Modeling doxorubicin transport to improve intratumoral drug delivery to RF ablated tumors

Brent D. Weinberg, Ravi B. Patel, Agata A. Exner, Gerald M. Saidel, Jinming Gao

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)11-19
Number of pages9
JournalJournal of Controlled Release
Volume124
Issue number1-2
DOIs
StatePublished - Dec 4 2007

Keywords

  • Biodegradable implant
  • Local chemotherapy
  • Mathematical modeling
  • Radiofrequency ablation
  • VX2 tumor

ASJC Scopus subject areas

  • Pharmaceutical Science

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