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Numerical Modeling of High-Intensity Focused Ultrasound-Mediated Intraperitoneal Delivery of Thermosensitive Liposomal Doxorubicin for Cancer Chemotherapy Publisher Pubmed



Rezaeian M1 ; Sedaghatkish A2 ; Soltani M1, 3, 4, 5, 6
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 Mechanical Engineering, Isfahan University of Technology, Isfahan, Iran
  3. 3. Advanced Bioengineering Initiative Center, Computational Medicine Center, K. N. Toosi University of Technology, Tehran, Iran
  4. 4. Department of Electrical and Computer Engineering, University of Waterloo, Waterloo, Canada
  5. 5. Centre for Biotechnology and Bioengineering (CBB), University of Waterloo, Waterloo, Canada
  6. 6. Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran

Source: Drug Delivery Published:2019


Abstract

Although intraperitoneal chemotherapy (IPC) has been suggested as a promising method for the management of peritoneal dissemination (PD) of ovarian or colorectal cancers, the actual clinical use of this method has been restricted due to such problems as poor drug penetration into the tumor and high side effects. It is, therefore, necessary to develop new strategies to improve the efficacy of this approach. In the present work, a new strategy is proposed based on intraperitoneal (IP) injection of thermosensitive liposomal doxorubicin (TSL-Dox) with triggered release by mild hyperthermia induced by high intensity focused ultrasound (HIFU). A computational model is developed to evaluate the proposed drug delivery system. Results show an order of magnitude increase in drug penetration depth into the tumor compared to the conventional IP delivery. Furthermore, the effects of thermal conditions applied to the tumor, TSL size, tumor vessel permeability, and tumor size are investigated. Results indicate an improved efficiency of the drug delivery by expanding the heated region, yet, it increases the risk of unintentional TSL drug load release in the peritoneal cavity. Results also indicate that smaller TSLs have better treatment outcome. However, there is a significant reduction in treatment efficacy for TSLs with sizes smaller than the vessel wall pore size. Thus, tuning the size of TSL should be based on the tumor microvascular permeability. The simulation results suggest that the TSL-Dox delivery system in smaller tumors is far advantageous than larger ones. Results of our model can be used as guidelines for future preclinical studies. © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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