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

作者：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^*; Chorilli Marlus

来源：Molecules, 2015, 20(12): 22534-22545.

DOI：10.3390/molecules201219822

• copper(II) complexes
• antibacterial activity
• Staphylococcus aureus
• Escherichia coli
• nanostructured lipid system

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] center dot nH(2)O ( 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 1,2 1 1,2 1 1 1 -( 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 (R) 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 (R) 25923 and Escherichia coli ATCC (R) 25922, as evaluated by a microdilution technique, and the cytotoxicity index ( IC50') against the Vero cell line ( ATCC (R) CCL- 81TM) were used to calculate the selectivity index ( SI). Among the free compounds, only compound 2 ( MIC 500 mu g/ 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 mu g/ mL, respectively) and S. aureus ( MICs 250, 500 and 125- g/ mL, respectively). The loaded compounds were less toxic against the Vero cell line, especially compound 1 ( IC50 from 109.5 to 319.3 mu g/ 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.

• 出版日期2015-12
• 单位Univ Estadual Paulista