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Drug Delivery to Solid Tumors With Heterogeneous Microvascular Networks: Novel Insights From Image-Based Numerical Modeling Publisher Pubmed



Moradi Kashkooli F1, 2 ; Soltani M1, 3, 4, 5, 6 ; Hamedi MH1
Authors
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Authors Affiliations
  1. 1. Department of Mechanical Engineering, K. N. Toosi University of Technology, Tehran, Iran
  2. 2. Department of Applied Mathematics, University of Waterloo, Waterloo, ON, Canada
  3. 3. Department of Electrical and Computer Engineering, University of Waterloo, Waterloo, ON, Canada
  4. 4. Centre for Biotechnology and Bioengineering (CBB), University of Waterloo, Waterloo, ON, Canada
  5. 5. Advanced Bioengineering Initiative Center, Computational Medicine Center, K. N. Toosi University of Technology, Tehran, Iran
  6. 6. Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran

Source: European Journal of Pharmaceutical Sciences Published:2020


Abstract

The present study examines chemotherapy by incorporating multi-scale mathematical modeling to predict drug delivery and its effects. This approach leads to a more-realistic physiological tumor model than is possible with previous approaches, as it obtains the capillary network geometry from an image, and also considers the tumor's necrotic core, drug binding, and cellular uptake. Modeling of the fluid flow and drug transport is then performed in the extracellular matrix. The results demonstrate a 10% drop in the fraction of killed cancer cells [sbnd]69% rather than the 79% reported earlier for a tumor of similar geometry[sbnd] a more-accurate value. This study examines how tumor-related parameters including the necrotic core size and tumor size, and also drug-related parameters [sbnd]drug dosage, binding affinity of drug, and drug degradation[sbnd] can affect the delivery of the drug to solid tumors. Results indicate that concentration of drug are high in the tumor, low in normal tissue, and remarkably low in the necrotic core. Results also offer a treatment of tumors with smaller necrotic core. Tumor size, which implies the tumor progression, has a considerable impact on treatment outcomes, so to be more effective, treatment should be applied at a specific size of tumor. It is demonstrated that binding affinity of drugs to cell-surface receptors and drug dosage have significant impact on treatment efficacy, so they should be regulated based on a balanced quantification between maximum treatment efficacy and minimum side effects. On the other hand, considering the effects of drug degradation in the model has not significant effect on treatment efficacy. The findings of the present study provide insight into the mechanism of drug delivery to solid tumors based on analyzing the effective parameters and modeling how their behavior in the tumor microenvironment affects treatment efficacy. © 2020 Elsevier B.V.
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