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| Author(s): |
Débora Braga Vieira
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) |
| Defense date: | 2008-04-15 |
| Examining board members: |
Ana Maria Carmona Ribeiro;
Iolanda Midea Cuccovia;
Carlos Frederico Martins Menck;
Shirley Schreier;
Marcel Tabak
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| Advisor: | Ana Maria Carmona Ribeiro |
| Abstract | |
The formation, colloid stability and activity in vitro against Candida albicans of several supramolecular assemblies composed of drug, cationic lipid and/or polyelectrolytes were systematically evaluated by means of dynamic light scattering for particle sizing, zeta- potential analysis, UV-visible spectroscopy, effect of drug on gel-to-liquid-crystalline phase transition of the cationic bilayer and determination of drug loading. Supramolecular assemblies of antifungal drugs such as miconazole and amphotericin B were obtained by solubilization of the drugs in cationic bilayer fragments composed of dioctadecyldimethylammonium bromide or coverage of drug particles with a layer of the quoted cationic lipid. As a model of anticancer drug, cisplatin was sandwiched between two oppositely charged polyelectrolytes: chitosan and carboxymethylcellulose. Cisplatin induced reduction in particle size acting as a cross-linker between polyelectrolytes. For amphotericin B, at low and high molar proportion drug to cationic lipid, similar supramolecular assemblies were coated by polyelectrolytes such as carboxymethylcellulose, poly(diallyldimethylammonium) and polylysine yielding cationic nanoparticles that presented optimal colloid stability and fungicidal activity. Miconazole became attached at the hydrophobic edges of bilayer fragments at room temperature and/or, upon an increase in temperature, inserted in the bilayer core. Curiously, this last formulation in the cationic lipid yielded a synergistic action against Candida albicans. Dioctadecyldimethylammonium bromide (DODAB) is an excellent antimicrobial agents per se. Its mechanism of antimicrobial action was compared to the one for hexadecyltrimethylammonium bromide (CTAB). Adsorption of these compounds on the cells decreased going from CTAB to DODAB bilayer fragments and to large vesicles. Absence of leakage of small phosphorylated compounds, proteins or DNA from fungus indicated a mechanism of action different from cell lysis. Adsorption of the cationic compounds changed the sign of the cell zeta-potential from negative to positive. There was a clear relationship between positive charge on fungus and death. (AU) | |