Non-invasive image-guided brain access with gradient propulsion of magnetic nanoparticles

The blood-brain barrier (BBB) provides natural protection to the central nervous system against noxious substances but also prevents access to therapeutics. Previously-investigated strategies for introducing drugs into the brain have included disruption of the BBB through energy deposition (RF, ultrasound), and diffusion from brain injections (along nonvascular routes) directly into the brain parenchyma. Magnetic gradients can increase transport rates of nanoparticle ferrofluids. As an example, we and others have shown significant increases in transport of drug-coated magnetic nanoparticles across the round window membrane [1]. Transport of chemicals across the cribiform plate (that separates the nasal cavity from the intracranial compartment) and into the brain is used naturally for olfaction, and by drug users (both legal and illicit). In pilot animal studies, we have shown that transport of magnetic nanoparticles can be dramatically increased across the cribiform plate into the brain olfactory bulb, through the application of magnetic gradients on the order of 0.5 T/cm. The increased concentrations of nanoparticles were easily detected with 4.7 T MRI systems. Transport of ferrofluid was observed from the posterior brain to the olfactory bulb under the influence of similar gradients. Such high magnetic gradients could be implemented through custom coils to effect MRI guidance, with minimal bioeffects if ramped up quickly [2]. These levels of gradients are easily realized in either a classic pull magnet configuration or with a Halbach push magnet array, with the push conferring additional flexibility as compared to standard approaches [3]. Additional studies are underway to exploit the use of drug-coated magnetic nanoparticles to gain entry in the central nervous system via natural entry-ways. Potential applications include delivery of drugs for the amelioration of epilepsy, motor and behavior/addictive disorders and to combat infectious diseases.