Magnetically-Guided Nanoparticle Drug Delivery Seth Baker, RET Fellow 2011 Percy Julian Middle School RET Mentor: Prof. Andreas A. Linninger Chicago Science Teacher Research (CSTR) Program – NSF-RET 2011 Magnetite NanoparticlesIntroduction Conclusion Experimental Design Testing Magnetic Susceptibility Future Studies Acknowledgements Motivation Direct application for improved medical treatments of neurological disorders - Alzheimer’s, Parkinson’s, autism, cerebrovascular disease, abnormal vascular structures (tumors), and stroke conditions. Improved pharmacokinetics and pharmacodynamics - Limiting therapeutics to targeted sites reduces systemic distribution/toxicity - Targeted delivery can lower dosage and reduce cytotoxicity Objective Many therapeutic drugs for treatment of neurological conditions can cause systemic toxicity due to limited targeting of effected tissue. Magnetically- guided drug delivery offers treatment options that can reach site specific areas of the brain. Testing is needed to determine a standard protocol for infusing and guiding nanoparticles. Use of agarose brain phantoms can eliminate preliminary animal testing. cerebral artery Magnetic nanoparticles indicate some attraction toward a magnet during capillary experiments in agarose gel brain phantoms. Step design for polymer catheters can reduce reflux during convection enhanced delivery of nanoparticles. Larger diameter nanoparticles tend to agglomerate more rapidly than smaller diameter particles. Capillary experiment set up with 1.0 ml syringe and 30 nm magnetite Convection Enhanced Delivery Step Catheters 30 nm magnetite particles delivered on rat brain tissue to determine susceptibility to nanoparticles. Rat Brain Tests Results Coronal slices of rat brain after placed in Prussian blue dye to determine untreated brain susceptibility to staining mm diameter step catheter tip 173 pound pull force magnet under capillary infused agarose gel Coronal slices of rat brain showing distribution profile of Prussia blue dye. 30 nanometer Magnetite particles above a 173 pound pull force magnet at 4 minutes 30 nanometer Magnetite particles above a 173 pound pull force magnet at 8 minutes 30 nanometer Magnetite particles above a 173 pound pull force magnet at 0 minutes  New Era Pump System syringe pump  Polyethylene tubing (various gauges)  Polymer step catheters (various gauges)  1.0 ml medical syringes  Magnetic nanoparticles (various diameters)  Sodium Hydroxide  Magnets of various pull force  0.6% Agarose gel  Prussian Blue Stain  Plastic cell blocks  Surfactants  Glass slides for slicing gel  Canon EOS Rebel Xti  Rat brain tissue Capillary Experiments 35 and 173 pound pull force magnets affect on capillary experiment Improved infusion of magnetic nanoparticles Studying various techniques to reduce the agglomeration of magnetic nanoparticles through the use of various surfactants as well as various catheter design, tube diameters, and nanoparticle concentrations. Rat brain infusion Improve methods of introducing magnetic nano- particles into fresh brain tissue.  NSF CBET EEC Grant, Chicago Science Teacher Research (CSTR) Program Director, A. Linninger  Members of LPPD, Andreas Linninger, Eric Lueshen, Sukhi Basati, Indu Venugopal, Joe Kanikunnel,Bhargav Desai  RET Fellows at UIC Control for capillary infusion 35 lb pull force magnet trial 173 lb pull force magnet trial Magnetic force was below the injection site and syringe needles were place ¼ inch above magnet in each trial. Red line indicates syringe placement. There is a general attraction of magnetic nanoparticles through the agarose toward the magnets. Superparamagnetic relaxation Spin glass arrangement Dipole alignment in the presence of a magnet Superparamagnetic Properties Biocompatible Iron ions metabolize and are biodegradable in vivo Functionalization Nanoparticles can be coated with various agents Nanoscale