Effect of fibrous capsule formation on doxorubicin distribution in radiofrequency ablated rat livers.

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.