An Alternating Magnetic Field-Controlled Drug Delivery System Based on 4,4′-Azobis (4-cyanovaleric Acid)-Functioned Fe3O4@Chitosan Nanoparticles

Abstract

Herein, we designed chitosan–coated Fe3O4 nanocomposites for the control release of drugs by an alternating magnetic field (AMF). The chitosan-coated Fe3O4 nanoparticles (Fe3O4@CS) were prepared by a alkaline co-precipitation method, and then, the model drug toluidine blue (TB) was covalently grafted onto the surface of the nanocomposite by a two-step amide reaction with the thermosensitive molecule 4,4′-azobis (4-cyanovaleric acid) (ACVA) as the linker group. The prepared nanocomposites were superparamagnetic and showed high magnetization saturation (about 54.0 emu g−1). In vitro hydrothermal release studies showed that most parts of the TB would be effectively enclosed within the nanocarriers at lower ambient temperatures (23 or 37 °C) due to the molecular bonding of ACVA. The results of kinetic fitting of hydrothermal release data showed that TB released from nanoparticles followed first-order kinetics (R2 > 0.99) and the Korsemeyer–Peppas model (R2 > 0.99, n < 0.5). Most importantly, a single magnetron release experiment demonstrated an approximately linear relationship between the cumulative release of the drug and the duration of action of AMF (R2 = 0.9712). Moreover, the increase in the cumulative release of the drug can be controlled by controlling the switch of the AMF generation device. Therefore, the ACVA-modified Fe3O4@CS nanocarrier designed in this study is a promising model for drug delivery that enables the control of drug release dose by AMF.