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Master's Dissertation
DOI
https://doi.org/10.11606/D.46.2011.tde-18082011-093800
Document
Author
Full name
Andrea Cristina Pio Santos
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2011
Supervisor
Committee
Silva, Denise de Oliveira (President)
Alexiou, Anamaria Dias Pereira
Esposito, Breno Pannia
Title in Portuguese
Preparação e caracterização de materiais híbridos bioinorgânico-orgânicos contendo metalofármacos de cobre-naproxeno e de cobre-sulindaco em acetato de celulose
Keywords in Portuguese
Anti-inflamtórios não-esteróides
Complexos de cobre
Metalofármacos
Sistemas híbridos biocompatíveis
Spray-dryer
Abstract in Portuguese
A bioatividade de complexos metálicos é de grande interesse atual na área de pesquisa de novos medicamentos. Fármacos anti-inflamatórios não-esteróides (FAINEs) são amplamente consumidos para o tratamento de doenças inflamatórias e de dor, mas seu contínuo uso pode ocasionar sérios efeitos colaterais ao trato gastrointestinal (TGI). Metalofármacos alternativos de Cu-FAINEs causam menores danos ao TGI, sem perder a atividade anti-inflamatória. No entanto, alguns destes são pouco solúveis. Adicionalmente, o desenvolvimento de materiais híbridos de FAINEs/polímeros para liberação modificada dos fármacos é interessante do ponto de vista de se aumentar a eficácia terapêutica e minimizar problemas de toxicidade. O objetivo deste trabalho foi investigar metodologia, com emprego de secagem via spray-dryer, para a preparação de materiais híbridos contendo complexos de cobre(II) com os fármacos naproxeno e sulindaco incorporados em acetato de celulose. Dois tipos de materiais híbridos foram obtidos para cada metalofármaco: CuFAINE/AC e CuFAINE/AC/OM, sendo o segundo preparado em presença de óleo mineral (OM). A caracterização destes produtos foi efetuada por análises elementares, espectroscopia vibracional no infravermelho, difratometria de raios X, análise termogravimétrica acoplada a espectrômetro de massas, ressonância paramagnética eletrônica, microscopia eletrônica de varredura e espalhamento de luz dinâmico. Os métodos utilizados levaram à interação dos metalofármacos de CuFAINEs com a matriz polimérica biocompatível de acetato de celulose, gerando materiais híbridos bioinorgânicos-orgânicos. Duas espécies de CuFAINEs: uma dimérica mantendo a estrutura original ([Cu2(FAINE)4(Laxial)2]) e outra monomérica - provavelmente do tipo ([Cu(FAINE)2(Laxial)2]) - foram identificadas nestes materiais. As partículas apresentaram tamanho nanométrico. Os resultados aqui obtidos abrem novas perspectivas para futuros estudos que visem à investigação da viabilidade de usar sistemas como estes para liberação mofidicada dos metalofármacos de CuFAINEs
Title in English
Preparation and characterization of bioinorganic-organic hybrid materials containing copper-naproxen and copper-sulindac metallodrugs into cellulose acetate
Keywords in English
Biocompatible hybrid systems
Copper complexes
Metallodrugs
Non-steroidal anti-inflammatory
Spray-dryer
Abstract in English
The bioactivity of metal complexes has current and high interest in the field of development of new drugs. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely consumed to treat inflammatory diseases and pain. The continuous use of these drugs causes serious side-effects on the gastrointestinal tract (GT). Alternative copper(II)-metallodrugs (CuNSAIDs) show lower GT side-effects without loss of anti-inflammatory activity. However, some of them are poorly water-soluble. In addition, the development of NSAID/biocompatible polymeric hybrid materials for modified-release of pharmaceuticals is of interest to increase therapeutic efficacy and to lower toxicity of drugs. The aim of this work was to investigate a methodology adding the use of spray-drying technique to prepare hybrid materials containing copper(II) complexes with naproxen and sulindac drugs incorporated into cellulose acetate (CA). Two different materials were obtained for each metallodrug: CuNSAID/CA and CuNSAID/CA/MO, being the second one prepared in the presence of mineral oil (MO). The characterization of these products was conducted by elemental analysis, vibrational spectroscopy, powder x-ray diffraction, thermogravimetric analysis coupled to mass spectrometry, electron paramagnetic resonance, scanning electron microscopy and dynamic light scattering. The developed methodologies led to the interaction between the CuNSAIDs and the polymeric matrix generating bioinorganic-organic hybrid materials. Two CuNSAIDs species: a dimeric one that kept the complex original structure [Cu2(FAINE)4(Laxial)2] and a monomeric species, ([Cu(FAINE)2(Laxial)2] were identified in these materials. The particles have shown nanometric size. The obtained results open up new perspectives for future studies with the aim of investigating the availability of using this type of system for modified release of CuNSAIDs metallodrugs.
 
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Publishing Date
2011-08-30
 
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