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Molecules 2015, 20(12), 22534-22545;

A Nanostructured Lipid System as a Strategy to Improve the in Vitro Antibacterial Activity of Copper(II) Complexes

School of Pharmaceutical Sciences, UNESP—University Estadual Paulista, Campus Araraquara, Araraquara, 14801-902 São Paulo, Brazil
Chemistry Institute, UNESP—University Estadual Paulista, Campus Araraquara, Araraquara, 14800-060 São Paulo, Brazil
Chemistry Institute, USP—University São Paulo, Campus São Paulo, São Paulo, 05508-900 São Paulo, Brazil
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Academic Editor: Peter J. Rutledge
Received: 30 October 2015 / Revised: 23 November 2015 / Accepted: 24 November 2015 / Published: 16 December 2015
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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 [CuX2(INH)2]·nH2O (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 (IC50) against the Vero cell line (ATCC® CCL-81TM) 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 (IC50 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. View Full-Text
Keywords: copper(II) complexes; antibacterial activity; Staphylococcus aureus; Escherichia coli; nanostructured lipid system copper(II) complexes; antibacterial activity; Staphylococcus aureus; Escherichia coli; nanostructured lipid system

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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da Silva, P.B.; Bonifácio, B.V.; Frem, R.C.G.; Godoy Netto, A.V.; Mauro, A.E.; Ferreira, A.M.C.; Lopes, E.O.; Raddi, M.S.G.; Bauab, T.M.; Pavan, F.R.; Chorilli, M. A Nanostructured Lipid System as a Strategy to Improve the in Vitro Antibacterial Activity of Copper(II) Complexes. Molecules 2015, 20, 22534-22545.

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