Development of in Situ Forming Thermosensitive Hydrogel for Radiotherapy Combined with Chemotherapy in a Mouse Model of Hepatocellular Carcinoma

详细信息    查看全文

• 作者：Cheng-Liang Peng ; Ying-Hsia Shih ; Kuo-Sheng Liang ; Ping-Fang Chiang ; Chung-Hsin Yeh ; I-Chang Tang ; Cheng-Jung Yao ; Shin-Yi Lee ; Tsai-Yueh Luo ; Ming-Jium Shieh
• 刊名：Molecular Pharmaceutics
• 出版年：2013
• 出版时间：May 6, 2013
• 年：2013
• 卷：10
• 期：5
• 页码：1854-1864
• 全文大小：711K
• 年卷期：v.10,no.5(May 6, 2013)
• ISSN：1543-8392

文摘

This study evaluated a system for local cancer radiotherapy combined with chemotherapy. The delivery system is a thermosensitive hydrogel containing a therapeutic radionuclide (¹⁸⁸Re-Tin colloid) and a chemotherapeutic drug (liposomal doxorubicin). The thermosensitive PCL-PEG-PCL copolymer was designed to spontaneously undergo a sol鈥揼el phase transition in response to temperature, remaining liquid at room temperature and rapidly forming a gel at body temperature. A scanning electron microscope was used to observe the microstructure of the fully loaded hydrogel. Release of radionuclide and doxorubicin from the hydrogel was slow, and the system tended to remain stable for at least 10 days. After the intratumoral administration of Lipo-Dox/¹⁸⁸Re-Tin hydrogel in mice with hepatocellular carcinoma (HCC), its retention by the tumor, spatiotemporal distribution, and therapeutic effect were evaluated. The residence time in the tumor was significantly longer for ¹⁸⁸Re-Tin loaded hydrogel than for Na ¹⁸⁸Re perrhenate (Na ¹⁸⁸ReO₄). The hydrogel after thermal transition kept the radionuclide inside the tumor, whereas free ¹⁸⁸Re perrhenate (¹⁸⁸ReO₄) diffused quickly from the tumor. The tumor growth was more profoundly inhibited by treatment with Lipo-Dox/¹⁸⁸Re-Tin hydrogel (with up to 80% regression of well-established tumors on day 32) than treatment with either ¹⁸⁸Re-Tin hydrogel or Lipo-Dox hydrogel. Therefore, this injectable and biodegradable hydrogel may offer the advantage of focusing radiotherapy and chemotherapy locally to maximize their effects on hepatocellular carcinoma.

Keywords:

thermally responsive material; chemotherapy; radiotherapy; drug delivery; hepatocellular carcinoma