Analysis of the antifungal activity of new formulations of voriconazole

Identifier:  TFG:2133

Handle: https://hdl.handle.net/20.500.11797/TFG2133

Authors:  Dolader Ballesteros, Elena

Abstract:
Fungi are eukaryotic organisms with applications both in the biotechnology industry and in the ecological field. In spite of presenting these characteristics, the last two decades it has increased the amount of fungal infections due to the emerging opportunistic pathogens. The genus most isolated in the clinic are Candida and Aspergillus. Currently, the treatment of this type of infections is limited to the low variety of antifungals, the few therapeutic targets, the toxicity of the drugs and the mechanisms of resistance of the species. The triazoles, the azoles of second generation, are the most used antifungals nowadays. Voriconazole is the first therapeutic resource used to treat aspergillosis and some types of candidiasis. This drug has a wide range of application and is easy to administer orally but has certain limitations: hepatotoxicity and variable pharmacokinetics and biodistribution. The new formulations of voriconazole analyzed in the study, are able to form polymeric micelles systems that keep voriconazole in its hydrophobic core. In addition to the permeability and solubility of the compound, micellar systems can alter pharmacokinetics and biodistribution and modulate the toxicity of the drug. Therefore, the new formulations can increase the efficacy of voriconazole in fungal infections. In this study, an analysis of the in vitro activity, biodistribution, toxicity and efficacy of the new formulations was developed. Although there was no significant difference in in vitro antifungal activity, the biodistribution of one of the formulations showed a reduction in liver toxicity compared to voriconazole. Keywords: opportunistic pathogens; Candida; Aspergillus; voriconazole; toxicity; biodistribution; polymeric micelles.