In vivo drug distribution dynamics in thermoablated and normal rabbit livers from biodegradable polymers

Jinming Gao, Feng Qian, Agata Szymanski-Exner, Nicholas Stowe, John Haaga

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Image-guided radiofrequency ablation combined with intratumoral drug delivery provides a novel and minimally invasive treatment of liver cancers. In this study, the in vivo transport properties of doxorubicin in thermoablated and nonablated rabbit livers were characterized and compared. Doxorubicin was released from polymer implants (millirods) to the ablated and nonablated liver tissue. At different time points, the 2D distribution profiles were quantitatively determined by a fluorescence imaging method. Analysis of the doxorubicin concentration at the ablation boundary showed that it reached a maximum of 49.8 μg/g at 24 h after implantation, which was higher than the reported cytotoxic concentration of doxorubicin (6.4 μg/g) for liver VX-2 cancer cells. This value dropped to 0.4 μg/g at 48 h after implantation due to the depletion of doxorubicin from the polymer millirod. Results also showed that the area of drug distribution was significantly larger in ablated tissue than nonablated tissue. The therapeutic penetration distance was found to be 5.2 mm in thermoablated livers, compared to 1.2 mm in nonablated livers at 24 h. This difference in drug transport properties is attributed to destruction of the vasculature network in the ablated tissue as supported by histological analysis. Consequently, drug washout by blood perfusion is hampered while drug diffusion becomes the dominant process of transport in the ablated tissue. Results from this study provide insightful information on the rational design and development of polymer millirods for intratumoral drug delivery applications.

Original languageEnglish (US)
Pages (from-to)308-314
Number of pages7
JournalJournal of Biomedical Materials Research
Volume62
Issue number2
DOIs
StatePublished - Nov 2002

Fingerprint

Biodegradable polymers
Liver
Doxorubicin
Tissue
Pharmaceutical Preparations
Polymers
Ablation
Drug delivery
Transport properties
Blood
Fluorescence
Cells
Imaging techniques

Keywords

  • In vivo drug transport
  • Intratumoral drug delivery
  • Poly(D,L-lactideco-glycolide)
  • Polymer implants
  • RF ablation

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials

Cite this

In vivo drug distribution dynamics in thermoablated and normal rabbit livers from biodegradable polymers. / Gao, Jinming; Qian, Feng; Szymanski-Exner, Agata; Stowe, Nicholas; Haaga, John.

In: Journal of Biomedical Materials Research, Vol. 62, No. 2, 11.2002, p. 308-314.

Research output: Contribution to journalArticle

Gao, Jinming ; Qian, Feng ; Szymanski-Exner, Agata ; Stowe, Nicholas ; Haaga, John. / In vivo drug distribution dynamics in thermoablated and normal rabbit livers from biodegradable polymers. In: Journal of Biomedical Materials Research. 2002 ; Vol. 62, No. 2. pp. 308-314.
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