MagneticallyGuided Nanoparticle Drug Delivery Seth Baker RET Fellow

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 Introduction Magnetite Nanoparticles Superparamagnetic Properties Motivation • Direct application for improved medical treatments of neurological disorders Biocompatible cerebral artery - 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 Superparamagnetic relaxation - Targeted delivery can lower dosage and reduce cytotoxicity Spin glass arrangement Nanoscale Functionalization Objective Many therapeutic drugs for treatment of neurological conditions can cause systemic toxicity due to limited targeting of effected tissue. Magneticallyguided 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. Iron ions metabolize and are biodegradable in vivo Dipole alignment in the presence of a magnet Nanoparticles can be coated with various agents Experimental Design Convection Enhanced Delivery Step Catheters Capillary Experiments 0. 26 mm diameter step catheter tip Capillary experiment set 35 and 173 pound pull force up with 1. 0 ml syringe force magnets affect on magnet under capillary and 30 nm magnetite infused agarose gel capillary experiment Rat Brain Tests New Era Pump System syringe pump 6. 0% Agarose gel Polyethylene tubing (various gauges) Prussian Blue Stain Polymer step catheters (various gauges) Plastic cell blocks 1. 0 ml medical syringes Surfactants Magnetic nanoparticles (various diameters) Glass slides for slicing gel Sodium Hydroxide Canon EOS Rebel Xti Magnets of various pull force Rat brain tissue Coronal slices of rat brain after placed in Prussian blue dye to determine untreated brain susceptibility to staining. Testing Magnetic Susceptibility Results Magnetic force was below the injection site and syringe needles were place ¼ inch above magnet in each trial. Red line indicates syringe placement. 30 nanometer Magnetite particles above a 173 pound pull force magnet at 0 minutes 30 nanometer Magnetite particles above a 173 pound pull force magnet at 4 minutes Conclusion • 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. 30 nanometer Magnetite particles above a 173 pound pull force magnet at 8 minutes Coronal slices of rat brain showing distribution profile of Prussia blue dye. 30 nm magnetite particles delivered on rat brain tissue to determine susceptibility to nanoparticles. Control for capillary infusion There is a general attraction of magnetic nanoparticles through the agarose toward the magnets. 173 lb pull force magnet trial Acknowledgements Future Studies 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 nanoparticles into fresh brain tissue. 35 lb pull force magnet trial NSF CBET EEC-0743068 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