TY - JOUR
T1 - Modeling doxorubicin transport to improve intratumoral drug delivery to RF ablated tumors
AU - Weinberg, Brent D.
AU - Patel, Ravi B.
AU - Exner, Agata A.
AU - Saidel, Gerald M.
AU - Gao, Jinming
N1 - Funding Information:
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 016 from the ‘Cell Stress and Cancer Nanomedicine’ program in the Simmons Comprehensive Cancer Center at the University of Texas Southwestern Medical Center at Dallas.
PY - 2007/12/4
Y1 - 2007/12/4
N2 - A mathematical model of drug transport provides an ideal strategy to optimize intratumoral drug delivery implants to supplement radiofrequency (RF) ablation for tumor treatment. To simulate doxorubicin transport in non-ablated and ablated liver tumors, a one-dimensional, cylindrically symmetric transport model was generated using a finite element method (FEM). Parameters of this model, the diffusion (D) and elimination (γ) coefficients for doxorubicin, were estimated using drug distributions measured 4 and 8 days after placing biodegradable implants in non-ablated and ablated rabbit VX2 liver carcinomas. In non-ablated tumor, values of diffusion and elimination parameters were 25% and 94% lower than normal liver tissue, respectively. In ablated tumor, diffusion near the ablation center was 75% higher than non-ablated tumor but decreased to the non-ablated tumor value at the ablation periphery. Drug elimination in ablated tumor was zero for the first four days, but by day 8 returned to 98% of the value for non-ablated tumor. Three-dimensional (3-D) simulations of drug delivery from implants with and without RF thermal ablation underscore the benefit of using RF ablation to facilitate local drug distribution. This study demonstrates the use of computational modeling and optimal parameter estimation to predict local drug pharmacokinetics from intratumoral implants after ablation.
AB - A mathematical model of drug transport provides an ideal strategy to optimize intratumoral drug delivery implants to supplement radiofrequency (RF) ablation for tumor treatment. To simulate doxorubicin transport in non-ablated and ablated liver tumors, a one-dimensional, cylindrically symmetric transport model was generated using a finite element method (FEM). Parameters of this model, the diffusion (D) and elimination (γ) coefficients for doxorubicin, were estimated using drug distributions measured 4 and 8 days after placing biodegradable implants in non-ablated and ablated rabbit VX2 liver carcinomas. In non-ablated tumor, values of diffusion and elimination parameters were 25% and 94% lower than normal liver tissue, respectively. In ablated tumor, diffusion near the ablation center was 75% higher than non-ablated tumor but decreased to the non-ablated tumor value at the ablation periphery. Drug elimination in ablated tumor was zero for the first four days, but by day 8 returned to 98% of the value for non-ablated tumor. Three-dimensional (3-D) simulations of drug delivery from implants with and without RF thermal ablation underscore the benefit of using RF ablation to facilitate local drug distribution. This study demonstrates the use of computational modeling and optimal parameter estimation to predict local drug pharmacokinetics from intratumoral implants after ablation.
KW - Biodegradable implant
KW - Local chemotherapy
KW - Mathematical modeling
KW - Radiofrequency ablation
KW - VX2 tumor
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U2 - 10.1016/j.jconrel.2007.08.023
DO - 10.1016/j.jconrel.2007.08.023
M3 - Article
C2 - 17900740
AN - SCOPUS:36048936360
SN - 0168-3659
VL - 124
SP - 11
EP - 19
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 1-2
ER -