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

Abstract

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.

350–560 μm gelatin sponge particles combined with transcatheter arterial chemoembolization for the treatment of elderly hepatocellular carcinoma

“…GSPs has the sustained effects of chemotherapy drugs, which make the less chemotherapy drugs maintain longer period of drug concentration, and this may be one of the reasons to achieve better efficacy in this study. [27] …”

“…Secondly, our previous study had documented the significantly higher chemotherapeutic drug concentration in tumor tissue and lower chemotherapeutic drugs in peripheral plasma compared with intra-arterial infusion in the VX2 animals model treated with GSMs-TACE. [27] That may be one of therapeutic mechanisms of GSMs-TACE for HCC.…”

New modalities of treatment for hepatocellular carcinoma

“…The results suggested the usage of GSMs-TACE comparing to c-TACE group and hepatic arterial infusion (HAI) group have higher concentration of chemotherapy drug with slow drug release. 31 Human research also showed good tolerance on GSMs and the OS rate was 100% in six months and 87.5%, in one year. 32 Other parallel studies confirmed the safety and effectiveness of gelatin sponge particle TACE for treatment of the Barcelona-Clinic Liver Cancer (BCLC) stage B HCC patients.…”

Transarterial chemoembolization combined with Huaier granule for the treatment of primary hepatic carcinoma

“…Drugs delivered directly by the microspheres increase tumor necrosis and response rate. [6,7] The domestically produced 350 to 560 μm GSPs used in this study have previously been used for regional embolization in the treatment of HCC. Treatment resulted in tumor necrosis and shrinking, rapid recovery of liver function, and good short-term effectiveness.…”