Obtenção e caracterização de micropartículas de PHB/Qt/Cetoprofeno

TCC (graduação) - Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas, Curso de Química.O objetivo do presente trabalho foi obter micropartículas compostas com um fármaco e controlar liberação do mesmo, otimizando a velocidade de liberação para as aplicações desejadas, diminuindo o efeito burst realease. O fármaco modelo encapsulado foi o cetoprofeno formando micropartículas com o polímero PHB através da técnica emulsão evaporação do solvente O/A.Para a formação de micropartículas compostas de PHB revestidas ou inseridas na matriz de quitosana, utilizou-se a técnica de spray drying. As propriedades morfológicas das micropartículas foram avaliadas, bem como sua eficiência de encapsulação. A eficiência de encapsulação foi da ordem de 36%. Micrografias de microscopia eletrônica de varredura permitiram avaliar o recobrimento do filme de quitosana.O perfil de liberação do fármaco das micropartículas de PHB e PHB/Qt foi obtido em condições tamponadas de uma solução de fosfato pH 7,4 utilizando espectrometria UV-Vis, sendo observado uma redução de liberação de fármaco das micropartículas PHB/Qt, após a reticulação do filme de quitosana. Estes resultados indicam a viabilidade de aplicação no método para encapsulamento de fármacos, sendo necessários estudos posteriores para adequação de parâmetros de preparação da micropartículas

Micropartículas compostas de PHB/cetoprofeno recobertas com quitosana reticulada: obtenção e estudo da liberação controlada do fármaco

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós-Graduação em Ciência e Engenharia de MateriaisMicropartículas de poli(3-hidroxibutirato) (PHB) contendo cetoprofeno (CET) como fármaco modelo foram preparadas através da técnica de emulsão-evaporação do solvente O/A. Com o intuito de atribuir uma barreira adicional à liberação do cetoprofeno, micropartículas de CET/PHB foram revestidas por um filme de quitosana através da técnica spray drying. A quitosana é um dos biopolímeros mais utilizados para aplicações farmacêuticas e biomedicinais, porém, como é um polímero hidrofílico, há necessidade de uma reticulação visando modificar determinadas propriedades do biopolímero, tais como, estabilidade química e térmica, rigidez estrutural, permeabilidade e capacidade de modular a liberação de agentes ativos. O filme de quitosana foi reticulado com glutaraldeído ou genipin. A morfologia das micropartículas foi avaliada, bem como sua eficiência de encapsulação. As micrografias de MEV mostraram partículas esféricas com tamanhos entre 10 a 20 µm. A eficiência de encapsulação foi da mesma ordem de grandeza para todas as formulações de micropartículas estudadas. O perfil de liberação do fármaco foi obtido em condições tamponadas de uma solução de fosfato pH 7,4 utilizando espectrometria UV-Vis. A influência das concentrações de quitosana e do agente reticulante (glutaraldeído e genipin) na quantidade de cetoprofeno liberado após 1 h e sobre o prolongamento de liberação em 72 h, foi avaliada através de análises estatísticas, indicando que ambas as variáveis influenciaram as respostas. A liberação do cetoprofeno a partir de micropartículas compostas recobertas com quitosana reticulada foi lenta e sustentável, sendo um transportador polimérico muito promissor para a libertação de fármacos. Para elucidar o mecanismo de liberação, os sistemas foram tratados com base no modelo de Higuchi e na Lei das Potências, sendo os perfis descritos por uma equação biexponencial. A partir do ajuste dos dados de liberação à equação de Baker-Lonsdale, determinou-se que o mecanismo de liberação é controlado, sobretudo por difusão pelas matrizes poliméricas.Microparticles of poly(3-hydroxybutyrate) (PHB) containing ketoprofen (KET) as a model drug were prepared using the technique of emulsion-evaporation solvent (O/W). In order to assign an additional barrier to the release of the ketoprofen and decrease the burst effect, microparticles of KET/PHB were coated with a film of chitosan by spray drying technique. Chitosan is one of the most biopolymers commonly used for pharmaceutical and biomedical applications, however, as it is a hydrophilic polymer, there is a need for crosslinking in order to modify certain properties of the biopolymer, such as chemical and thermal stability, structural strength, permeability and the ability to modulate the release of active agents. The film surface was modified by two chitosan crosslinking agents, glutaraldehyde and genipin. The morphology of the microparticles was evaluated as well as their encapsulation efficiency. The SEM micrographs showed spherical particles with sizes between 10 and 20 ìm. The encapsulation efficiency was, approximately, the same order for all microparticles with different formulations of chitosan. The profile release of the drug was obtained at a buffered phosphate solution pH 7.4 using UV-Vis spectrometry. The influence of chitosan concentration and and crosslinker agents (glutaraldehyde or genipin) on the amount of ketoprofen released after 1 h and on the extended-release after 72 h was evaluated by statistical analyzes, indicating that both variables influenced the responses. The release of ketoprofen from composite microparticles coated with crosslinked chitosan was slow and sustainable, being a polymeric carrier to a very promising drug delivery. To elucidate the mechanism of release, the systems were treated with the model of Higuchi and power law, these profiles were described by biexponential equation. From the adjustment of the data release to the equation of Baker-Lonsdale, we determined that the release mechanism is controlled primarily by diffusion through polymeric matrices

