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Synthesis and characterization of image-able polyvinyl alcohol microspheres for image-guided chemoembolization

  • Biomaterials Synthesis and Characterization
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Abstract

Therapeutic embolization of blood vessels is a minimally invasive, catheter-based procedure performed with solid or liquid emboli to treat bleeding, vascular malformations, and vascular tumors. Hepatocellular carcinoma (HCC) affects about half a million people per year. When unresectable, HCC is treated with embolization and local drug therapy by transarterial chemoembolization (TACE). For TACE, drug eluting beads (DC Bead®) may be used to occlude or reduce arterial blood supply and deliver chemotherapeutics locally to the tumor. Although this treatment has been shown to be safe and to improve patient survival, the procedure lacks imaging feedback regarding the location of embolic agent and drug coverage. To address this shortcoming, herein we report the synthesis and characterization of image-able drug eluting beads (iBeads) from the commercial DC Bead® product. Two different radiopaque beads were synthesized. In one approach, embolic beads were conjugated with 2,3,5-triiodobenzyl alcohol in the presence of 1,1′-carbonyldiimidazol to give iBead I. iBead II was synthesized with a similar approach but instead using a trimethylenediamine spacer and 2,3,5-triiodobenzoic acid. Doxorubicin was loaded into the iBeads II using a previously reported method. Size and shape of iBeads were evaluated using an upright microscope and their conspicuity assessed using a clinical CT and micro-CT. Bland and Dox-loaded iBeads II visualized with both clinical CT and microCT. Under microCT, individual bland and Dox loaded beads had a mean attenuation of 7904 ± 804 and 11,873.96 ± 706.12 HU, respectively. These iBeads have the potential to enhance image-guided TACE procedures by providing localization of embolic-particle and drug.

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Acknowledgments

This research was supported by the Center for Interventional Oncology in the Intramural Research Program of the National Institutes of Health (NIH). NIH and Biocompatibles UK Ltd, a BTG International group company have a Cooperative Research and Development Agreement. C.G.J. was supported by the Imaging Sciences Training Program of the National Institutes of Health. We would like to thank Belhu Metaferia, for his advice and useful discussions.

Conflict of interest

Ayele H. Negussie, Carmen Gacchina Johnson, Gert Storm, Karun V. Sharma and Bradford J. Wood do not have any forms of conflicts of interest. The mention of commercial products, their source, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the National Institutes of Health. The authors alone are responsible for the content and opinions of the paper. NIH and Biocompatibles UK Ltd, a BTG International group company have a cooperative research and development agreement.

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Authors and Affiliations

  1. Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, 20814, USA

    Ayele H. Negussie, Matthew R. Dreher, Carmen Gacchina Johnson, Karun V. Sharma & Bradford J. Wood

  2. Bioccompatibles UK Ltd., Farnham Business Park, Weydon Lane, Farnham, Survey, GU98QL, UK

    Yiqing Tang & Andrew L. Lewis

  3. Department of Targeted Therapeutics, MIRA Institute, University of Twente, Enschede, The Netherlands

    Ayele H. Negussie & Gert Storm

  4. Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands

    Gert Storm

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  1. Ayele H. Negussie
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Negussie, A.H., Dreher, M.R., Johnson, C.G. et al. Synthesis and characterization of image-able polyvinyl alcohol microspheres for image-guided chemoembolization. J Mater Sci: Mater Med 26, 198 (2015). https://doi.org/10.1007/s10856-015-5530-3

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