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Investigation of the local delivery of an intelligent chitosan-based 188Re thermosensitive in situ-forming hydrogel in an orthotopic hepatoma-bearing rat model

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Abstract

In this study, in vitro and in vivo evaluations of the local delivery of 188Re-Tin colloid and doxorubicin (Dox) through chitosan (C)-based thermosensitive in situ-forming hydrogels by intratumoral injection in an orthotopic hepatoma-bearing rat model were carried out. Selective internal radiation therapy has been increasingly used as an alternative therapy option for hepatocellular carcinoma (HCC) and combined with biodegradable drug carrier systems to improve drug delivery and systemic toxicity. The C-based thermosensitive hydrogel (C/GP), an injectable thermogelling solution crosslinked between C and β-glycerophosphate (GP), was induced as an implanted carrier to combine the 188Re-Tin colloid and Dox as a novel treatment strategy. The compounded hydrogel characteristics, including the gelation time, controlled release of Dox, and morphology, were examined. In the animal study, the biodistribution, scintigraphy, therapeutic efficacy, and histopathology were also evaluated. The characterization results reveal that C/GP/Dox hydrogels have similar gelation times of 4–4.5 min and pore sizes of as small as 10 μm compared with C/GP hydrogels. The C/GP/Dox/188Re-Tin colloids have the longest release time for Dox at 2–3 days. In the in vivo experiments, both the biodistribution and scintigraphy studies have the highest hydrogel uptakes in the tumor at different time points, as well as localized radioactivities for a certain time. The therapeutic evaluation indicates that C/GP/Dox/188Re-Tin colloids can more significantly inhibit tumors compared with the control group at 2 and 4 weeks post-treatment. These results indicate that this novel treatment system is a promising option for inoperable HCC.

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Acknowledgments

This study was supported by a grant from the National Science Council of Taiwan under No. NSC 98-2314-B-166-001-MY3.

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Authors and Affiliations

  1. Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan

    Feng-Yun J. Huang

  2. Institute of Radiological Science, Central Taiwan University of Science and Technology, 11, Po-Tze Lane, Takun, Taichung, Taiwan

    Guo-Yi Gan, Ling-Kuen Huang, Jhen-Jie Hong & Bor-Tsung Hsieh

  3. Department of Nuclear Medicine, Taichung Veterans General Hospital, Taiwan Center of General Education, Central Taiwan University of Science and Technology, Taichung, Taiwan

    Wan-Yu Lin

  4. Isotope Application Division, Institute of Nuclear Energy Research, Lung-tan, Taiwan

    Tsai-Yueh Luo

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  1. Feng-Yun J. Huang
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Correspondence to Bor-Tsung Hsieh.

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Feng-Yun J. Huang and Guo-Yi Gan contributed equally to this work.

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Huang, FY.J., Gan, GY., Lin, WY. et al. Investigation of the local delivery of an intelligent chitosan-based 188Re thermosensitive in situ-forming hydrogel in an orthotopic hepatoma-bearing rat model. J Radioanal Nucl Chem 299, 31–40 (2014). https://doi.org/10.1007/s10967-013-2742-1

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