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-salenBr₂) has shown excellent preliminary results against different cell lines; however, its poor water solubility is a major drawback for the use of Cu-salenBr₂ in biological fluids. In order to overcome this limitation, Cu-salenBr₂ 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 (Cu-salenBr₂/copolymer) formulation for intravenous application. The Cu-salenBr₂ formulations were characterized by UV–vis 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-salenBr₂ 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-salenBr₂ 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-salenBr₂ solubilized in DMSO/DMEM and Cu-salenBr₂/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-salenBr₂/P-123 formulation were 0.41 and 1.6 μmolL⁻¹ for spleen and COS-7 cells, respectively.