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Model simulation and experimental validation of intratumoral chemotherapy using multiple polymer implants

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Abstract

Radiofrequency ablation has emerged as a minimally invasive option for liver cancer treatment, but local tumor recurrence is common. To eliminate residual tumor cells in the ablated tumor, biodegradable polymer millirods have been designed for local drug (e.g., doxorubicin) delivery. A limitation of this method has been the extent of drug penetration into the tumor (<5 mm), especially in the peripheral tumor rim where thermal ablation is less effective. To provide drug concentration above the therapeutic level as needed throughout a large tumor, implant strategies with multiple millirods were devised using a computational model. This dynamic, 3-D mass balance model of drug distribution in tissue was used to simulate the consequences of various numbers of implants in different locations. Experimental testing of model predictions was performed in a rabbit VX2 carcinoma model. This study demonstrates the value of multiple implants to provide therapeutic drug levels in large ablated tumors.

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Acknowledgments

This work was supported by NIH grant R01 CA90696 to JG. BW and RP are supported in part by the NIH grant T32 GM07250 to the Case Western Reserve University Medical Scientist Training Program. BW is also supported by DOD predoctoral fellowship BC043453. This is manuscript CSCN P012 from the ‘Cell Stress and Cancer Nanomedicine’ program in the Simmons Comprehensive Cancer Center at the University of Texas Southwestern Medical Center at Dallas.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, 44106, USA

    Brent D. Weinberg, Ravi B. Patel, Gerald M. Saidel & Jinming Gao

  2. Department of Radiology, Case Western Reserve University, Cleveland, OH, 44106, USA

    Hanping Wu & Agata A. Exner

  3. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, 6001 Forest Park, Rm ND2.210, Dallas, TX, 75390, USA

    Brent D. Weinberg, Elvin Blanco, Carlton C. Barnett & Jinming Gao

Authors
  1. Brent D. Weinberg
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  2. Ravi B. Patel
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  3. Hanping Wu
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  4. Elvin Blanco
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  5. Carlton C. Barnett
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  6. Agata A. Exner
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  7. Gerald M. Saidel
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  8. Jinming Gao
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Correspondence to Jinming Gao.

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Weinberg, B.D., Patel, R.B., Wu, H. et al. Model simulation and experimental validation of intratumoral chemotherapy using multiple polymer implants. Med Biol Eng Comput 46, 1039–1049 (2008). https://doi.org/10.1007/s11517-008-0354-7

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  • DOI: https://doi.org/10.1007/s11517-008-0354-7

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