SARS-CoV-2 recombinant proteins stimulate distinct cellular and humoral immune response profiles in samples from COVID-19 convalescent patients

OBJECTIVES: In this preliminary study we investigated cellular and humoral immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in blood samples from 14 recovered coronavirus disease 2019 (COVID-19) patients and compared them to those in samples from 12 uninfected/unvaccinated volunteers. METHODS: Cellular immunity was assessed by intracellular detection of IFN-γ in CD3+ T lymphocytes after stimulation with SARS-CoV-2 spike (S1), nucleocapsid (NC), or receptor-binding domain (RBD) recombinant proteins or overlapping peptide pools covering the sequence of SARS-CoV-2 spike, membrane and nucleocapsid regions. The humoral response was examined by ELISAs and/or chemiluminescence assays for the presence of serum IgG antibodies directed to SARS-CoV-2 proteins. RESULTS: We observed differences between humoral and cellular immune profiles in response to stimulation with the same proteins. Assays of IgG antibodies directed to SARS-CoV-2 NC, RBD and S1/S2 recombinant proteins were able to differentiate convalescent from uninfected/unvaccinated groups. Cellular immune responses to SARS-CoV-2 protein stimuli did not exhibit a specific response, as T cells from both individuals with no history of contact with SARS-CoV-2 and from recovered donors were able to produce IFN-γ. CONCLUSIONS: Determination of the cellular immune response to stimulation with a pool of SARS-CoV-2 peptides but not with SARS-CoV-2 proteins is able to distinguish convalescent individuals from unexposed individuals. Regarding the humoral immune response, the screening for serum IgG antibodies directed to SARS-CoV-2 proteins has been shown to be specific for the response of recovered individuals

Ionic Liquid as Surfactant Agent of Hydrotalcite: Influence on the Final Properties of Polycaprolactone Matrix

This paper reports the surface treatment of layered double hydroxide (LDH) by using ionic liquid (IL) composed of phosphonium cation combined with 2-ethylhexanoate (EHT) counter anion as surfactant agent. Then, different amounts (1, 3, 5 and 7 wt %) of thermally stable organically modified LDH (up to 350 °C) denoted LDH-EHT were incorporated into polycaprolactone (PCL) matrix by mechanical milling. The influence of LDH-EHT loading has been investigated on the physical properties, such as the thermal and barrier properties, as well as the morphologies of the resulting nanocomposites. Thus, intercalated or microcomposite morphologies were obtained depending on the LDH-EHT loading, leading to significant reduction of the diffusion coefficient respect to water vapor. The modulation of barrier properties, using low functionalized filler amount, is a very important aspect for materials in packaging applications

Etude et développement de fibres électrofilées pour des applications en biotechnologie

