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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 398-406 |
| Number of pages | 9 |
| Journal | Journal of Biomedical Materials Research - Part A |
| Volume | 69 |
| Issue number | 3 |
| State | Published - Jun 1 2004 |
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Keywords
- Doxorubicin transport
- Intratumoral drug delivery
- Polymer implants
- Radiofrequency ablation
- Wound-healing response
ASJC Scopus subject areas
- Biomedical Engineering
- Biomaterials
Cite this
Effect of fibrous capsule formation on doxorubicin distribution in radiofrequency ablated rat livers. / Blanco, Elvin; Qian, Feng; Weinberg, Brent; Stowe, Nicholas; Anderson, James M.; Gao, Jinming.
In: Journal of Biomedical Materials Research - Part A, Vol. 69, No. 3, 01.06.2004, p. 398-406.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effect of fibrous capsule formation on doxorubicin distribution in radiofrequency ablated rat livers
AU - Blanco, Elvin
AU - Qian, Feng
AU - Weinberg, Brent
AU - Stowe, Nicholas
AU - Anderson, James M.
AU - Gao, Jinming
PY - 2004/6/1
Y1 - 2004/6/1
N2 - 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.
AB - 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.
KW - Doxorubicin transport
KW - Intratumoral drug delivery
KW - Polymer implants
KW - Radiofrequency ablation
KW - Wound-healing response
UR - http://www.scopus.com/inward/record.url?scp=2442711481&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=2442711481&partnerID=8YFLogxK
M3 - Article
C2 - 15127386
AN - SCOPUS:2442711481
VL - 69
SP - 398
EP - 406
JO - Journal of Biomedical Materials Research - Part A
JF - Journal of Biomedical Materials Research - Part A
SN - 0021-9304
IS - 3
ER -