Oct 15, 2009
Field gradient guides nanoparticles through biological fluid
The challenge of drug delivery to the brain is unique. In part, this is due to the intricate organizational structure of the brain that can be compared to a multi-organ interacting parallel processing neural net with anatomical parcellation allowing performance of activities consistent with the complexity of being human. The challenge is also due to the unique partition of the brain and its vulnerable neural cellular components from the blood stream through the blood brain barrier (BBB).
The BBB significantly limits mass transport to the brain especially for hydrophilic small molecules and also larger molecules such as peptides, proteins and genes. This may uniquely limit the ability of the physician to selectively target currently available drugs in neurological disorders.
Researchers in the US and Canada with expertise in nanochemistry (V Yathindranath and T Hegmann), condensed matter physics (J van Lierop), imaging (K Potter and C B Fowler), neurological medicine and pharmacology (D Miller and D F Moore) have teamed up to provide a preliminary step in knowledge integration to translate the evolving field of nanoscience into drug delivery systems particularly with brain therapeutics in mind.
Briefly, the work describes the mass transport of bovine serum albumin (protein) attached to iron-oxide core–shell nanoparticles (IO cs-NPs) in vitro (agarose gel) and in an egg as a model system for a biological fluid, under a magnetic gradient field followed by visualization using MRI.
The study may form the proof of principle for directed drug delivery to specific brain regions by facilitating understanding of mass convection through a complex media and the BBB. A planned extension of the work is to direct IO cs-NPs using 3-D stereotactic alignment with orthogonal oscillating Helmholtz coils magnetic gradients allowing for both translational and directional mass transport together with temporal-spatial focusing of the drug delivery vector.
Using this approach, it might be possible to deliver large peptide molecules such as growth factors to injured brain regions or genes for gene therapy of inherited metabolic disorders such as Gaucher disease Type II, a particularly malignant neuronopathic form of Gaucher disease.
The team presented its work in Nanotechnology.
About the authors
The work was performed at the University of Manitoba (Winnipeg, MB), the Defense and Veterans Brain Injury Center, DVBIC (Walter Reed Army Medical Center, Washington, DC), and the Traumatic Brain Injury Research Center at the Armed Forces Institute of Pathology (Rockville, MD). Vinith Yathindranath is a Ph.D. student studying Chemistry at the University of Manitoba under the joint supervision of Drs Hegmann, van Lierop and Moore. Dr Hegmann is an Associate Professor at the Department of Chemistry and Dr van Lierop is an Associate Professor at the Department of Physics & Astronomy, both at the University of Manitoba. Dr Kimberlee Potter is the Technical Director, Magnetic Resonance Microscopy Facility and Dr Carol. B. Fowler, Research Associate, is post-doctoral faculty, both at the Department of Biophysics (Armed Forces Institute of Pathology). Dr David F. Moore is Deputy Director for Research (DVBIC), Lead of the Laboratory of Traumatic Brain Injury, and a Visiting Scientist at the MIT Institute of Soldier Nanotechnology.