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

Grant number: 13/09265-7
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): July 01, 2013
Effective date (End): September 30, 2015
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal researcher:Marlus Chorilli
Grantee:Patrícia Bento da Silva
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

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.

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Scientific publications (8)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ALEIXO, NADIA ANDRADE; GOMES, PIETRA STEFANY DA SILVA; DA SILVA, PATRICIA BENTO; SATO, MARIANA RILLO; CAMPOS, DEBORA LEITE; BARUD, HERNANE DA SILVA; CASTRO, GUILLERMO RAUL; ISLAN, GERMAN ABEL; TOLEDO, CONSTANZA; KARP, FEDERICO; et al. tudy of antimycobacterial, cytotoxic, and mutagenic potential of polymeric nanoparticles of copper (II) comple. Journal of Microencapsulation, v. 39, n. 1, p. 61-71, . (13/09265-7, 17/16278-9)
SATO, MARIANA R.; OSHIRO JUNIOR, JOAO A.; MACHADO, RACHEL T. A.; DE SOUZA, PAULA C.; CAMPOS, DEBORA L.; PAVAN, FERNANDO R.; DA SILVA, PATRICIA B.; CHORILLI, MARLUS. Nanostructured lipid carriers for incorporation of copper(II) complexes to be used against Mycobacterium tuberculosis. DRUG DESIGN DEVELOPMENT AND THERAPY, v. 11, p. 909-920, . (13/09265-7)
DA SILVA, PATRICIA BENTO; DE FREITAS, EDUARDO SINESIO; BERNEGOSSI, JESSICA; GONCALEZ, MAIRA LIMA; SATO, MARIANA RILLO; FUJIMURA LEITE, CLARICE QUEICO; PAVAN, FERNANDO ROGERIO; CHORILLI, MARIUS. Nanotechnology-Based Drug Delivery Systems for Treatment of Tuberculosis-A Review. JOURNAL OF BIOMEDICAL NANOTECHNOLOGY, v. 12, n. 2, p. 241-260, . (12/19568-4, 13/14957-5, 13/09265-7)
DA SILVA, PATRICIA B.; BONIFACIO, BRUNA V.; FREM, REGINA C. G.; GODOY NETTO, ADELINO V.; MAURO, ANTONIO E.; DA COSTA FERREIRA, ANA M.; LOPES, ERICA DE O.; RADDI, MARIA S. G.; BAUAB, TAIS M.; PAVAN, FERNANDO R.; et al. A Nanostructured Lipid System as a Strategy to Improve the in Vitro Antibacterial Activity of Copper(II) Complexes. Molecules, v. 20, n. 12, p. 22534-22545, . (13/14957-5, 13/09265-7)
DA SILVA, PATRICIA B.; DE FREITAS, EDUARDO SINESIO; SOLCIA, MARIANA CRISTINA; DE SOUZA, PAULA CAROLINA; DA SILVA, MONIZE MARTINS; BATISTA, ALZIR AZEVEDO; EISMANN, CARLOS E.; ROLISOLA, ANA MARTA C. M.; MENEGARIO, AMAURI A.; CARDOSO, ROSILENE FRESSATTI; et al. A Nanostructures Lipid System to Improve the Oral Bioavailability of Ruthenium(II) Complexes for the Treatment of Infections Caused by Mycobacterium tuberculosis. FRONTIERS IN MICROBIOLOGY, v. 9, . (13/14957-5, 13/09265-7)
FONSECA-SANTOS, BRUNO; SILVA, PATRICIA BENTO; RIGON, ROBERTA BALASIN; SATO, MARIANA RILLO; CHORILLI, MARIUS. Formulating SLN and NLC as Innovative Drug Delivery Systems for Non-Invasive Routes of Drug Administration. Current Medicinal Chemistry, v. 27, n. 22, p. 3623-3656, . (13/09265-7, 16/11198-4, 15/05394-2, 14/24180-0, 13/21500-1)
DA SILVA, PATRICIA B.; DE SOUZA, PAULA C.; FIORAMONTI CALIXTO, GIOVANA MARIA; LOPES, ERICA DE O.; FREM, REGINA C. G.; NETTO, ADELINO V. G.; MAURO, ANTONIO E.; PAVAN, FERNANDO R.; CHORILLI, MARLUS. In Vitro Activity of Copper(II) Complexes, Loaded or Unloaded into a Nanostructured Lipid System, against Mycobacterium tuberculosis. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 17, n. 5, . (13/14957-5, 13/09265-7)
DE FREITAS, EDUARDO SINESIO; DA SILVA, PATRICIA BENTO; CHORILLI, MARLUS; BATISTA, ALZIR AZEVEDO; LOPES, ERICA DE OLIVEIRA; DA SILVA, MONIZE MARTINS; FUJIMURA LEITE, CLARICE QUEICO; PAVAN, FERNANDO ROGERIO. Nanostructured Lipid Systems as a Strategy to Improve the in Vitro Cytotoxicity of Ruthenium(II) Compounds. Molecules, v. 19, n. 5, p. 5999-6008, . (13/14957-5, 13/09265-7)

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