Sodium Cholate Bile Acid-Stabilized Ferumoxytol-Doxorubicin-Lipiodol Emulsion for Transcatheter Arterial Chemoembolization of Hepatocellular Carcinoma.

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  • Additional Information
    • Source:
      Publisher: Society of Cardiovascular and Interventional Radiology Country of Publication: United States NLM ID: 9203369 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1535-7732 (Electronic) Linking ISSN: 10510443 NLM ISO Abbreviation: J Vasc Interv Radiol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Reston, Va. : Society of Cardiovascular and Interventional Radiology, c1990-
    • Subject Terms:
      Chemoembolization, Therapeutic*; Antibiotics, Antineoplastic/*administration & dosage ; Carcinoma, Hepatocellular/*therapy ; Contrast Media/*administration & dosage ; Doxorubicin/*administration & dosage ; Ethiodized Oil/*administration & dosage ; Ferrosoferric Oxide/*administration & dosage ; Liver Neoplasms, Experimental/*therapy ; Sodium Cholate/*administration & dosage; Animals ; Antibiotics, Antineoplastic/chemistry ; Apoptosis/drug effects ; Carcinoma, Hepatocellular/diagnostic imaging ; Carcinoma, Hepatocellular/pathology ; Cell Line, Tumor ; Contrast Media/chemistry ; Doxorubicin/chemistry ; Drug Liberation ; Drug Stability ; Emulsions ; Ferrosoferric Oxide/chemistry ; Infusions, Intra-Arterial ; Kinetics ; Liver Neoplasms, Experimental/diagnostic imaging ; Liver Neoplasms, Experimental/pathology ; Magnetic Resonance Imaging ; Multimodal Imaging ; Rats, Sprague-Dawley ; Sodium Cholate/chemistry ; Tomography, X-Ray Computed
    • Abstract:
      Purpose: To develop bile acid-stabilized multimodal magnetic resonance (MR) imaging and computed tomography (CT)-visible doxorubicin eluting lipiodol emulsion for transarterial chemoembolization of hepatocellular carcinoma (HCC).
      Materials and Methods: Ferumoxytol, a US Food and Drug Administration-approved iron oxide nanoparticle visible under MR imaging was electrostatically complexed with doxorubicin (DOX). An amphiphilic bile acid, sodium cholate (SC), was used to form a stable dispersion of ferumoxytol-DOX complex in lipiodol emulsion. Properties of the fabricated emulsion were characterized in various component ratios. Release kinetics of DOX were evaluated for the chemoembolization applications. Finally, in vivo multimodal MR imaging/CT imaging properties and potential therapeutic effects upon intra-arterial (IA) infusion bile acid-stabilized ferumoxytol-DOX-lipiodol emulsion were evaluated in orthotopic McA-Rh7777 HCC rat models.
      Results: DOX complexed with ferumoxytol through electrostatic interaction. Amphiphilic SC bile acid at the interface between the aqueous ferumoxytol-DOX complexes and lipiodol enabled a sustained DOX release (17.2 ± 1.6% at 24 hours) at an optimized component ratio. In McA Rh7777 rat HCC model, IA-infused emulsion showed a significant contrast around tumor in both T2-weighted MR imaging and CT images (P = .044). Hematoxylin and eosin and Prussian blue staining confirmed the local deposition of IA-infused SC bile acid-stabilized emulsion in the tumor. The deposited emulsion induced significant increases in TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) stain-positive cancer cell apoptosis compared to those in a group treated with the nonstabilized emulsion.
      Conclusions: SC bile acid-stabilized ferumoxytol-DOX-lipiodol emulsion demonstrated sustained drug release and multimodal MR imaging/CT imaging capabilities. The new lipiodol-based formulation may enhance the therapeutic efficacy of chemoembolization in HCC.
      (Copyright © 2020 SIR. Published by Elsevier Inc. All rights reserved.)
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    • Grant Information:
      R01 CA218659 United States CA NCI NIH HHS; R01 EB026207 United States EB NIBIB NIH HHS
    • Accession Number:
      0 (Antibiotics, Antineoplastic)
      0 (Contrast Media)
      0 (Emulsions)
      8008-53-5 (Ethiodized Oil)
      80168379AG (Doxorubicin)
      NU3Y4CCH8Z (Sodium Cholate)
      XM0M87F357 (Ferrosoferric Oxide)
    • Publication Date:
      Date Created: 20200811 Date Completed: 20201124 Latest Revision: 20211002
    • Publication Date:
      20231215
    • Accession Number:
      PMC7541531
    • Accession Number:
      10.1016/j.jvir.2020.01.026
    • Accession Number:
      32773247