Pharmacokinetics of gelatin sponge microparticles in a rabbit VX2 liver tumor model of hepatic arterial chemoembolization

The objective of this study is to investigate pharmacokinetics of gelatin sponge microparticles (GSMs) combined with epirubicin in a rabbit VX2 liver tumor model of hepatic arterial chemoembolization (TACE). Eighteen successful models of VX2 in New Zealand white rabbits was established, which were divided into three groups randomly: HAI group (n = 6), the epirubicin solution (epirubicin 10 mg mixed with saline 10 ml into the hepatic artery); GSMs-TACE group (n = 6), GSMs (20 mg) mixed with epirubicin solution (1 mg/ml); c-TACE group (n = 6), epirubicin (10 mg) mixed with lipiodol (10 ml). Each rabbit was administrated epirubicin at dose adjusted for a 1 mg/kg. Samples were collected from femoral vein at 5, 10, 20, 30, 40, 60, 90, and 120 min after therapy after 120 min; rabbit was killed, and tumor and peritumoral normal liver tissue was cised. Epirubicin concentrations in plasma and tumor were measured. The epirubicin concentration in plasma was significantly lower in GSMs-TACE group than in HAI group. C _max in there groups after administration was 28.77 ± 7.15 μg/ml in c-TACE group, 83.84 ± 32.28 μg/ml in GSMs-TACE group, and 238.46 ± 23.44 μg/ml in HAI group at 5 min, respectively. The epirubicin concentration in tumor tissue was 53.06 ± 16.9 μg/g in c-TACE group, 44.49 ± 16.80 μg/g in the GSMs-TACE group, and 18.32 ± 8.30 μg/g in HAI group, respectively. Epirubicin concentration of GSMs-TACE group was significantly higher than that of HAI group (P < 0.05). The area under the curve (AUC) at 0–120 min in c-TACE, GSMs-TACE, and HAI groups were 1,815 ± 889.88, 3,416 ± 799.90, and 11,899 ± 2,717.17 μg min/ml, respectively. The AUC was lower in GSMs-TACE group than in HAI group (P < 0.05). Compared with HAI, GSMs-TACE has higher epirubicin concentrations in tumor and lower concentrations in plasma. The results show that GSMs-TACE has a feature of slow drug release—it may be one of the mechanisms of GSMs-TACE for HCC.