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Novel Drug Delivery in Pediatric Medulloblastoma

Novel Drug Delivery in Pediatric Medulloblastoma. Group 37 – Chris Peng (Presenter), Arvin Soepriatna , Blessan Seb astian Client: Mr. Mike Sabo, Pulse Therapeutics, Inc. BME 401, Prof. Anastasio 10/2/2013. Background.

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Novel Drug Delivery in Pediatric Medulloblastoma

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  1. Novel Drug Delivery in Pediatric Medulloblastoma Group 37 – Chris Peng (Presenter), Arvin Soepriatna, Blessan Sebastian Client: Mr. Mike Sabo, Pulse Therapeutics, Inc. BME 401, Prof. Anastasio 10/2/2013

  2. Background • Brain and CNS tumor:198.9/million person-years between 2004 and 2008.[1] • Medulloblastoma: • Originates in the brain and unlike most brain tumors, spreads through cerebrospinal fluids • Occurrence is about 10 times higher in children under 19 than adults[1][2] • accounts for 15% of all brain tumors in age group 0-14[1] [1] “CBTRUS Statistical Report: Primary Brain and Central Nervous Tumors Diagnosed in the United States in 2004-2008.” Central Brain Tumor Registry of the US, 23 Mar. 2012 Revision. Web. Retrieved 29 Sep. 2013 <www.cbtrus.org> [2] Smoll, N.R. and Drummond, K.J. “The Incidence of Medulloblastomas and Primitive NeurectodermalTumours in Adults and Children.”, Journal of Clinical Neuroscience 19(2012), 1541-44. Print.

  3. Background • Current Drug Delivery Processes [1][2] : • Dispersed and non-specific • Minimal control • Chemotherapy side-effects in children[3]: • Low growth rate • Hypoplasia • Impaired intellectual development • Hormone deficiency and pubertal underdevelopment [1] Pankhurst, Q. A., J. Connolly, S. K. Jones, and J. Dobson. "Applications of Magnetic Nanoparticles in Biomedicine." Journal of Physics D: Applied Physics 36.13 (2003): R167-181. Print. [2] McBain, Stuart C., Yiu, Humphrey HP, and J. Dobson. "Magnetic Nanoparticles for Gene and Drug Delivery." Int. Journal of Nanomedicine 2008:3(2): 169-180. Print. [3] Schwartz, Cindy L. “Long-Term Survivors of Childhood Cancer: The Late Effects of Therapy.” The Oncologist 4 (1999): 45-54

  4. Background • Alternative chemotherapy solution: drug-conjugated magnetic nanoparticles • Proposed advantages[1]: • Target specific locations • Allows control of particles • Can be synthesized to needs • Can be manipulated to become hyperthermiaagents • Superparamagneticparticles are preferred Figure Source: [1] [1] Pankhurst, Q. A., J. Connolly, S. K. Jones, and J. Dobson. "Applications of Magnetic Nanoparticles in Biomedicine." Journal of Physics D: Applied Physics 36.13 (2003): R167-181. Print.

  5. Background • Pulse Therapeutics, Inc.: Drug delivery in stroke patients using drug infused magnetic NPs

  6. Needs • More effective chemotherapeutic drug delivery system • Ability to target specific locations • Increased drug dosage without side-effects

  7. Project Scope • Develop an improved drug delivery mechanism, which includes: • Designing a device with a rotating magnet and an imaging system; • Determining the operational parameters; • Outlining a control algorithm to transport, relocate and recollect the particles.

  8. Design Specifications

  9. Current ApproachesMagnetic NP Control • Shapiro, Lin, and Probst Group: • Localization cannot be achieved using a static field • 8-electromagnet system at45o angle with each other Source: Lin, J., Shapiro, B., and Probst, R. “Particle Steering by Active Control of Magnetic Fields, and Magnetic Particle Agglomeration Avoidance”, ISR Technical Report (2008): 22

  10. Current Approaches Magnetic NP Control Source: Benjamin Shapiro. “Towards Dynamic Control of Magnetic Fields to Focus Magnetic Carriers to Target Deep Inside the Body”, Journal of Magnetism and Magnetic Materials, 321 (2009): 1594-99. Print.

  11. Current Approaches Magnetic NP Control • Shapiro group found an equation for ferrofluid acceleration but with significant errors • Cause: assumption that the NPs travel in spherical shape – error in drag force • In reality they travel in a stream-like manner • Model does fit general trend of data – further improvement could be made Source: Lin, J., Shapiro, B., and Probst, R. “Particle Steering by Active Control of Magnetic Fields, and Magnetic Particle Agglomeration Avoidance”, ISR Technical Report (2008): 22

  12. Current Approaches Visualization and Tracking • MRI • High Resolution • Good Contrast • Requires static directional magnetic force • Traditional MRI is not applicable for real-time imaging and NP tracking

  13. Current Approaches Visualization and Tracking • Tokura Group: • Possible to control and visualize simultaneously using particle tracking velocimetry • Uses light sources to illuminate and locate the moving particles • Correlation between velocity and flux • Has not been used on biological applications Source: Tokura, S., M. Hara, et al. “Visualization of Magnetic Microparticles in Liquid and Control of Their Motion Using Dynamic Magnetic Field.” Journal of Applied Physics 107.9, (2010): 09B521. Print

  14. Challenges • Application from laboratory setting to biological setting • Non-ideal conditions • Design and spacing

  15. Preliminary Calculations • Magnetic force on NPs[1]: • Particle V=1.13 x 10-22 m3 • Fmag at 50mm distance ≈ 6 x 10-21 N • Does not account of drag force • Acceleration is on an acceptable magnitude: ~10-4 m/s2 [1] Dobson, Jon. "Magnetic Nanoparticles for Drug Delivery." Drug Development Research. 67. (2006): 55-60. Print.

  16. Project Timeline

  17. Team Organization

  18. Thank you for listening!

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