BACKGROUND: In the fight against cancer, new drug delivery systems are attractive to improve drug targeting of tumors, maximize drug potency, and minimize systemic toxicity. We studied a new drug delivery system comprising microspheres, with unique properties allowing delivery of large amounts of drugs to tumors for a prolonged time, thereby decreasing plasma levels. Liver tumors, unlike nontumorous liver, draw most of their blood supply from the hepatic artery. Exploiting this property, we delivered drug-eluting microspheres/beads (DEB) loaded with doxorubicin, intra-arterially, in an animal model of liver cancer (Vx-2). PURPOSE: The purpose of our study was to determine the pharmacokinetics and tumor-killing efficacy of DEB. RESULTS: Our results show that plasma concentration of doxorubicin was minimal in the animals treated with DEB at all time points (0.009-0.05 micromol/L), suggesting high tumor retention of doxorubicin. This was significantly lower (70-85% decrease in plasma concentration) than control animals treated with doxorubicin intra-arterially. Within the tumor, doxorubicin concentration peaked at 3 days (413.5 nmol/g), remaining high to 7 days (116.7 nmol/g) before declining at 14 days (41.76 nmol/g), indicating continuous doxorubicin elution from beads. In control animals, peak tumor concentration of doxorubicin was 0.09 nmol/g. Tumor necrosis (approaching 100%) was greatest at 7 days, with minimal adverse local side effects reflected in liver function tests results. The plasma concentration of doxorubicinol (doxorubicin main metabolite) was minimal. CONCLUSIONS: Our results support the concept of DEBs as an effective way to deliver drugs to tumor. This new technology may prove to be a useful weapon against liver cancer.
BACKGROUND: In the fight against cancer, new drug delivery systems are attractive to improve drug targeting of tumors, maximize drug potency, and minimize systemic toxicity. We studied a new drug delivery system comprising microspheres, with unique properties allowing delivery of large amounts of drugs to tumors for a prolonged time, thereby decreasing plasma levels. Liver tumors, unlike nontumorous liver, draw most of their blood supply from the hepatic artery. Exploiting this property, we delivered drug-eluting microspheres/beads (DEB) loaded with doxorubicin, intra-arterially, in an animal model of liver cancer (Vx-2). PURPOSE: The purpose of our study was to determine the pharmacokinetics and tumor-killing efficacy of DEB. RESULTS: Our results show that plasma concentration of doxorubicin was minimal in the animals treated with DEB at all time points (0.009-0.05 micromol/L), suggesting high tumor retention of doxorubicin. This was significantly lower (70-85% decrease in plasma concentration) than control animals treated with doxorubicin intra-arterially. Within the tumor, doxorubicin concentration peaked at 3 days (413.5 nmol/g), remaining high to 7 days (116.7 nmol/g) before declining at 14 days (41.76 nmol/g), indicating continuous doxorubicin elution from beads. In control animals, peak tumor concentration of doxorubicin was 0.09 nmol/g. Tumor necrosis (approaching 100%) was greatest at 7 days, with minimal adverse local side effects reflected in liver function tests results. The plasma concentration of doxorubicinol (doxorubicin main metabolite) was minimal. CONCLUSIONS: Our results support the concept of DEBs as an effective way to deliver drugs to tumor. This new technology may prove to be a useful weapon against liver cancer.
Authors: Markus Peck-Radosavljevic; Wolfgang Sieghart; Claus Kölblinger; Markus Reiter; Martin Schindl; Gregor Ulbrich; Rudolf Steininger; Christian Müller; Rudolf Stauber; Maximilian Schöniger-Hekele; Manfred Gschwendtner; Christina Plank; Martin Funovics; Ivo Graziadei; Johannes Lammer; Thomas Gruenberger; Günther Gastl; Franz Karnel Journal: Wien Klin Wochenschr Date: 2011-09-22 Impact factor: 1.704
Authors: Diane K Reyes; Josephina A Vossen; Ihab R Kamel; Nilofer S Azad; Tamara A Wahlin; Michael S Torbenson; Michael A Choti; Jean-Francois H Geschwind Journal: Cancer J Date: 2009 Nov-Dec Impact factor: 3.360