Evaluation of the potential nanostructured lipid systems for administration of Cu(II) compounds applicable in optimizing the treatment of tuberculosis

Abstract

Tuberculosis (TB) is the main infectious disease of bacterial origin in the world, taking of annual death of people thousands and causing economic losses overall approximately 12 billion dollars per year. No specific drug against this disease has been developed since 1960 and the emergence of multidrug-resistant TB cases makes the ineffectiveness of current treatment. The íon Cu (II) has a tendency to form complexes with other molecules, forming coordination compounds with different activities, among them antimicrobial. Nanostructured lipid systems, such as microemulsions (MEs) have gained prominence in the field of pharmaceutical sciences by reason of improve the solubility and stability of pharmaceuticals, in addition to providing prolonged action and can carrier substances with different degrees of hydrophilicity / lipophilicity in the same formulation. This work aims to develop and characterize MEs containing coordination compounds of copper (II) and carry out in vitro and in vivo biological assays against Mycobacterium tuberculosis. Complexes of Cu (II) containing isoniazid (INH), a drug widely used to treat TB, were developed and characterized during the doctoral thesis of candidate. Since such compounds showed low water solubility, compromising their biopharmaceutical properties and made it unfeasible to in vivo assay, such compounds will be incorporated into in this project MEs, which are characterized by dynamic light scattering, polarized light microscopy, zeta potential, rheological behavior, small-angle X-ray (SAXS) and thermal analysis. As for in vitro biological assays will be determined the minimum inhibitory concentration (MIC) and carried out the kinetics the study of the compounds against M. tuberculosis, as well as the cytotoxicity test. In vivo assays evaluation of acute toxicity and oral bioavailability in mice will also be carried out. Expected to thereby obtain a nanostructural level system that can optimize the use of complexes of Cu (II) in TB therapy.