Chemistry, Physics and Technology of Surface

ISSN 2518-1238 (Online), ISSN 2079-1704 (Print)

The processes of adsorption of gemcitabine (GC) on the surface of nanosized singledomain magnetite (Fe₃O₄) have been investigated. Under the experiment conditions, the value of adsorption capacity A was ~ 37.2 mg/g, the extraction extent U (%) – 33.13 %, the separation factor E = 82.58 mL/g. It has been determined that adsorption corresponds to the Freundlich model. The magnetic properties of nanocomposites (NС) Fe₃O₄@GC have been investigated. The average value of the thickness of the adsorbed layer of GC in the composition of Fe₃O₄@GC NC is 2.4±0.1 nm, as evaluated by the method of magnetic granulometry. Magnetic liquids (ML) have been synthesized based on magnetite and physiological solution (PS) stabilized with sodium oleate (Ol.Na) and polyethylene glycol (PEG), which contain GC and antibody (AB) HER2 (Fe₃O₄@GC/Ol.Na/PEG+PS). The properties of ML were investigated as well as cytotoxic/cytostatic activity with respect to HepG2 hepatocellular carcinoma of human liver.

Parameters of ML based on magnetite were found: Fe₃O₄ concentration – 14 mg/mL, Fe₃O₄ particle size –       4–22 nm, average size of Fe₃O₄ particles – 10.8 nm; the average size of Fe₃O₄ particles stabilized with sodium oleate 16.8 nm, saturation magnetization M_∞ = 14.1±2.5 % Gs, hypsometric height – 25±10 % cm, viscosity η = 1.14±3 % mPa·s, density ρ_ML = 1.14 ± 1.0 % g/cm³, the concentration of GC was 1.25 mg/mL, that of HER2 AB was 3.75 μg/mL. We have obtained the calculated and graphic data concerning the dependence of the surface area and the specific magnetization of saturation of Fe₃O₄@GC/Ol.Na/PEG on the thickness of GC layer, which can be useful for predicting of the nanoscale architecture of magnetically sensitive NC and ML in the manufacture of relative drugs. The synergistic nature of the influence of GC/Fe₃O₄/HER2 complex on HepG2 cells was revealed. It has been determined that IC50 for ML is 0.155 mg/mL, in the range of concentration of 0.025–0.1 mg/mL ML it is biocompatible with HepG2 cells. It has been shown that HER2 AB used alone in the investigated concentrations does not affect HepG2 cell viability/proliferation. In vitro, GC inhibits the proliferation of liver carcinoma cells, the IC50 value was 0.02 mg/mL. The use of ML in complex with GC can increase the cytotoxic activity of the composite by 8–10 %. The ML+GC+HER2 AB complexes caused the synergistic effect and an increase in the cytotoxic activity, compared with GC used alone, up to 18–20 %, while GC contents reduced to 0.008 mg/mL.

The results of the studies indicate that the use of ML based on magnetite, gemcitabine, and antibody increases the effectiveness of the antitumor medicines with a significant reduction in their dose and, respectively, the toxico-allergic reactions of the body, and nanosized magnetite can be promising for the manufacture of magnetically sensitive adsorption materials for medical purposes, e.g. for detoxification of an organism after GC therapy.

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