Tumor Biology

, Volume 35, Issue 11, pp 10905–10910 | Cite as

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

  • Yue Wei Zhang
  • Jin Ao
  • Ying Liu
  • Ming Xi Qiao
  • Xue Ling Yang
  • Shun Xiong Tang
  • Chuang Li
  • Ke Xu
Research Article


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.


VX2 model Hepatocellular carcinoma Chemoembolization Gelatin sponge microparticles Epirubicin Pharmacokinetics 


Conflict of interest

We declare that we have no conflict of interest.


  1. 1.
    Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C et al. .v1.0, Cancer incidence and mortality worldwide: IARC CancerBase No. 11 [Internet]. 2013.Google Scholar
  2. 2.
    Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003;362:1907–17.PubMedCrossRefGoogle Scholar
  3. 3.
    Kruskal JB, Hlatky L, Hahnfeldt P, Teramoto K, Stokes KR, Clouse ME. In vivo and in vitro analysis of the effectiveness of doxorubicin combined with temporary arterial occlusion in liver tumors. J Vasc Interv Radiol. 1993;4:741–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Konno T, Maeda H, Iwai K, Tashiro S, Maki S, Morinaga T, et al. Effect of arterial administration of high molecular weight anticancer agent SMANCS with lipid lymphographic agent on hepatoma: a preliminary report. Eur J Cancer Chn Oncol. 1983;19:1058–65.Google Scholar
  5. 5.
    Nakamura H, Tanaka T, Hori S, Yoshioka H, Kuroda C, Okamura J, et al. Transcatheter embolization of hepatocellular carcinoma: assessment of efficacy in cases of resection following embolization. Radiology. 1983;147:401–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Raoul JL, Heresbach D, Bretagne JF, Ferrer DB, Duvauferrier R, Bourguet P, et al. Chemoembolization of hepatocellular carcinomas. A study of the biodistribution and pharmacokinetics of doxorubicin. Cancer. 1992;70:585–90.PubMedCrossRefGoogle Scholar
  7. 7.
    Kerr DJ. Microparticulate drug delivery systems as an adjunct to cancer treatment. Cancer Drug Deliv. 1987;4:55–61.PubMedCrossRefGoogle Scholar
  8. 8.
    Lewis AL, Gonzalez MV, Lloyd AW, Hall B, Tang Y, Willis SL, et al. DC bead: in vitro characterization of a drug-delivery device for transarterial chemoembolization. J Vasc Interv Radiol. 2006;17:335–42.PubMedCrossRefGoogle Scholar
  9. 9.
    Varela M, Real MI, Burrel M, Forner A, Sala M, Brunet M, et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol. 2007;46:474–81.PubMedCrossRefGoogle Scholar
  10. 10.
    Li C, Zhang Y, Zhou J, Zhao G, Tang S. Therapeutic effect and tolerability of gelatin sponge particle-mediated chemoembolization for colorectal liver metastases: a retrospective study. World J Surg Oncol. 2013;11:222.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Zhang YW, Liu Y. Transcatheter arterial chemoembolization of hepatocellular carcinoma with 350 ~ 560 μm Gelatin sponge particles: efficacy, tumour response and survival. Chin J Hepatol. 2013;21:637–8.Google Scholar
  12. 12.
    Zhou J, Zhang Y, Zhao G, Liu Y, Li C, Tang S, et al. The preliminary study of recombinant adenovirus p53 combined with transarterial embolization with particles for advanced hepatocellular carcinoma. Natl Med J Chin. 2014;94(9):660–3.Google Scholar
  13. 13.
    Tabata Y, Ikada Y. Synthesis of gelatin particles containing interferon. Pharm Res. 1989;6:422–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Konishi M, Tabata Y, Kariya M, Hosseinkhani H, Suzuki A, Fukuhara K, et al. In vivo anti-tumor effect of dual release of cisplatin and adriamycin from biodegradable gelatin hydrogel. J Control Release. 2005;103:7–19.PubMedCrossRefGoogle Scholar
  15. 15.
    Ni Y, Wang H, Chen F, Li J, DeKeyzer F, Feng Y, et al. Tumor models and specific contrast agents for small animal imaging in oncology[J]. Methods. 2009;48:125–38.PubMedCrossRefGoogle Scholar
  16. 16.
    Munck JN, Riggi M, Rougier P, Chabot GG, Ramirez LH, Zhao Z, et al. Pharmacokinetic and pharmacodynamic advantages of pirarubicin over adriamycin after intraarterial hepatic administration in the rabbit VX2 tumor model. Cancer Res. 1993;53:1550–4.PubMedGoogle Scholar
  17. 17.
    Guo WH, Xiong YQ. Comparison of pharmacokinetic characteristics of injecting hydroxycamptothecine through hepatic artery and auricular vein of rabbit. Chinese J Cancer Prev Treat. 2007;14:1368–71.Google Scholar
  18. 18.
    Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208–36.PubMedCrossRefGoogle Scholar
  19. 19.
    Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 2003;37:429–42.PubMedCrossRefGoogle Scholar
  20. 20.
    Frei III E. In: Holland JF, Frei III E, editors. Cancer medicine. Philadelphia: Lea and Febiger; 1973. p. 717–30.Google Scholar
  21. 21.
    Hong K, Khwaja A, Liapi E, Torbenson MS, Georgiades CS, Geschwind JF. New intra-arterial drug delivery system for the treatment of liver cancer: preclinical assessment in a rabbit model of liver cancer. Clin Cancer Res. 2006;12:2563–7.PubMedCrossRefGoogle Scholar
  22. 22.
    van Malenstein H, Maleux G, Vandecaveye V, Heye S, Laleman W, van Pelt J, et al. A randomized phase II study of drug-eluting beads versus transarterial chemoembolization for unresectable hepatocellular carcinoma. Onkologie. 2011;34:368–76.PubMedCrossRefGoogle Scholar
  23. 23.
    Kruskal JB, Hlatky L, Hahnfeldt P, Teramoto K, Stokes KR, Clouse ME. In vivo and in vitro analysis of the effectiveness of doxorubicin combined with temporary arterial occlusion in liver tumors. JVIR. 1993;4:741–7.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Yue Wei Zhang
    • 1
  • Jin Ao
    • 2
  • Ying Liu
    • 3
  • Ming Xi Qiao
    • 4
  • Xue Ling Yang
    • 5
  • Shun Xiong Tang
    • 3
  • Chuang Li
    • 3
  • Ke Xu
    • 1
  1. 1.The First Affiliated Hospital of China Medical UniversityShenyangChina
  2. 2.Department of Interventional Radiologythe First Affiliated Hospital of Zunyi Medical UniversityZunyiChina
  3. 3.Department of Interventional RadiologyAffiliated Zhongshan Hospital of Dalian UniversityDalianChina
  4. 4.School of PharmacyShenyang Pharmaceutical UniversityShenyangChina
  5. 5.Department of Interventional OncologyTianjin Medical University Affiliated Cancer HospitalTianjinChina

Personalised recommendations