Interactions between copper(II) dibrominated salen complex and copolymeric micelles of P-123 and F-127

Metal-salen complexes have been extensively studied for several applications in nanomedicine as chemotherapic agents substituting, for example, cisplatin based compounds. A recently synthesized copper(II) dibrominated salen complex (Cu-salenBr(2)) has shown excellent preliminary results against different cell lines; however, its poor water solubility is a major drawback for the use of Cu-salenBr(2) in biological fluids. In order to overcome this limitation, Cu-salenBr(2) was incorporated in biocompatible micellar systems of Pluronics surfactants F-127 and P-123 by the solid dispersion method, aiming at both the increase in the bioavailability of the complex and the development of a(CusalenBr(2)/copolymer) formulation for intravenous application. The Cu-salenBr(2) formulations were characterized by UVvis and infrared spectroscopies; this has been complemented by studies on the effect of concentration on the self-diffusion coefficients of micelles. The encapsulation efficiency and the thermal and kinetics stability of Pluronic-Cu-salenBr(2) formulations were studied. From these studies, it has been found that P-123-containing formulations are more stable and, consequently, they were chosen for cytotoxicity studies. The cytotoxicity of Cu-salenBr(2) against fibroblast-like kidney cells (COS-7) and BALB/c mice spleen cells was evaluated, either alone or incorporated in P-123. No significant cytotoxicity was observed for Cu-salenBr(2), per se, dissolved in the culture medium, however, Cu-salenBr(2) solubilized in DMSO/DMEM and Cu-salenBr(2)/P-123 formulation showed a concentration dependent toxic effect on both COS-7 cell line and mouse spleen cells. The IC50 values obtained for the Cu-salenBr(2)/P-123 formulation were 0.41 and 1.6 molL(-1) for spleen and COS-7 cells, respectively. (C) 2017 Elsevier B.V. All rights reserved.