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research-article

Numerical Study of Transport of Anti-Cancer Drugs in Heterogeneous Vasculature of Human Brain Tumors using DCE-MRI

[+] Author and Article Information
Ajay Bhandari

Department of Mechanical Engineering, Indian Institute of Technology, Kanpur-208016, India
ajayb@iitk.ac.in

Ankit Bansal

Department of Mechanical and Industrial Engineering, Indian Institute of Technology, Roorkee- 247677, India
abansfme@iitr.ac.in

Anup Singh

Centre for Biomedical Engineering, Indian Institute of Technology, Delhi- 110016, India; Department of Biomedical Engineering, All India Institute of Medical Sciences, Delhi- 110016, India
anupsm@cbme.iitd.ac.in

Niraj Sinha

Department of Mechanical Engineering, Indian Institute of Technology, Kanpur-208016, India
nsinha@iitk.ac.in

1Corresponding author.

ASME doi:10.1115/1.4038746 History: Received August 15, 2017; Revised November 07, 2017

Abstract

Systemic administration of drugs in tumors is a challenging task due to unorganized microvasculature and non-uniform extravasation. There is an imperative need to understand the transport behaviour of drugs when administered intravenously. In this study, a transport model is developed to understand the therapeutic efficacy of a free drug and liposome encapsulated drugs (LED), in heterogeneous vasculature of human brain tumors. Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) data is employed to model the heterogeneity in tumor vasculature that is directly mapped onto the computational fluid dynamics (CFD) model. Results indicate that heterogeneous vasculature leads to preferential accumulation of drugs at the tumor position. Higher drug accumulation was found at location of higher interstitial volume, thereby facilitating more tumor cell killing at those areas. Liposome released drug (LRD) remains inside the tumor for longer time as compared to free drug, which together with higher concentration enhances therapeutic efficacy. The interstitial as well as intracellular concentration of LRD is found to be 2 to 20 fold higher as compared to free drug, which are in line with experimental data reported in literature. Close agreement between the predicted and experimental data demonstrates the potential of the developed model in modeling the transport of LED and free drugs in heterogeneous vasculature of human tumors.

Copyright (c) 2017 by ASME
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