BME.13 – Regulating Nanoparticle Movement through an In-Vitro Model of the Subarachnoid Space

• Becca Ballo
• Xitlali Djangi
• Aimee Padilla
• Janvi Patel
• Mansi Peesapati

Leukemia, amongst other metastatic cancers, has been an imminent concern in the US as relapses are very common, survival rates remain low at 20%, and over 60,000 cases are diagnosed annually. Relapse and morbidity are seen due to current intrathecal injections lacking therapeutic effect; drugs are unable to diffuse ubiquitously through the spine, against CSF flow, to tackle the cancer before metastasis. Rotating magnetic nanoparticles (rMNPs) show promise as vehicles for drug delivery, as they can be controlled externally (via magnetic field) and show great surface-walking abilities across large distances. We aim to develop a physiologically accurate spinal model through which to perfuse CSF and test how rMNPs travel against resistive CSF flow. The most important design requirements include transparency of the model for visualization of rMNPs, continuous CSF flow at varying flow rates between 10-50 mL/min, and a resin scaffold for future cell culture. We use two models to test: an 8-lane culture plate which provides potential for rMNP movement in a cellular environment, and a biomimetic model of the subarachnoid space to ensure the travel of rMNPs across the full spinal distance. Using the cross-sectional area of the plate lane and the velocity of a tracking dye across the lane, we verify that CSF flow rates are optimal. Material is verified visually for transparency. rMNP flow is quantified by timing their movement across a known distance and calculating for particle velocity. It was observed that rMNPs aggregated and successfully moved against opposing CSF flow between 10-50 mL/min, and could be stopped as needed. An inverse relationship between rMNP velocity and CSF flow rate was found. With this model, we hope to further understand the behavior of rMNP against various resistive forces (cells, gels, etc.) and test their capabilities with drug loading and delivery through CSF pathways.