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 mu g/ml in c-TACE group, 83.84 +/- 32.28 mu g/ml in GSMs-TACE group, and 238.46 +/- 23.44 mu g/ml in HAI group at 5 min, respectively. The epirubicin concentration in tumor tissue was 53.06 +/- 16.9 mu g/g in c-TACE group, 44.49 +/- 16.80 mu g/g in the GSMs-TACE group, and 18.32 +/- 8.30 mu g/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 mu g 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.