PURPOSE: To present the pathologic and pharmacokinetic findings from hepatic embolization in a porcine model comparing doxorubicin-eluting beads with bland embolization and to correlate these findings with in vitro release kinetics. MATERIALS AND METHODS: Drug-eluting beads (DEB; 100-300 microm and 700-900 microm) loaded with 37.5 mg doxorubicin per milliliter hydrated beads were used to embolize the hepatic artery feeding the left lobe of the liver in young adult Yucatan pigs (n = 5 per group). Control animals underwent embolization with bland beads (100-300 microm; n = 5). Systemic plasma levels of doxorubicin were measured and correlated to in vitro drug release. Blood sampling and histopathologic examination were performed during the 90-day follow-up. RESULTS: All animals underwent successful embolization, and the treatment was well tolerated. Mean volumes of beads administered were 2.0-3.4 mL, with mean doses of 127.5 mg and 78.7 mg of doxorubicin for the 100- to 300-microm and 700- to 900-microm DEB groups, respectively. Gross pathologic examination revealed no effects on organs other than the liver. There was a transient increase in liver enzyme levels, particularly in the groups of animals who underwent embolization with 100- to 300-microm DEB. Histopathologic study showed mostly nonnecrotic changes with bland beads, whereas the effects of DEB were more severe, with large areas of pannecrosis evident with the 100- to 300-microm DEB. Maximum plasma concentrations were 651 ng/mL and 42.8 ng/mL for the 100- to 300-microm and 700- to 900-microm DEB groups, respectively, observed at 1 minute for both groups. Correlation with in vitro data showed a strong linear relationship. CONCLUSIONS: Hepatic arterial embolization with DEB was shown to be safe and well tolerated. The locoregional delivery of doxorubicin from DEB caused targeted tissue damage with minimal systemic impact and could be a promising new approach to transarterial chemoembolization of solid tumors.
PURPOSE: To present the pathologic and pharmacokinetic findings from hepatic embolization in a porcine model comparing doxorubicin-eluting beads with bland embolization and to correlate these findings with in vitro release kinetics. MATERIALS AND METHODS: Drug-eluting beads (DEB; 100-300 microm and 700-900 microm) loaded with 37.5 mg doxorubicin per milliliter hydrated beads were used to embolize the hepatic artery feeding the left lobe of the liver in young adult Yucatan pigs (n = 5 per group). Control animals underwent embolization with bland beads (100-300 microm; n = 5). Systemic plasma levels of doxorubicin were measured and correlated to in vitro drug release. Blood sampling and histopathologic examination were performed during the 90-day follow-up. RESULTS: All animals underwent successful embolization, and the treatment was well tolerated. Mean volumes of beads administered were 2.0-3.4 mL, with mean doses of 127.5 mg and 78.7 mg of doxorubicin for the 100- to 300-microm and 700- to 900-microm DEB groups, respectively. Gross pathologic examination revealed no effects on organs other than the liver. There was a transient increase in liver enzyme levels, particularly in the groups of animals who underwent embolization with 100- to 300-microm DEB. Histopathologic study showed mostly nonnecrotic changes with bland beads, whereas the effects of DEB were more severe, with large areas of pannecrosis evident with the 100- to 300-microm DEB. Maximum plasma concentrations were 651 ng/mL and 42.8 ng/mL for the 100- to 300-microm and 700- to 900-microm DEB groups, respectively, observed at 1 minute for both groups. Correlation with in vitro data showed a strong linear relationship. CONCLUSIONS: Hepatic arterial embolization with DEB was shown to be safe and well tolerated. The locoregional delivery of doxorubicin from DEB caused targeted tissue damage with minimal systemic impact and could be a promising new approach to transarterial chemoembolization of solid tumors.
Authors: Jingjie Hu; Hassan Albadawi; Brian W Chong; Amy R Deipolyi; Rahul A Sheth; Ali Khademhosseini; Rahmi Oklu Journal: Adv Mater Date: 2019-06-06 Impact factor: 30.849
Authors: Andrew L Lewis; Sean L Willis; Matthew R Dreher; Yiqing Tang; Koorosh Ashrafi; Bradford J Wood; Elliot B Levy; Karun V Sharma; Ayele H Negussie; Andrew S Mikhail Journal: Future Oncol Date: 2018-06-26 Impact factor: 3.404
Authors: Johannes Lammer; Katarina Malagari; Thomas Vogl; Frank Pilleul; Alban Denys; Anthony Watkinson; Michael Pitton; Geraldine Sergent; Thomas Pfammatter; Sylvain Terraz; Yves Benhamou; Yves Avajon; Thomas Gruenberger; Maria Pomoni; Herbert Langenberger; Marcus Schuchmann; Jerome Dumortier; Christian Mueller; Patrick Chevallier; Riccardo Lencioni Journal: Cardiovasc Intervent Radiol Date: 2009-11-12 Impact factor: 2.740