Hepatic Arterial Embolization with Doxorubicin-Loaded Superabsorbent Polymer Microspheres in a Rabbit Liver Tumor Model

Abstract

The pharmacokinetic profile after hepatic arterial embolization with superabsorbent microspheres (QuadraSpheres) loaded with doxorubicin was studied. Rabbits with hepatic VX2 tumors were treated with intra-arterial administration of QuadraSpheres loaded with doxorubicin, or transarterial chemoembolization (TACE) using doxorubicin, Lipiodol and Embospheres, or hepatic arterial infusion (HAI) of doxorubicin. Tumor specimens were evaluated by fluorescence microscopy, and plasma and tumor concentrations of doxorubicin were measured. The peak plasma concentration of doxorubicin was lower in the QuadraSphere group (309.9ng/ml) than in the HAI (673.4ng/ml) or TACE (360.5ng/ml) groups, suggesting higher tumor retention in the QuadraSphere group. Intratumoral doxorubicin levels declined to negligible levels at 1 and 3days after treatment, respectively, in the HAI and TACE groups. In the QuadraSphere groups, intratumoral doxorubicin level declined after day 1, but was still detectable at 14days after treatment and was higher than that in the other groups at 1, 3, and 7days. Intratumoral doxorubicin fluorescence was detected at all time points in the QuadraSphere group, but only at 1day after treatment in the TACE group. Hepatic arterial administration of doxorubicin-loaded QuadraSpheres enables the sustained release of doxorubicin to hepatic tumors.