title: 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.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Elvin
authors.initials: E
authors.lastname: Blanco
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
authors.forename: Brent
authors.initials: B
authors.lastname: Weinberg
authors.forename: Nicholas
authors.initials: N
authors.lastname: Stowe
authors.forename: James M
authors.initials: JM
authors.lastname: Anderson
authors.forename: Jinming
authors.initials: J
authors.lastname: Gao
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004343:Drug Implants; D004564:Electrocoagulation; D005355:Fibrosis; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008433:Mathematics; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing
chemical_list: D000903:Antibiotics, Antineoplastic; D004343:Drug Implants; D004317:Doxorubicin