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Combination of Doxorubicin and Antiangiogenic Agents in Drug-Eluting Beads: In Vitro Loading and Release Dynamics in View of a Novel Therapeutic Approach for Hepatocellular Carcinoma

  • Laboratory Investigation
  • Interventional Oncology
  • Published:
CardioVascular and Interventional Radiology Aims and scope Submit manuscript

Abstract

Purpose

Antiangiogenic agents have been used for many years as a first-line systemic treatment for advanced HCC. Embolization with cytostatic drugs on the other hand is the first-line treatment for intermediate HCC. The two types of drugs have not been combined for intraarterial delivery yet. The loading and release dynamics and the in vitro effect of their combination are tested in this experimental study.

Materials and Methods

Drug-eluting beads were loaded with doxorubicin, sunitinib and sunitinib analogue piperazine (SAP) alone and with their combinations. Diameter change, loading, release, and effect in cellular proliferation were assessed.

Results

The average microsphere diameter after loading was 473.7 µm (μm) for Doxorubicin, 388.4 μm for Sunitinib, 515.5 μm for SAP, 414.8 μm for the combination Doxorubicin/Sunitinib and 468.8 μm for the combination Doxorubicin /SAP. Drug release in 0.9% NaCl was 10% for Doxorubicin, 49% for Sunitinib, 25% for SAP, 20%/18% for the combination Doxorubicin/Sunitinib, and 18%/23% for the combination Doxorubicin/SAP whereas in human plasma it was 56%, 27%, 13%, 76%/63% and 62%/15%, respectively. The mean concentration of Doxorubicin that led to inhibition of 50% of cellular proliferation in an HCC Huh7 cell line was 163.1 nM (nM), for Sunitinib 10.3 micromolar (μΜ), for SAP 16.7 μΜ, for Doxorubicin/Sunitinib 222.4 nM and for Doxorubicin/SAP 275 nM.

Conclusions

Doxorubicin may be combined with antiangiogenic drugs with satisfactory in vitro loading and release outcomes and effect on cellular lines.

Graphical Abstract

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Abbreviations

HCC:

Hepatocellular carcinoma

SAP:

Sunitinib Analogue Piperazine

μM:

Micromolar

nM:

Nanomolar

μm:

Micrometres

nm:

Nanometres

TACE:

Transarterial chemoembolization

TKIs:

Tyrosine kinase inhibitors

HPLC:

High-performance liquid chromatography

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Funding

This study was not supported by any funding.

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Author notes

  1. Constantin Tamvakopoulos and Achilles Chatziioannou have contributed equally to this work.

Authors and Affiliations

  1. The 1st Department of Radiology, Areteion University Hospital, Medical School, National and Kapodistrian University of Athens, 76, Vas. Sophias Ave, 11528, Athens, Greece

    Miltiadis Krokidis & Achilles Chatziioannou

  2. Department of Diagnostic, Interventional and Pediatric Radiology (DIPR), Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

    Miltiadis Krokidis

  3. Clinical, Experimental Surgery, & Translational Research Center, Division of Pharmacology-Pharmacotechnology, Biomedical Research Foundation Academy of Athens, Athens, Greece

    Danae Fakitsa, Theodoros Karampelas & Constantin Tamvakopoulos

  4. The 2nd Department of Radiology, University of Athens, “Attikon” Hospital, 1 Rimini Str, Chaidari, 12462, Athens, Greece

    Katerina Malagari

  5. Department of Materials Science and Engineering, University of Ioannina, Ioannina, Greece

    Demosthenes Fokas

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Krokidis, M., Fakitsa, D., Malagari, K. et al. Combination of Doxorubicin and Antiangiogenic Agents in Drug-Eluting Beads: In Vitro Loading and Release Dynamics in View of a Novel Therapeutic Approach for Hepatocellular Carcinoma. Cardiovasc Intervent Radiol (2024). https://doi.org/10.1007/s00270-024-03714-z

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