Magnetically-Guided Nanoparticle Drug Delivery Seth Baker, RET Fellow 2011 Percy Julian Middle...
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Transcript of Magnetically-Guided Nanoparticle Drug Delivery Seth Baker, RET Fellow 2011 Percy Julian Middle...
Magnetically-Guided Nanoparticle Drug Delivery Seth Baker, RET Fellow 2011
Percy Julian Middle SchoolRET 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
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-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
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