Quantification of in vivo doxorubicin transport from PLGA millirods in thermoablated rat livers

The objective of this research was to quantify the key parameters governing the drug transport processes in radiofrequency (RF) thermoablated and non-ablated liver tissues. Experimentally, doxorubicin-containing polymer millirods were implanted in the ablated rat livers and spatial distribution of doxorubicin was measured by fluorescence imaging from 1 to 96 h after millirod implantation. At all time points, doxorubicin had significantly higher tissue penetration and retention in ablated tissues than in non-ablated tissues. A mathematical model was developed to quantitatively describe the transport processes in ablated and non-ablated rat livers. Based on the experimental data and mathematical models, the optimal estimates of apparent drug diffusivities in ablated and non-ablated tissues were 1.1 X 10(-7) and 6.7 X 10(-7) cm(2) s(-1), respectively, and the apparent drug elimination rate coefficient was 9.6 X 10(-4) s(-1) in non-ablated tissues. Results from this study contribute to the fundamental understanding of in vivo drug transport in liver tissues and provide the quantitative parameters for the rational design of polymer millirods for liver cancer treatment. (C) 2003 Elsevier B.V. All rights reserved.