Systemic administration of drugs in tumors is a challenging task due to unorganized microvasculature and nonuniform extravasation. There is an imperative need to understand the transport behavior 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 2–20 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.
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Research-Article
Numerical Study of Transport of Anticancer Drugs in Heterogeneous Vasculature of Human Brain Tumors Using Dynamic Contrast Enhanced-Magnetic Resonance Imaging
Ajay Bhandari,
Ajay Bhandari
Department of Mechanical Engineering,
Indian Institute of Technology,
Kanpur 208016, India
e-mail: ajayb@iitk.ac.in
Indian Institute of Technology,
Kanpur 208016, India
e-mail: ajayb@iitk.ac.in
Search for other works by this author on:
Ankit Bansal,
Ankit Bansal
Department of Mechanical and
Industrial Engineering,
Indian Institute of Technology,
Roorkee 247677, India
e-mail: abansfme@iitr.ac.in
Industrial Engineering,
Indian Institute of Technology,
Roorkee 247677, India
e-mail: abansfme@iitr.ac.in
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Anup Singh,
Anup Singh
Centre for Biomedical Engineering,
Indian Institute of Technology,
Delhi 110016, India;
Indian Institute of Technology,
Delhi 110016, India;
Department of Biomedical Engineering,
All India Institute of Medical Sciences,
Delhi 110016, India
e-mail: anupsm@cbme.iitd.ac.in
All India Institute of Medical Sciences,
Delhi 110016, India
e-mail: anupsm@cbme.iitd.ac.in
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Niraj Sinha
Niraj Sinha
Department of Mechanical Engineering,
Indian Institute of Technology,
Kanpur 208016, India
e-mail: nsinha@iitk.ac.in
Indian Institute of Technology,
Kanpur 208016, India
e-mail: nsinha@iitk.ac.in
Search for other works by this author on:
Ajay Bhandari
Department of Mechanical Engineering,
Indian Institute of Technology,
Kanpur 208016, India
e-mail: ajayb@iitk.ac.in
Indian Institute of Technology,
Kanpur 208016, India
e-mail: ajayb@iitk.ac.in
Ankit Bansal
Department of Mechanical and
Industrial Engineering,
Indian Institute of Technology,
Roorkee 247677, India
e-mail: abansfme@iitr.ac.in
Industrial Engineering,
Indian Institute of Technology,
Roorkee 247677, India
e-mail: abansfme@iitr.ac.in
Anup Singh
Centre for Biomedical Engineering,
Indian Institute of Technology,
Delhi 110016, India;
Indian Institute of Technology,
Delhi 110016, India;
Department of Biomedical Engineering,
All India Institute of Medical Sciences,
Delhi 110016, India
e-mail: anupsm@cbme.iitd.ac.in
All India Institute of Medical Sciences,
Delhi 110016, India
e-mail: anupsm@cbme.iitd.ac.in
Niraj Sinha
Department of Mechanical Engineering,
Indian Institute of Technology,
Kanpur 208016, India
e-mail: nsinha@iitk.ac.in
Indian Institute of Technology,
Kanpur 208016, India
e-mail: nsinha@iitk.ac.in
1Corresponding author.
Manuscript received August 15, 2017; final manuscript received November 7, 2017; published online March 16, 2018. Assoc. Editor: Ram Devireddy.
J Biomech Eng. May 2018, 140(5): 051010 (10 pages)
Published Online: March 16, 2018
Article history
Received:
August 15, 2017
Revised:
November 7, 2017
Citation
Bhandari, A., Bansal, A., Singh, A., and Sinha, N. (March 16, 2018). "Numerical Study of Transport of Anticancer Drugs in Heterogeneous Vasculature of Human Brain Tumors Using Dynamic Contrast Enhanced-Magnetic Resonance Imaging." ASME. J Biomech Eng. May 2018; 140(5): 051010. https://doi.org/10.1115/1.4038746
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