The aim of this study was to construct a nanostructured lipid system as a strategy to improve the
in vitro antibacterial activity of copper(II) complexes. New compounds with the general formulae [CuX
2(INH)
2]·nH
2O (X = Cl
− and
n = 1 (
1); X = NCS
− and
n = 5 (
2); X = NCO
− and
n = 4 (
3); INH = isoniazid, a drug widely used to treat tuberculosis) derived from the reaction between the copper(II) chloride and isoniazid in the presence or absence of pseudohalide ions (NCS
− or NCO
−) were synthesized and characterized by infrared spectrometry, electronic absorption spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, elemental analysis, melting points and complexometry with 2,2′,2′′,2′′′-(Ethane-1,2-diyldinitrilo)tetraacetic acid (EDTA). The characterization techniques allowed us to confirm the formation of the copper(II) complexes. The Cu(II) complexes were loaded into microemulsion (MEs) composed of 10% phase oil (cholesterol), 10% surfactant [soy oleate and Brij
® 58 (1:2)] and 80% aqueous phase (phosphate buffer pH = 7.4) prepared by sonication. The Cu(II) complex-loaded MEs displayed sizes ranging from 158.0 ± 1.060 to 212.6 ± 1.539 nm, whereas the polydispersity index (PDI) ranged from 0.218 ± 0.007 to 0.284 ± 0.034. The antibacterial activity of the free compounds and those that were loaded into the MEs against
Staphylococcus aureus ATCC
® 25923 and
Escherichia coli ATCC
® 25922, as evaluated by a microdilution technique, and the cytotoxicity index (IC
50) against the Vero cell line (ATCC
® CCL-81
TM) were used to calculate the selectivity index (SI). Among the free compounds, only compound
2 (MIC 500 μg/mL) showed activity for
S. aureus. After loading the compounds into the MEs, the antibacterial activity of compounds
1,
2 and
3 was significantly increased against
E. coli (MIC’s 125, 125 and 500 μg/mL, respectively) and
S. aureus (MICs 250, 500 and 125 μg/mL, respectively). The loaded compounds were less toxic against the Vero cell line, especially compound
1 (IC
50 from 109.5 to 319.3 μg/mL). The compound
2- and
3-loaded MEs displayed the best SI for
E. coli and
S. aureus, respectively. These results indicated that the Cu(II) complex-loaded MEs were considerably more selective than the free compounds, in some cases, up to 40 times higher.
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