Influence of magnetite incorporation into chitosan on the adsorption of the methotrexate and in vitro cytotoxicity

Abstract

Emerging pollutants are a group of substances involved in environmental contamination resulting mostly from incomplete drug metabolism, associated with inadequate disposal and ineffective effluent treatment techniques. Methotrexate (MTX), for instance, is excreted at high concentrations in unchanged form through the urine. Although the MTX is still effective in cancer and autoimmune disease treatment, this drug shows the ability of bioaccumulation and toxicity to the organism. Thus, the present work aimed to evaluate the adsorption of the MTX drug onto magnetic nanocomposites containing different amounts of incorporated magnetite (1:1, 1:5, and 1:10 wt%), combining the theoretical-experimental study as well as the in vitro cytotoxicity. Moreover, equilibrium studies (Langmuir, Freundlich, Temkin, Dubinin-Radushkevich, Hill, Redlich-Peterson, and Sips), kinetic (PFO, PSO, and IPD), and thermodynamic (ΔG°, ΔH°, and ΔS°) were used to describe the experimental data, and ab initio simulations were employed in the theoretical study. Magnetic nanocomposites were synthesized by the co-precipitation method using only FeCl₂ as the iron precursor. Adsorbents were characterized by FTIR, XRD, Raman, SEM-EDS, BET, and VSM analysis. Meanwhile, cytotoxic effects on L929 and A375 cell lines were evaluated through MTT, NR, and LDH assays. The adsorption of the MTX was carried out in a typical batch system, exploring the different experimental conditions. The theoretical study suggests the occurrence of chemisorption between CS·Fe₃O₄-MTX. The maximum adsorption capacity of MTX was 285.92 mg g^-1, using 0.125 g L^-1 of CS·Fe₃O₄ 1:1, with an initial concentration of the MTX (50 mg L^-1), pH 4.0 at 293 ± 1.00 K. The best adjustment of equilibrium and kinetic data were the Sips (low values for statistical errors) and PSO (q_e = 96.73 mg g^-1) models, respectively. Thermodynamic study shows that the adsorption occurred spontaneously (ΔG° < 0), with exothermic (ΔH° = - 4698.89 kJ mol^-1) and random at the solid-solution interface (ΔS° = 1,476,022.00 kJ mol^-1 k^-1) behavior. Finally, the in vitro study shows that magnetic nanomaterials exhibit higher cytotoxicity in melanoma cells. Therefore, the magnetic nanocomposite reveals to be not only an excellent tool for water remediation studies but also a promising platform for drug delivery.

Keywords: DFT study; Magnetic bionanoadsorbents; Melanoma; Methotrexate; Water decontamination.