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Article

Numerical Investigation on the Anti-Angiogenic Therapy-Induced Normalization in Solid Tumors

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Department of Mechanical Engineering, K. N. Toosi University of Technology, Tehran 19967-15433, Iran
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Department of Applied Mathematics, University of Waterloo, Waterloo, ON N2L 3G1, Canada
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Department of Electrical and Computer Engineering, University of Waterloo, Waterloo, ON N2L 3G1, Canada
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Advanced Bioengineering Initiative Center, Multidisciplinary International Complex, K. N. Toosi University of Technology, Tehran 14176-14411, Iran
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Centre for Biotechnology and Bioengineering (CBB), University of Waterloo, Waterloo, ON N2L 3G1, Canada
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Data Science and Artificial Intelligence Program, College of Information Sciences and Technology (IST), Penn State University, State College, PA 16801, USA
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School of Optometry and Vision Science, Faculty of Science, University of Waterloo, 200 University Ave W, Waterloo, ON N2L 3G1, Canada
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Department of Chemical Engineering, University of Waterloo, 200 University Avenue W, Waterloo, ON N2L 3G1, Canada
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Author to whom correspondence should be addressed.
Academic Editor: Timo L. M. Ten-Hagen
Pharmaceutics 2022, 14(2), 363; https://doi.org/10.3390/pharmaceutics14020363
Received: 12 December 2021 / Revised: 29 January 2022 / Accepted: 31 January 2022 / Published: 5 February 2022
(This article belongs to the Section Drug Delivery and Controlled Release)
This study numerically analyzes the fluid flow and solute transport in a solid tumor to comprehensively examine the consequence of normalization induced by anti-angiogenic therapy on drug delivery. The current study leads to a more accurate model in comparison to previous research, as it incorporates a non-homogeneous real-human solid tumor including necrotic, semi-necrotic, and well-vascularized regions. Additionally, the model considers the effects of concurrently chemotherapeutic agents (three macromolecules of IgG, F(ab)2, and F(ab)) and different normalization intensities in various tumor sizes. Examining the long-term influence of normalization on the quality of drug uptake by necrotic area is another contribution of the present study. Results show that normalization decreases the interstitial fluid pressure (IFP) and spreads the pressure gradient and non-zero interstitial fluid velocity (IFV) into inner areas. Subsequently, wash-out of the drug from the tumor periphery is decreased. It is also demonstrated that normalization can improve the distribution of solute concentration in the interstitium. The efficiency of normalization is introduced as a function of the time course of perfusion, which depends on the tumor size, drug type, as well as normalization intensity, and consequently on the dominant mechanism of drug delivery. It is suggested to accompany anti-angiogenic therapy by F(ab) in large tumor size (Req=2.79cm) to improve reservoir behavior benefit from normalization. However, IgG is proposed as the better option in the small tumor (Req=0.46cm), in which normalization finds the opportunity of enhancing uniformity of IgG average exposure by 22%. This study could provide a perspective for preclinical and clinical trials on how to take advantage of normalization, as an adjuvant treatment, in improving drug delivery into a non-homogeneous solid tumor. View Full-Text
Keywords: normalization; anti-angiogenic therapy; non-homogeneous solid tumor; necrotic area; reservoir behavior normalization; anti-angiogenic therapy; non-homogeneous solid tumor; necrotic area; reservoir behavior
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MDPI and ACS Style

Mohammadi, M.; Aghanajafi, C.; Soltani, M.; Raahemifar, K. Numerical Investigation on the Anti-Angiogenic Therapy-Induced Normalization in Solid Tumors. Pharmaceutics 2022, 14, 363. https://doi.org/10.3390/pharmaceutics14020363

AMA Style

Mohammadi M, Aghanajafi C, Soltani M, Raahemifar K. Numerical Investigation on the Anti-Angiogenic Therapy-Induced Normalization in Solid Tumors. Pharmaceutics. 2022; 14(2):363. https://doi.org/10.3390/pharmaceutics14020363

Chicago/Turabian Style

Mohammadi, Mahya, Cyrus Aghanajafi, M. Soltani, and Kaamran Raahemifar. 2022. "Numerical Investigation on the Anti-Angiogenic Therapy-Induced Normalization in Solid Tumors" Pharmaceutics 14, no. 2: 363. https://doi.org/10.3390/pharmaceutics14020363

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