Nanoencapsulação de compostos de rutênio, análise de sua atividade anti - Mycobacterium tuberculosis e biodisponibilidade oral

• Autor(a) principal: Freitas, Eduardo Sinesio de [UNESP]
• Data de Publicação: 2015
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://hdl.handle.net/11449/139385; http://www.athena.biblioteca.unesp.br/exlibris/bd/cathedra/31-05-2016/000858669.pdf
• topic: Mycobacterium tuberculosis; Tuberculose; Citotoxicidade; Química bioinorgânica; Cytotoxicity

Tuberculosis (TB) is an infectious airborne disease, curable and mainly affects the lungs. In recent years, the death rate has been decreasing, however, resistant strains and co-infection TB / HIV have hampered the disease control efforts, leading to increased mortality. Another troubling factor is that one third of the world's population is infected with Mycobacterium tuberculosis (MTB) in a state of latency, which serves as a reservoir for active TB. In an effort to remedy this failure, it is increasing the importance of bioinorganic chemistry as an ally in the new anti-TB drug research. The Ruthenium (Ru) is a chemical element that has the capacity to mimic the iron (Fe) in our body, with low toxicity and able to form stable complexes, this element has been studied since the 80's as a possible substitute for platinum (Pt ), the central metal structure of cisplatin used in anticancer treatments. In previous studies involving heteroleptic ruthenium complexes: [Ru(pic)(dppb)(bipy)]PF6 (SCAR1); [Ru(pic)(dppb)(Me-bipy)]PF6 (SCAR2); [Ru(pic)(dppb)(phen)]PF6 (SCAR4); cis-[Ru(pic)(dppe)2]PF6 (SCAR5); cis[RuCl2(dppb)(bipy)] (SCAR6) and [Ru(pic)(dppe)(phen)]PF6 (SCAR7), we observed an excellent anti-TB activity, moderate cell toxicity and lack of oral bioavailability in vivo model of these complexes thus the main objective of this study was to evaluate the toxicity and oral bioavailability of those nano-coated complexes. These nanostructured systems have been developed using different ratios of surfactant (soybean phosphatidylcholine, Emulgin® and sodium oleate), aqueous phase (phosphate buffer pH 7.4) and oil (cholesterol) in order to obtain a system for incorporating the compounds of ruthenium. The system was characterized by analyzes rheology, particle size and zeta potential. The anti-TB activity of the compounds was determined by the microdilution assay with Resazurin (REMA) compared to strains of M. tuberculosis H37Rv and clinical isolates...