Intrahepatic Arterial Delivery of Sorafenib Eluting Beads: A Pharmacokinetics Study

Eerdunbagena Ning (Haikou People's Hospital of Hainan Province)
Zhijun Wang (Interventional Radiography of China PLA General Hospital)

Abstract


 

Objective: To determine the slow-release effect of Sorafenib carried beads and its impact on the normal liver of dogs. Materials and Methods: (1) To obtain the maximal drug-carrying of beads, different sizes of beads (300-500 μm and 500-700 μm) were tried. Five bottles of different sizes of beads were added into 75% solution of Sorafenid-alcohol with different concentrations: Bottle a,50mg/20ml; Bottle b, 100mg/20ml; Bottle c, 100 mg/40ml; Bottle d, 200mg/40m; Bottle e, 250mg/50ml. (2) In vivo study: 12 dogs were randomly divided into four groups [group A, Sorafenib carried bead (500-700μm); group B, only bead (300-500μm) ; group C, Lipiodol-sorafenib and four dogs in each group. Each group was treated with TAE with emulsion mentioned above. Sorafenib concentration in plasma and liver tissue was determined with HPLC respectively. Result: (1) In vitro research: Sorafenib can be dissolved into 75% alcohol and the best concentration for drug-carrying was 100mg/20ml. (2) In vivo study: ① Compared with group D, the Cmax and AUC in plasma in group A and B has a significant statistics difference(p<0.05). ② Sorafenib concentration in liver tissue could be determined in group A in the 3rd day and even after one week while it could not be determined in group D. Conclusion: Sorafenib can be carried in DC-Bead in a certain condition. Compared with emulsion with Sorafenib and lipiodol, DC-bead has a definite slow-release function and it is superior to lipiodol.


Keywords


Sorafenib; Transcatheter arterial embolization; Drug bearing microsphere; Experimental study

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References


Song MJ, Park CH, Kim JD,etal.Drug-eluting bead carried with doxorubicin versus conventional Lipiodol-based transarterial chemoembolization in the treatment of hepatocellular carcinoma:a case-control study of Asian patients[J].Eur J Gastroenterol Hepatol, 2011; 23(6):521-7.

Seki N,Michel W,Jean MM,etal.Drug-eluting beads for liver embolization:concentration of doxorubicin in tissue and in beads in a pig model[J]. J Vasc Interv Radiol 2010; 21:259–267.

Andrew L, Lewis M,Victoria G,etal.Doxorubicin eluting beads – 1: Effects of drug carrying on bead characteristics and drug distribution[J]..J Mater Sci: Mater Med, 2007, 18:1691–1699.

M. Victoria G, Tang YQ, Gary J, etal.Doxorubicin eluting beads—2: methods for evaluating drug elution and in-vitro: in-vivo correlation[J]..J Mater Sci: Mater Med, 2008, 19:767–775.

Zhao Susu, Zhang Dongsheng and Lu Qin Research progress in the preparation and application of intravascular drug-eluting stents. Journal of Southeast University (Medical Edition), 2007,26 (5): 378-381.(in Chinese)

Guo Yanling, Feng Yumei. Progress in polymer research as anticancer drug carrier, Journal of Tianjin University of Science and Technology, 2004,19 (3): 11-14.(in Chinese)

Xu Kaiyuan, Zou Yinghua, Qi Xianrong, etc. Effect of adriamycin alginate beads embolization on angiogenesis of VX2 transplanted tumor in rabbit liver. Chinese Medical Imaging Technology. 2010,26 (2): 217-220. (in Chinese)

Lu Anlin, Xing Yujie, Wang Li, et al. The ability of rapamycin polylactide nanocomposites to affect the proliferation of vascular smooth muscle cells. China Tissue Engineering Research and Clinical Rehabilitation, 2010,14 (42): 7815-7818(in Chinese)

Yuan Huiyan, Zhang Yuan, Fan Tianyuan, Preparation and properties of ion exchange embolic beads and Pingyangmycincarried DC-bead, Journal of Peking University (Medical Edition), 2009, 41 (2): 217-220(in Chinese)

Kelvin H, Afsheen K, Eleni Li, et al.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; 12:2563-2567.

