Magnetic layered double hydroxides with carbamazepine for breast cancer treatment

M Florencia Peralta; Silvia N Mendieta; I Romina Scolari; M Verónica Gerbaldo; Marcos I Oliva; Germán A Gil; Gladys E Granero; Mónica E Crivello

doi:10.1016/j.heliyon.2023.e21030

Magnetic layered double hydroxides with carbamazepine for breast cancer treatment

Heliyon. 2023 Oct 14;9(10):e21030. doi: 10.1016/j.heliyon.2023.e21030. eCollection 2023 Oct.

Authors

M Florencia Peralta¹, Silvia N Mendieta¹, I Romina Scolari², M Verónica Gerbaldo¹, Marcos I Oliva³, Germán A Gil⁴, Gladys E Granero², Mónica E Crivello¹

Affiliations

¹ Centro de Investigación y Tecnología Química (CITeQ), UTN-CONICET, Av. Cruz Roja Argentina y Maestro López, Córdoba, 5000, Argentina.
² Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), UNC-CONICET, Departamento de Ciencias Farmacéuticas, Universidad Nacional de Córdoba, Av. Medina Allende S/N, Córdoba, 5000, Argentina.
³ Instituto de Física Enrique Gaviola (IFEG), UNC-CONICET, Facultad de Matemática, Astronomía, Física y Computación, UNC, Av. Medina Allende S/N, Córdoba, 5000, Argentina.
⁴ Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), UNC-CONICET, Av. Haya de la Torre S/N, Córdoba, 5000, Argentina.

Abstract

Current cancer chemotherapy is associated with many side effects and, in some cases, drug resistance, which makes the search for new active molecules and drug delivery strategies imperative. Carbamazepine is an antiepileptic compound that has shown efficacy against breast cancer cell lines. In this study, it was incorporated into layered double hydroxide nanoclays, the percentage of drug loading was increased compared to previous research, and the clays were impregnated with magnetic Fe₃O₄ nanoparticles. The goal of the magnetic Fe₃O₄-impregnation was to direct the nanocomposites to the therapeutic target with an external magnetic field. The nanoclay-carbamazepine composites had a carbamazepine loading of 51 %, and the nanoclay-carbamazepine-nanoparticles had a drug loading of 13 % due to the addition of more ingredients. The structure of the composites was analyzed by X-ray diffraction and Scherrer equation, showing a layered double hydroxide organization with crystal sizes of 9-15 nm; from transmission electron microscopy, the final compounds showed a particle size of 97-158 nm, small enough for systemic circulation. In vibrating sample magnetization studies, the composites showed a superparamagnetic behavior with high magnetic saturation (9-17 emu/gr), which should allow a good material attraction by an external magnetic field located near the tumor. In vitro drug release studies were done in Franz cells and measured by UV/Vis spectrophotometry; they showed that carbamazepine release from the nanocomposites responds to the media pH: a good drug release at the lysosome pH and slow release at the blood pH. Finally, the efficacy was tested in vitro in MDA-MB-231 breast cancer cells, and the composites showed an enhanced efficacy in comparison with that produced by the free drug (96 % and 62 % of cell inhibition respectively). Carbamazepine administered with magnetic clays as a carrier is a promising treatment for breast cancer, and further studies should be done to measure the arrival time and the efficacy in vivo.

Keywords: Cancer therapy; Carbamazepine; Layered double hydroxide; Nanoclay; Nanoparticle.