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Evaluation of in vitro and in vivo potential of siderophores-functionalized liposomes containing moxifloxacin against Mycobacterium tuberculosis

Grant number: 18/02344-2
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2018
Effective date (End): February 28, 2022
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal researcher:Fernando Rogério Pavan
Grantee:Camila Maríngolo Ribeiro
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil


2208/5000According to the World Health Organization (WHO), 10.4 million people developed tuberculosis (TB) in 2016, the infectious disease that kills more people in the world than HIV / AIDS. The factor that aggravates this scenario is the progression of resistant strains of antibiotics available for treatment. One of the factors contributing to the emergence of strains resistant to antibiotics is the low adherence to the treatment, since it is long, toxic and accompanied by adverse effects. In view of this, this project proposes a new approach to drug delivery with the objective of minimizing treatment time and adverse effects by promoting effective delivery of the drug at the site of infection. This strategy for drug delivery is a nanocarrier (liposome) functionalized with siderophores, molecules secreted by bacteria capable of complexing with iron atoms and take them to the bacterium through specific receptors that remain on the bacterial surface. Thus, we believe that a nanocarrier with siderophores on its surface may be able to direct the nanocarriers so that the drug carried is released specifically at the site of infection. The drug chosen to be carried is moxifloxacin, since the anti-Mycobacterium tuberculosis activity is already known and stands out for its effectiveness and safety and is even evaluated in clinical trials to be a first choice drug for the treatment of TB in the future. Three steps are required for this project: 1) The development and characterization of this liposome. For the development, a lipid film hydration technique is proposed and for characterization the determination of the particle size, the polydispersity index, the zeta potential and the analysis of the morphology by transmission electron microscopy. 2) determination of anti-Mycobacterium tuberculosis activity in vitro, determination of minimum inhibitory concentration, bactericidal kinetics, cytotoxicity, intramacrophagic activity and ability to permeate Caco-2 cells as a prediction of intestinal absorption. 3) In a final step, verify the ability of pulmonary bacillary reduction in infected BALB / c mice.

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Scientific publications
(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)
SIMEI AQUARONI, NAYARA AP.; NAKAHATA, DOUGLAS H.; LAZARINI, SILMARA C.; RESENDE, FLAVIA A.; CANDIDO, AMANDA L. P.; BARUD, HERNANE DA SILVA; CLARO, AMANDA MARIA; DE CARVALHO, JOAO ERNESTO; RIBEIRO, CAMILA M.; PAVAN, FERNANDO R.; LUSTRI, BRUNA C.; MACHADO RIBEIRO, TAMARA RENATA; MOREIRA, CRISTIANO G.; CANDIDO, TUANY ZAMBROTI; PASSOS LIMA, CARMEN SILVIA; RUIZ, ANA LUCIA T. G.; CORBI, PEDRO P.; LUSTRI, WILTON R. Antibacterial activities and antiproliferative assays over a tumor cells panel of a silver complex with 4-aminobenzoic acid: Studies in vitro of sustained release using bacterial cellulose membranes as support. Journal of Inorganic Biochemistry, v. 212, NOV 2020. Web of Science Citations: 0.

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