Blood flow through a leaky vasculature and its effect on drug delivery and nanoparticle transport

Interdisciplinary Areas: Engineering and Healthcare/Medicine/Biology, Micro-, Nano-, and Quantum Engineering

Project Description

There has been increasing interest in using nanoparticles to image, diagnose, and treat cancer. The scientific premise behind this idea is the enhanced permeability and retention effect (EPR) – i.e. the situation where the tumor vasulature has large (i.e., >100 nm) pores with poor lymphatic drainage, which allow 20-100 nm nanoparticles to preferentially accumulate into these regions. Although there have been impressive strides in using EPR for targeted drug delivery, it is estimated that only ~0.7% of injected nanoparticles accumulate in the tumor, while the remainder circulate in the blood until they lose bioavailability. This issue increases drug cost and decreases drug effectiveness. Therefore, there has been a push to quantify nanoparticle transport mechanisms in the tumor vasculature in order improve drug retention. 

The specific aim of this project is to simulate red blood cell suspensions moving through leaky vessels and characterize the critical leakage rates that dramatically alter the suspension’s microstructure over time. The suspension’s velocity fluctuations will be used to calculate the enhanced hydrodynamic diffusivity that nanoparticles of various sizes and shapes would experience. These simulations will shed insight as to how channel size, red blood cell concentration, leakage flux, and nanoparticle morphology alter drug delivery.

Start Date

April 2020

Postdoc Qualifications 

The postdoctoral researcher should have a degree in Chemical Engineering, Mechanical Engineering, Materials Science, or equivalent. The research requires a strong background in fluid mechanics, rheology, and computational methods.

Co-advisors 

Vivek Narsimhan
vnarsim@purdue.edu
Assistant Professor of Chemical Engineering
https://engineering.purdue.edu/ChE/people/ptProfile?resource_id=169352 

Ivan Christov
christov@purdue.edu
Assistant Professor of Mechanical Engineering
https://engineering.purdue.edu/ME/People/ptProfile?resource_id=134738

References 

V. Narsimhan, H. Zhao, and E.S.G. Shaqfeh, “Coarse-grained theory to predict the concentration distribution of red blood cells in wall-bounded Couette flow," Phys. Fluids., 25, 061901, (2013). DOI: 10.1063/1.4810808 

H. Zhao, E.S.G. Shaqfeh, and V. Narsimhan, “Shear-induced particle migration and margination in a cellular suspension," Phys. Fluids, 24, 011902 (2012). DOI: 10.1063/1.3677935 

P. Shah, S. Fitzgibbon, V. Narsimhan, and E.S.G. Shaqfeh. “Singular perturbation theory for predicting the extravasation of Brownian particles,” J. Engng. Math, 84, 155-171, (2014). DOI: 10.1007/s10665-013-9665-2 

F. Municchi, P. P. Nagrani and I. C. Christov, “A two-fluid model for numerical simulation of shear-dominated suspension flows,’’ Int. J. Multiphase Flow, 120, 103079 (2019). 

V. Anand, Joshua David JR and I. C. Christov, “Non-Newtonian fluid–structure interactions: Static response of a microchannel due to internal flow of a power-law fluid,” J. Non-Newtonian Fluid Mech., 264, 62–72 (2019). DOI:10.1016/j.jnnfm.2018.12.008DOI:10.1016/j.ijmultiphaseflow.2019.07.015