Abstract
In this study, we report the histological findings of a combined therapy using radiofrequency ablation and intratumoral drug delivery in rat livers, with special attention to wound‐healing processes and their effects on drug transport in post‐ablated tissue. Doxorubicin‐loaded millirods were implanted in rat livers that had undergone medial lobe ablation. Millirods and liver samples were retrieved upon animal sacrifice at time points ranging from 1 h to 8 days. Results demonstrate a clearly defined area of coagulative necrosis within the ablation boundary. The wound‐healing response, complete with the appearance of inflammatory cells, neovascularization, and the formation of a fibrous capsule, was also observed. At the 8‐day time point, fluorescence imaging analysis showed a higher concentration of doxorubicin localized within the ablation region, with its distribution hampered primarily by fibrous capsule formation at the boundary. Given the variant nature of ablated liver, a mathematical model devised previously by our laboratory describes the data well up to 4 days, but loses reliability at 8 days. These results provide useful mechanistic insights into the wound‐healing response after radiofrequency ablation and polymer millirod implantation, as well as the impact this natural corollary has on drug distribution. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 398–406, 2004