Modeling of adsorption and release kinetics of methotrexate from thermo/magnetic responsive CoFe2O4–BaTiO3, CoFe2O4–Bi4Ti3O12 and Fe3O4–BaTiO3 core-shell magnetoelectric nanoparticles functionalized with PNIPAm

Abstract

From a pharmaceutical point of view, due to their magnetic and electric properties, novel magnetoelectric core-shell nanoparticles are a promising drug nanocarrier that will improve the efficiency of several therapies through the selective permeation of drugs on a specific cell population based on their cell membrane potential. The performances of previously synthesized CoFe2O4–BaTiO3, CoFe2O4–Bi4Ti3O12 and Fe3O4–BaTiO3 core-shell type magnetoelectric nanoparticles functionalized with PNIPAm were evaluated as potential drug nanocarriers by adsorption and release kinetics studies with methotrexate as model drug. Mathematical modeling allowed the comprehension of the overall phenomena affecting drug adsorption and release kinetics. In both cases, the physicochemical parameters and the underlying thermodynamic assumptions associated with models provided an insight into adsorption and release mechanisms, surface properties, and affinity degree. According to the kinetics adsorption studies the methotrexate adsorption was limited by the accessibility to surface at interparticle sites. Additionally, “L” type adsorption isotherms indicated multiple layer formation, the cooperative adsorption of methotrexate molecules and their homogenous surface distribution. Freundlich model was the best describing methotrexate adsorption phenomenon.Special focus was given to nanoparticles stability on dispersion effects over adsorption efficiency by submitting or not the nanoparticles to 1-min initial sonication at the beginning of adsorption process, affording important mechanistic insights. The maximum methotrexate adsorption was achieved at concentrations near the saturation submitted to sonication.Thereupon, the subsequent consequences of changes of surface area during methotrexate adsorption was observed in release profiles. Fascinating release profiles were observed from MENs submitted to different conditions of temperature, (25 or 40 °C), methotrexate loaded amount, and the application of a magnetic field due to surface area fluctuations during methotrexate adsorption. Rregardless their composition, the nanoparticles shown the same physicochemical behavior, manifested as comparable drug release profiles. The nanoparticles demonstrated sensibility to both, temperature and alternating magnetic fields stimuli, nevertheless the overall drug release was achieved only under the effects of magnetic stimulus. Methotrexate interparticle-localized resulted in an incomplete release at temperatures below and above PNIPAm lowest critical solution temperature. In summary, these nanocarriers shown a good in vitro performance, so a suitable in vivo behavior is expected.