Studying Drug Delivery to Gliomas

Yeqing Ni

PhD student

Northeastern University

Guadalupe Garcia

PhD student

Northeastern University

Dr. Cynthia Hajal

Assistant Professor

Northeastern University

Clayton Pierce

YSP Student

Gloucester High School

Xyden Procaccianti

YSP Student

Bishop Feehan High School

Presentation Overview

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Modeling Drug Delivery to Gliomas

Center for STEM Education - NEU Young Scholars Program - July 31st 2025

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Modeling Drug Delivery to Gliomas

Center for STEM Education - NEU Young Scholars Program - July 30th 2025

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Background

COMSOL Transport Simulation

In Vitro Model of Glioblastoma

Conclusion

Acknowledgments

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06-08

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Background

• Gliomas are a type of brain/spinal cord tumor
• Treatment includes surgical resection of the tumor, radiation, and chemotherapy
• The blood brain barrier is a layer of tightly locked vascular cells that regulate the transport of molecules from the blood to the brain
• Minimal drug penetration can encourage tumor resistance to the drug

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Modeling Drug Delivery to Gliomas

Center for STEM Education - NEU Young Scholars Program - July 30th 2025

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Created in https://BioRender.com

COMSOL Transport Simulation

Modeling Drug Delivery to Gliomas

Center for STEM Education - NEU Young Scholars Program - July 30th 2025

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What is COMSOL?

• COMSOL is an industry standard fluid & physics simulation software
• It uses geometry, meshes, domains, and boundary conditions to make a simulation model

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• In COMSOL the physics type used are Creeping Flow and Transport of Diluted Species (TDS)

1. COMSOL, Inc. (2025). COMSOL Logo. Retrieved from imgres

2. COMSOL, Inc. (2025). Geometry and Mesh Setup for Modeling Regions of Infinite Extent. Retrieved from imgres

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Modeling Drug Delivery to Gliomas

Center for STEM Education - NEU Young Scholars Program - July 30th 2025

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Problem Definition and Domains

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Creeping Flow Domains

• Wall: Give walls no slip condition
• Fluid properties: Fluid Viscosity / Density equal to 1 x 10^-3 Pa*s and 1000 kg/m³ respectively
• Initial value: Set vessel pressure = 0
• Inlet / Outlet: Inlet / outlet for fluid to flow through

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• The objective of our simulation is to model an microvascular network (MVN) adjacent to a tumor spheroid, incorporating Creeping Flow (SPF) and Transport of Diluted Species (TDS) physics to simulate the flow / diffusion of the therapeutic drug Gemcitabine

Transport Diluted Species Domains

• Thin diffusion barrier: Sets walls of vessel to be permeable
• Fluid: Allows for changes in permeability value
• No Flux: Set outside border to non-permeable
• Initial value C: Set concentration of all domains to zero
• Inflow / Outflow: Inlet / outlet for species to flow through

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Modeling Drug Delivery to Gliomas

Center for STEM Education - NEU Young Scholars Program - July 30th 2025

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Simulation Results

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Modeling Drug Delivery to Gliomas

Center for STEM Education - NEU Young Scholars Program - July 30th 2025

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• The maximum velocity in the vessel is in the physiological range, 10*10^-4 [m/s]
• At t=10h system is at equilibrium and the tumor has zero concentration 0-8 um from the center and 1.5-2.5*10^-5 [mol/m³] in the range 10-15 um from the core
• Slight negative error at 9 um

In Vitro Model of Glioblastoma

Modeling Drug Delivery to Gliomas

Center for STEM Education - NEU Young Scholars Program - July 30th 2025

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Experimental Methods

• Microfluidic Device
• Made using PDMS, cured, cut, and bonded to glass coverslips
• Contains 2 media channels and 1 central hydrogel/cell channel
• Cell Seeding and Treatment
• Tumor spheroids made by plating 2000 cells/well of a 96-well plate (by mentor)
• Grown for 4-7 days, then seeded in devices with different hydrogel stiffnesses (by mentor)
• Treated with TMZ or DMSO on Day 1; drug replenished daily
• Imaged over 8 days using brightfield microscopy (by mentor)
• Spheroid Quantification
• Analyzed using ImageJ for area, optical density, and diameter (by mentor)

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Modeling Drug Delivery to Gliomas

Center for STEM Education - NEU Young Scholars Program - July 30th 2025

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Created in https://BioRender.com

Experimental Results

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Modeling Drug Delivery to Gliomas

Center for STEM Education - NEU Young Scholars Program - July 30th 2025

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Experimental Results Pt 2

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Modeling Drug Delivery to Gliomas

Center for STEM Education - NEU Young Scholars Program - July 30th 2025

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Conclusion

• Tumors are generally less responsive in stiff conditions
• They will not grow as much when not treated, but also that they do not shrink as much when treated with the drug
• Tumor is more difficult to treat in stiffer conditions
• COMSOL simulation is relevant based on gathered values
• In in the future intent to grow vasculature to make lab model and simulation more closely relate & simulate more complex and realistic vasculature in COMSOL
• Future intent to simulate tumor shrinkage via COMSOL solid mechanics.
• Address negative concentration error in COMSOL

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Modeling Drug Delivery to Gliomas

Center for STEM Education - NEU Young Scholars Program - July 30th 2025

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Acknowledgements

TUMOR Lab

Dr. Cynthia Hajal, Professor of Mechanical & Industrial Engineering

Guadalupe Garcia, Mechanical Engineering Ph.D Student

Yeqing Ni, Mechanical Engineering Ph.D Student

Center for STEM Education​

Claire Duggan, Executive Director

Jennifer Love, Associate Director

Victoria Berry, D’mitra Mukasa, & Ahmed Othman, YSP Coordinators​

Nicolas Fuchs, Program Manager

Mary Howley. Administrative Officer

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Modeling Drug Delivery to Gliomas

Center for STEM Education - NEU Young Scholars Program - July 30th 2025

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References

1. Hajal, C., Offeddu, G. S., Shin, Y., Zhang, S., Morozova, O., Hickman, D., Knutson, C. G., & Kamm, R. D. (2022). Engineered human blood–brain barrier microfluidic model for vascular permeability analyses. Nature Protocols, 17(1), 95–128. https://doi.org/10.1038/s41596-021-00635-w
2. Offeddu, G. S., Haase, K., Gillrie, M. R., Li, R., Morozova, O., Hickman, D., Knutson, C. G., & Kamm, R. D. (2019). An on-chip model of protein paracellular and transcellular permeability in the microcirculation. Biomaterials, 212, 115–125. https://doi.org/10.1016/j.biomaterials.2019.05.022

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Modeling Drug Delivery to Gliomas

Center for STEM Education - NEU Young Scholars Program - July 30th 2025

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