Guidance of Magnetic Nanocontainers for Treating Alzheimer's Disease Using an Electromagnetic, Targeted Drug-Delivery Actuator.

Abstract

The "impermeability" of the blood-brain barrier (BBB) has hindered effective treatment of central nervous system (CNS) disorders such as Alzheimer's disease (AD), which is one of the most common neurodegenerative disorders. A drug can be delivered to a targeted disease site effectively by applying a strong electromagnetic force to the conjugate of a drug and magnetic nanocontainers. This study developed a novel nanotechnology-based strategy to deliver therapeutic agents to the brain via the BBB as a possible therapeutic approach for AD. First, a novel approach for an electromagnetic actuator for guiding nanocontainers is introduced. Then, we analyzed the in vivo uptake in mice experimentally to evaluate the capacity of the nanocontainers. In the mouse model, we demonstrated that magnetic particles can cross the normal BBB when subjected to external electromagnetic fields of 28 mT (0.43 T/m) and 79.8 mT (1.39 T/m). Our study also assessed the differential effects of pulsed (0.25, 0.5, and 1 Hz) and constant magnetic fields on the transport of particles across the BBB in mice injected with magnetic nanoparticles (MNPs) via a tail vein. The applied magnetic field was either kept constant or pulsed on and off. Relative to a constant magnetic field, the rate of MNP uptake and transport across the BBB was enhanced significantly by a pulsed magnetic field. Localization inside the brain was established using fluorescent MNPs. These results using 770-nm fluorescent carboxyl magnetic nanocontainers demonstrated the feasibility of the proposed electromagnetic targeted drug delivery actuator. These results establish an effective strategy for regulating the biodistribution of MNPs in the brain through the application of an external electromagnetic field. This might be a valuable targeting system for AD diagnosis and therapy.