Hori S, Kobayashi K,Transcatheter Arterial Chemoembolization with Epirubicin-Carried Superabsorbent Polymer Beads for 135 Hepatocellular Carcinoma Patients: Single-Center Experience[J].Cardiovasc Intervent Radiol,2010 Sep 7. [Epub ahead of print].

Mahmood U.Can a clinically used chemoembolization vehicle improve transgene delivery [J]? Radiology, 2006, 240:619-620.

Richard E. J. Forster,Sharon A.Small,Yiqing Tang.Comparison of DC Bead-irinotecan and DC Bead-topotecan drug eluting beads for use in locoregional drug delivery to treat pancreatic cancer [J]. J Mater Sci: Mater Med, 2010, 21:2683–2690

Eyol A,Rachel R,Andrew L,etal.Chemoembolisation of rat colorectal liver metastases with drug eluting beads carried with irinotecan or doxorubicinClin Exp Metastasis (2008) 25:273–282. Clin Exp Metastasis,2008; 25:273–282.

Rachel R. , Yiqing T M. Victoria G,etal.Irinotecan drug eluting beads for use in chemoembolization:In vitro and in vivo evaluation of drug release propertieseuropean[J]. Journal of pharmaceutical sciences,2007,3 0: 7–14.

Renumathy D, DAVID A. K, CHARLES A. S,etal., Comparison of Conventional Transarterial Chemoembolization (TACE) and Chemoembolization With Doxorubicin Drug Eluting Beads (DEB) for Unresectable Hepatocelluar Carcinoma (HCC) [J]. Journal of Surgical Oncology 2010; 101:476–480

Kalayci,Marı′a V, Marı′a I ,Marta B.Chemoembolization of hepatocellular carcinoma with drug eluting beads: Efficacy and doxorubicin pharmacokinetics.Journal of Hepatology,2007, e,46:474–481.

Gadaleta CD, Ranieri G.Trans-arterial chemoembolization as a therapy for liver tumours: New clinical developments and suggestions forcombination with angiogenesis inhibitors[J].Crit Rev Oncol Hematol. 2010 Nov 8. [Epub ahead of print].

Adriana S, Chiara C, Romilda C,etal.Transcatheter arterial chemoembolization (TACE)in hepatocellular carcinoma (HCC): The role of angiogenesis and invasiveness. Am J Gastroenterol 2008; 103:914–921?

Fiorentini G.A new tool to enhance the efficacy of chemoembolization to treat primary and metastatic hepatic tumors[J]. Expert Opin Drug Deliv.2011;8(4):409-13.

Josep L, Sergio R, Vincenzo M,et al.Sorafenib in advanced hepatocellular carcinoma [J].N Engl J Med,2008,359(24):378-390.

Mahmood U.Can a clinically used chemoembolization vehicle improve transgene delivery? [J] Radiology, 2006, 240:619-620.

Liu L, Cao Y, Chen C, et al.Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5[J]. Cancer Res, 2006, 66(24):11851-11858.

Joachim K, Alfred S, Isabella K, etal.Drug-Carried Beads for the Treatment of Liver Cancer: Review of Current Results [J]..Cardiovasc Intervent Radiol (2008) 31:468–476.

[25]Katerina M, Mary P, Alexis K,etal.Prospective randomized comparison of chemoembolization with doxorubicin-eluting beads and bland embolization with beadBlock for hepatocellular carcinoma[J].Cardiovasc Intervent Radiol ,2010,33:541–551

Miyayama S, Yamashiro M, Okuda M, et al .Main Bile Duct Stricture Occurring After Transcatheter Arterial Chemoembolization for Hepatocellular.Carcinoma.Cardiovasc Intervent Radiol. 2010 Jan 8. [Epub ahead of print]

Wang MQ, Shao RH, Ye HY, et al. Investigation of bile duct injury after transca theter arter ial chemoembolization. Zhonghua Zhong Liu Za Zhi.2005, 27:609-612.

Barone M, Ettorre GC, Ladisa R , et al . Transcatheter arterial chemoembolization (TACE) in treatment of hepatocellular carcinoma. Hepatogastroenterology, 2003, 50:1832187.



DOI: https://doi.org/10.30564/jams.v3i2.1539

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