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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

SÃntese de Microesferas e NanopartÃculas de Quitosana e Goma do Chichà (Sterculia striata) como Matriz para LiberaÃÃo Controlada de FÃrmaco para Tratamento da MalÃria

Guilherme Augusto Magalhaes Junior 20 April 2012 (has links)
CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior / Este trabalho tem como objetivo a sÃntese e caracterizaÃÃo de nano e micropartÃculas para liberaÃÃo de fÃrmaco para tratamento da malÃria. Microesferas de quitosana de alta massa molar (QTa) e goma do chichà (CH) foram sintetizadas por complexaÃÃo polieletrolÃtica e reticuladas com glutaraldeÃdo. Os diÃmetros das microesferas reticuladas e nÃo-reticuladas foram de 544  3 μm e 558  2 μm, respectivamente. As esferas reticuladas nÃo foram solÃveis em meio Ãcido (pH 1,2). Ensaios de intumescimento mostraram que as microesferas intumesciam mais em pH 1,2 do que em pH 7,4 e que as reticuladas possuÃam menor intumescimento do que as nÃo reticuladas. A liberaÃÃo sequenciada de cloroquina, a partir das microesferas, foi realizada por 2 h em pH 1,2 seguida por uma liberaÃÃo em pH 7,4. A microesfera reticulada liberou 64% da cloroquina em pH 1,2, com um total do fÃrmaco liberado de 92%. O perfil de liberaÃÃo da mesma amostra em pH 7,4 apresenta uma liberaÃÃo controlada do fÃrmaco por cerca de 50 h. NanopartÃculas de QT e CH foram produzidas utilizando como rotas de sÃntese a complexaÃÃo polieletrolÃtica e formaÃÃo de base de Schiff. Na formaÃÃo de complexos polieletrolÃticos parÃmetros como massa molar da quitosana, razÃo molar de carga (n+/n-), ordem de adiÃÃo e concentraÃÃo dos polieletrÃlitos influenciam no tamanho, potencial zeta, Ãndice de polidispersividade e estabilidade das nanopartÃculas em soluÃÃo. O potencial zeta das partÃculas com excesso de QT à positivo e quando se diminui a razÃo molar de carga (n+/n-) para 0,1 o potencial torna-se negativo devido o excesso de chichÃ. Os diÃmetros das nanopartÃculas variaram de 80 a 1200 nm dependendo da concentraÃÃo dos polieletrÃlitos e da quitosana utilizada. NanopartÃculas formadas por quitosana de baixa massa molar (QTb) possuem tamanho maior do que as formadas por quitosana de alta massa molar (QTa). Quando a razÃo de cargas (n+/n-) e a concentraÃÃo dos polieletrÃlitos diminuem o tamanho das nanopartÃculas tambÃm diminui. Na liberaÃÃo da cloroquina em matrizes de CH, QTa e QTb de razÃo 5 e 0,1 duraram cerca 15 dias liberando atà 99% do fÃrmaco, porÃm apenas a razÃo de cargas influenciou no perfil da liberaÃÃo. NanopartÃculas formadas via base de Schiff foram preparadas. A influÃncia de parÃmetros tais como: grau de oxidaÃÃo da goma do chichÃ, massa molar da quitosana, ordem de adiÃÃo e razÃo entre as massas dos polissacarÃdeos foram investigados em relaÃÃo ao tamanho, potencial zeta e estabilidade. O potencial zeta mostrou-se positivo para partÃculas com excesso de QT e negativo para partÃculas com excesso de CH. Os diÃmetros das partÃculas variaram de 30 a 450 nm, dependendo do grau de oxidaÃÃo do CH e da massa molar de QT. Para goma do chichà com menor grau de oxidaÃÃo nanopartÃculas de QTa apresentaram-se maiores do que as formadas por QTb, e para a goma com maior grau de oxidaÃÃo nanopartÃculas de QTb possuÃam maiores tamanhos do que as formadas por QTa. / The aim of this work was the synthesis and characterization of nano and microparticles for malaria drug delivery system. Chitosan microspheres of high molar mass (QTa) and chichà gum (CH) were synthesized by polyelectrolyte complexation and crosslinked with glutaraldehyde. The diameters of the microspheres crosslinked and non-crosslinked were 544  3 μm and 558  2 μm, respectively. The crosslinked beads were not soluble in acidic medium (pH 1.2). The swelling of microspheres was higher in pH 1.2 and that the crosslinked beads have less swelling than non-crosslinked. The sequential release of chloroquine from the microspheres was performed for 2 h followed by a release in pH 7.4. The crosslinked microsphere released 64% of chloroquine at pH 1.2, with a total of drug released of 92%. The release profile of the same sample at pH 7.4 provides a controlled release of the drug for about 50h. QT and CH nanoparticles were prepared using polyelectrolyte complexation and formation of Schiff base. In the formation of polyelectrolyte complex, parameters such as molecular weight of chitosan, the molar ratio of charge (n+/ n-), order of addition and concentration of the polyelectrolyte influence the size, zeta potential, polydispersity index and stability of the nanoparticles in solution. The zeta potential of particles in excess of QT was positive and when the charg molar ratio (n+/ n ) decreases to 0.1 the potential becomes negative due to the excess of CH. The nanoparticles diameters vary from 80 to 1,200 nm depending on the concentration of the polyelectrolyte and the chitosan used. Chitosan nanoparticles formed by a low molecular weight (QTb) were larger than those formed by chitosan of high molecular weight (QTa). The decrease of the charge ratio (n+/n-) and the polyelectrolyte concentrations lead to small size nanoparticle. The release of chloroquine in matrices of CH, QTa and QTb ratio ratio 5 and 0.1 lasted 15 days by releasing up to 99% of the drug, however only the ratio influenced the release profile. Nanoparticles formed by Schiff base reaction were produced. The influence of parameters such as degree of oxidation of CH, chitosan molar mass, addition and masses ration of polysaccharides on size, zeta potential and stability were investigated. The zeta-potential was positive for particles with an excess of QT and negative with excess CH. The particle diameters ranged from 30 to 450 nm, depending on the degree of oxidation of CH and the molar mass of QT. Particle formed with low oxidation of CH and high molar mass chitosan are bigger than those formed with low molar mass chitosan. A inverse behavior was observed when high oxidated CH was used.

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