Copolymers as nanocarries of griseofulvin: studies of the solubilisation, drug release and cytotoxicity in human neutrophil

• Autor(a) principal: Samira AssunÃÃo de Oliveira
• Data de Publicação: 2012
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UFC
• Texto Completo: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=13105
• topic: copolÃmeros em bloco; solubilizaÃÃo de fÃrmacos; griseofulvina, carreadores; neutrÃfilo; block copolymer; drug solubilization; griseofulvin; drug delivery; neutrophil; QUIMICA

The low solubility of griseofulvin in water (1.4 and 1.95 mg/dL at 25 and 37 ÂC, respectively) is a limiting factor for its administration. Despite of this, micellar solutions prepared with copolymers are being used to increase the solubility of these drugs. In addition, these mixtures of surfactants have low toxicity, are efficient in the dilution process and present high potential as carriers of insoluble drugs. These factors are the main reason for the interest in the research of these copolymers. This project proposes the investigation of the use of copolymers P123 (E21P67E21), E45S8 (denominated S8) and E45S17 (denominated S17) and their mixtures to obtain higher solubility of the drug griseofulvin through the method of direct dilution. The project also aims to investigate of the potential of these systems as a drug carrier model for griseofulvin through the study of cytotoxicity of these carriers through human neutrophil, the study of the gelation properties of the two diblocks S8 and S17 and its mixtures with triblock P123 in the proportion of 50/50 and 30/70. To determine the critical micelle concentration (cmc) the method of dye solubilisation was used to measure the fluorescence. The solubility of the drug griseofulvin in the micellar systems was quantified by UV-Vis spectrophotometer and by 1H NMR. The systems with pure S17 and with encapsulated griseofulvin were characterised by infrared spectroscopy and through x-ray diffraction. Experiments of drug release in vitro were carried out with the best encapsulating systems or carriers. The copolymers S8 and S17 and their mixtures with the P123 showed to be promising for the administration of hydrophobic drugs as they presented low toxicity and excellent values for solubilisation capacity (Scp). The mixtures P50/S8 and P50/S17 at 37 oC were the ones that presented the best results of Scp with equally low values of cmc, therefore showing the efficiency of these micellar systems as carriers of the drug griseofulvin.