Magnetically-Guided Nanoparticle Drug Delivery Seth Baker, RET Fellow 2011Percy 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.

0.26 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

6.0% 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 nanoparticlesStudying 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 infusionImprove methods of introducing magnetic nanoparticles into fresh brain tissue.

NSF CBET EEC-0743068 Grant, Chicago Science Teacher Research (CSTR) Program Director, A. LinningerMembers of LPPD, Andreas Linninger, Eric Lueshen, Sukhi Basati, Indu Venugopal, Joe Kanikunnel ,Bhargav DesaiRET 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