Actuellement, le procédé d’électrofilage également appelé electrospinning est une des voies les plus prometteuses permettant le design et le développement de nanofibres polymères poreuses. En effet, cette technique est simple d’utilisation, unique, modulable, à faible coût et est déjà couramment utilisée dans le milieu industriel. De part ces avantages, l’electrospinning fait l’objet d’un engouement grandissant de la recherche académique et industrielle dans plusieurs domaines d’applications tels que ceux de la filtration, la cosmétique, du textile, de l’ingénierie tissulaire et du domaine médical, notamment pour le relargage de molécules actives. De plus, cette technique est applicable sur de nombreux polymères synthétiques ou naturels et il est possible de contrôler de nombreux paramètres tels que la porosité, le diamètre des fibres ou encore la surface accessible. Un des premiers objectifs de cette thèse a été de développer des scaffolds pour le domaine de l’ingénierie des tissus neuronaux afin d’imiter les propriétés biologiques, physiques et mécaniques de la matrice extracellulaire native. Dans un premier temps, l’effet de l’alignement des fibres d’une matrice fluorée (PVDF) biocompatible a été étudié sur le comportement de cellules souches neurales de singe, en particulier les morphologies, l’adhésion cellulaire ainsi que leurs différentiations en cellules gliales ou neuronales. Dans un second temps, des scaffolds bioabsorbables composés de PLA et de PEG ont été synthétisés afin d’étudier l’influence de l’équilibre hydrophile-hydrophobe sur la culture de cellules souches neurales. Et dans une dernière partie, une véritable étude exploratoire a été réalisée afin de développer des textiles intelligents à base de PBAT contenant des curli, protéine bien connue pour sa capacité à chélater des métaux.Currently, the electrospinning process is also one of the most promising routes for the design and development of polymer fibers. This technique is easy to use, unique, versatile, and low cost, which can be used to create fibers from a variety of starting materials. The structure, chemical and mechanical stability, functionality, and other properties of the fibers can be modified to match end applications. The first goal of this thesis was to develop scaffolds for the field of neural tissue engineering in order to mimic the biological, physical and mechanical properties of the native extracellular matrix. In the first time, the effect of fiber alignment of a biocompatible and fluorinated matrix denoted polyvinylidene fluoride (PVDF) was studied on the behavior of monkey neural stem cells particularly the morphology, cell adhesion and their differentiation in glial or neuronal cells. Secondly, bioabsorbable scaffolds composed of polylactide (PLA) and polyethylene glycol (PEG) polymers were synthesized to investigate the influence of the hydrophilic-hydrophobic balance on the culture of neural stem cells. Finally, an exploratory work was conducted to develop smart textiles based on poly(butylene adipate-co-terephthalate) (PBAT) containing curli as protein, well-known for its ability to chelate metals

Ionic Liquid as Surfactant Agent of Hydrotalcite: Influence on the Final Properties of Polycaprolactone Matrix

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Ionic Liquid as Surfactant Agent of Hydrotalcite: Influence on the Final Properties of Polycaprolactone Matrix

This paper reports the surface treatment of layered double hydroxide (LDH) by using ionic liquid (IL) composed of phosphonium cation combined with 2-ethylhexanoate (EHT) counter anion as surfactant agent. Then, different amounts (1, 3, 5 and 7 wt %) of thermally stable organically modified LDH (up to 350 °C) denoted LDH-EHT were incorporated into polycaprolactone (PCL) matrix by mechanical milling. The influence of LDH-EHT loading has been investigated on the physical properties, such as the thermal and barrier properties, as well as the morphologies of the resulting nanocomposites. Thus, intercalated or microcomposite morphologies were obtained depending on the LDH-EHT loading, leading to significant reduction of the diffusion coefficient respect to water vapor. The modulation of barrier properties, using low functionalized filler amount, is a very important aspect for materials in packaging applications

From Ionic Liquid Monomers to Antibacterial Surface Based on New Polymer Networks

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Phosphonium ionic liquid as interfacial agent of layered double hydroxide: Application to a pectin matrix

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Phosphonium ionic liquid as interfacial agent of layered double hydroxide: Application to a pectin matrix

International audienc