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

BackgroundBrain 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 fluidsOccurrence 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 Neurectodermal Tumours in Adults and Children.”, Journal of Clinical Neuroscience 19(2012), 1541-44. Print.

BackgroundCurrent Drug Delivery Processes [1][2] :

Dispersed and non-specificMinimal control

Chemotherapy side-effects in children[3]:Low growth rate HypoplasiaImpaired intellectual developmentHormone 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

BackgroundAlternative chemotherapy solution: drug-

conjugated magnetic nanoparticlesProposed advantages[1]:

Target specific locationsAllows control of particlesCan be synthesized to needsCan be manipulated to become

hyperthermia agentsSuperparamagnetic particles are preferred

[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.

Figure Source: [1]

BackgroundPulse Therapeutics, Inc.: Drug delivery in

stroke patients using drug infused magnetic NPs

NeedsMore effective chemotherapeutic drug

delivery system

Ability to target specific locations

Increased drug dosage without side-effects

Project ScopeDevelop 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.

Design SpecificationsParameters SpecificationsSize < 3x3 ftWeight ≤ 40 lbsMagnetic Field Strength < 1 TLocalization Duration < 5 minParticle Position Accuracy ±2 mmImaging Depth At least 20cmStandard Operation Time < 4 hrsSystem Power Inlet Standard 110V

Current ApproachesMagnetic NP ControlShapiro, 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

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.

Current Approaches Magnetic NP Control

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 mannerModel 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

Current Approaches Visualization and Tracking

MRI High ResolutionGood ContrastRequires static directional magnetic force

Traditional MRI is not applicable for real-time imaging and NP tracking

Current Approaches Visualization and TrackingTokura 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 fluxHas 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

ChallengesApplication from laboratory setting to

biological settingNon-ideal conditionsDesign and spacing

Preliminary CalculationsMagnetic force on NPs[1]:

Particle V=1.13 x 10-22 m3

Fmag at 50mm distance ≈ 6 x 10-21 NDoes not account of drag forceAcceleration 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.

Project Timeline

Team OrganizationTeam Member Responsibilities

Chris Peng Preliminary PresentationWebpage, Coding and Algorithms

Arvin Soepriatna Progress PresentationResearch and Experimental

AnalysisBlessan Sebastian Final Presentation

Design Parameters and Safety

Thank you for listening!