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

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 incorporate...

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Autores principales: Mohammadi, Mahya, Aghanajafi, Cyrus, Soltani, M., Raahemifar, Kaamran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8877966/
https://www.ncbi.nlm.nih.gov/pubmed/35214095
http://dx.doi.org/10.3390/pharmaceutics14020363
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author Mohammadi, Mahya
Aghanajafi, Cyrus
Soltani, M.
Raahemifar, Kaamran
author_facet Mohammadi, Mahya
Aghanajafi, Cyrus
Soltani, M.
Raahemifar, Kaamran
author_sort Mohammadi, Mahya
collection PubMed
description 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 [Formula: see text] , [Formula: see text] , and [Formula: see text]) 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 [Formula: see text] in large tumor size ([Formula: see text]) to improve reservoir behavior benefit from normalization. However, [Formula: see text] is proposed as the better option in the small tumor ([Formula: see text]), in which normalization finds the opportunity of enhancing uniformity of [Formula: see text] 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.
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spelling pubmed-88779662022-02-26 Numerical Investigation on the Anti-Angiogenic Therapy-Induced Normalization in Solid Tumors Mohammadi, Mahya Aghanajafi, Cyrus Soltani, M. Raahemifar, Kaamran Pharmaceutics Article 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 [Formula: see text] , [Formula: see text] , and [Formula: see text]) 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 [Formula: see text] in large tumor size ([Formula: see text]) to improve reservoir behavior benefit from normalization. However, [Formula: see text] is proposed as the better option in the small tumor ([Formula: see text]), in which normalization finds the opportunity of enhancing uniformity of [Formula: see text] 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. MDPI 2022-02-05 /pmc/articles/PMC8877966/ /pubmed/35214095 http://dx.doi.org/10.3390/pharmaceutics14020363 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mohammadi, Mahya
Aghanajafi, Cyrus
Soltani, M.
Raahemifar, Kaamran
Numerical Investigation on the Anti-Angiogenic Therapy-Induced Normalization in Solid Tumors
title Numerical Investigation on the Anti-Angiogenic Therapy-Induced Normalization in Solid Tumors
title_full Numerical Investigation on the Anti-Angiogenic Therapy-Induced Normalization in Solid Tumors
title_fullStr Numerical Investigation on the Anti-Angiogenic Therapy-Induced Normalization in Solid Tumors
title_full_unstemmed Numerical Investigation on the Anti-Angiogenic Therapy-Induced Normalization in Solid Tumors
title_short Numerical Investigation on the Anti-Angiogenic Therapy-Induced Normalization in Solid Tumors
title_sort numerical investigation on the anti-angiogenic therapy-induced normalization in solid tumors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8877966/
https://www.ncbi.nlm.nih.gov/pubmed/35214095
http://dx.doi.org/10.3390/pharmaceutics14020363
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