-oil microemulsion systems, AOT (bis(2-ethylhexyl) sulfosuccinate) microemulsions with various counterions and perfluorocarbon-based microemulsion gels with triblock copolymers. In the AOT systems, we investigated the viscosity and interdroplet interactions in Ca(AOT)2, Mg(AOT)2 and KAOT microemulsions, and compared our results with the commonly-studied NaAOT/water/decane system. We attribute the differences in behavior to different hydration characteristics of the counterions, and we believe that the results are consistent with a previously proposed charge fluctuation model. Perfluorocarbons (PFCs) are of interest in a variety of biomedical applications as oxygen carriers. We have used triblock copolymer Pluronic® F127 to modify the rheology of PFC-based microemulsions, we have been able to form thermoreversible PFOB (perfluorooctyl bromide)-based gels, and have investigated the phase stability, rheology, microstructure, interactions, and gelation mechanism using scattering, rheometry, and microscopy. Finally, we attempted to use these data to understand the relationship between rheology and structure in soft attractive colloids.

Block copolymer (BCP) phase segregation and self-assembly into two or more distinct domains are primarily dictated by two parameters: the block volume fraction, f, and the product of the segment-segment interaction parameter and the length of polymer chain, XN. The volume fraction determines a block copolymer's phase segregated morphology, whereas XN dictates its overall segregation strength, or phase stability. In order to achieve smaller domain sizes, the interaction parameter must be increased to compensate for the decrease in chain length. In the melt, PEO-b-PPO-b-PEO (Pluronic) triblock copolymer surfactants do not phase segregate primarily due to their low molecular weights and insufficient segregation strength, or low XN. Strong hydrogen bonding and selective interactions of PEO chains with homopolymers capable of hydrogen bonding, such as poly(acrylic acid) were shown to increase the effective segregation strength of the blend. Small angle X-ray scattering demonstrated highly ordered sub-10 nm domains resulting from phase segregation of the blends. The strong hydrogen bonding interaction between PEO and H-bonding homopolymers was also utilized to incorporate polyhedral oligomeric silsesquioxanes (POSS) into silicate films. In order to improve the compatibility between hydrophobic POSS with hydrophilic Pluronic copolymers, POSS-decorated acrylate monomer was copolymerized with acrylic acid. This eliminated the macrophase segregation between the BCP templates and POSS molecules. The inclusion of POSS is shown to increase the mechanical performance of the low-k films. A supercritical CO2 synthesis route enables the transport of silica precursors into the polymer blends. An increase of hardness of up to 1.8 GPa at k = 2.4 and 1.2 GPa for k = 2.1 was observed for these mesoporous organosilicate films. Finally, this work has also focused on the formation of ordered domains of the Pluronic surfactants into a ternary solvent system consisting of two liquid solvents and compressed CO2. Compressed CO2 can influence the compatibility of liquid solvents, inducing phase separation or phase mixing. CO2-induced phase separation of acetone and water and phase mixing of tetradecane and methanol were studied for the formation and breaking of nanoscale domains in the presence of Pluronic surfactants. Long-range ordered structures were observed using small angle neutron scattering.