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

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Tumor Biology

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.

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We declare that we have no conflict of interest.

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Authors and Affiliations

  1. The First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning Province, China

    Yue Wei Zhang & Ke Xu

  2. Department of Interventional Radiology, the First Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou Province, China

    Jin Ao

  3. Department of Interventional Radiology, Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, Liaoning Province, China

    Ying Liu, Shun Xiong Tang & Chuang Li

  4. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning Province, China

    Ming Xi Qiao

  5. Department of Interventional Oncology, Tianjin Medical University Affiliated Cancer Hospital, Tianjin, 300060, China

    Xue Ling Yang

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  1. Yue Wei Zhang
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  2. Jin Ao
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  3. Ying Liu
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  8. Ke Xu
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Correspondence to Ke Xu.

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Yue Wei Zhang and Jin Ao contribute equally to this paper.

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Zhang, Y.W., Ao, J., Liu, Y. et al. Pharmacokinetics of gelatin sponge microparticles in a rabbit VX2 liver tumor model of hepatic arterial chemoembolization. Tumor Biol. 35, 10905–10910 (2014). https://doi.org/10.1007/s13277-014-2408-9

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  • DOI: https://doi.org/10.1007/s13277-014-2408-9

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