Nanostructured lipid carriers for incorporation of copper(II) complexes to be used against Mycobacterium tuberculosis.

Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis. Cessation of treatment before the recommended conclusion may lead to the emergence of multidrug-resistant strains. The aim of this study was to develop nanostructured lipid carriers (NLCs) for use in the treatment of M. tuberculosis. The NLCs comprised the following lipid phase: 2.07% polyoxyethylene 40 stearate, 2.05% caprylic/capric triglyceride, and 0.88% polyoxyl 40 hydrogenated castor oil; the following aqueous phase: 3.50% poloxamer 407 (F1-F6), and 0.50% cetyltrimethylammonium bromide (F7-F12); and incorporated the copper(II) complexes [CuCl2(INH)2]·H2O (1), [Cu(NCS)2(INH)2]·5H2O (2), and [Cu(NCO)2(INH)2]·4H2O (3) to form compounds F11.1, F11.2, and F11.3, respectively. The mean diameter of F11, F11.1, F11.2, and F11.3 ranged from 111.27±21.86 to 134.25±22.72 nm, 90.27±12.97 to 116.46±9.17 nm, 112.4±10.22 to 149.3±15.82 nm, and 78.65±6.00 to 122.00±8.70 nm, respectively. The polydispersity index values for the NLCs ranged from 0.13±0.01 to 0.30±0.09. The NLCs showed significant changes in zeta potential, except for F11.2, with F11, F11.1, F11.2, and F11.3 ranging from 18.87±4.04 to 23.25±1.13 mV, 17.03±1.77 to 21.42±1.87 mV, 20.51±1.88 to 22.60±3.44 mV, and 17.80±1.96 to 25.25±7.78 mV, respectively. Atomic force microscopy confirmed the formation of nanoscale spherical particle dispersions by the NLCs. Differential scanning calorimetry determined the melting points of the constituents of the NLCs. The in vitro activity of copper(II) complex-loaded NLCs against M. tuberculosis H37Rv showed an improvement in the anti-TB activity of 55.4, 27.1, and 41.1 times the activity for complexes 1, 2, and 3, respectively. An in vivo acute toxicity study of complex-loaded NLCs demonstrated their reduced toxicity. The results suggest that NLCs may be a powerful tool to optimize the activity of copper(II) complexes against M. tuberculosis.

Vanadium Complexes with Hydrazone or Thiosemicarbazone Ligands as Potential Anti-Mycobacterium tuberculosis Agents.

Tuberculosis (TB) is an infectious disease caused mainly by Mycobacterium tuberculosis (MTB) and still an important public health problem worldwide. Some factors like the emergence of multidrug resistant (MDR) and extensively drug-resistant (XDR) strains make urgent the research of new active compounds. Searching for new inorganic compounds against TB, three new dioxovanadium(V) complexes were obtained upon reaction of [VO(acac)2] with hydrazone and thiosemicarbazone ligands derived from di-2-pyridyl ketone. Spectroscopic studies and X-ray crystallography revealed asymmetrically oxo bridged binuclear complexes of the type [{VO(L(1,2))}2(µ-O)2], involving the hydrazone ligands, while a mononuclear square pyramidal complex of the type [VO2(L(3))] was formed with the thiosemicarbazone ligand. The compounds were tested against M. tuberculosis and three of them, with MICs values between 2.00 and 3.76 µM were considered promising for TB treatment. Such MIC values are comparable or better than those found for some drugs currently used in TB treatment.