A novel topical treatment for bone metastases using a gelatin hydrogel incorporating cisplatin as a sustained release system

Management of bone metastasis is becoming increasingly important. Thus, local and systemic treatment options have been developed for control. Although systemic administration of anticancer agents is effective for bone metastasis, it is often stopped because of poor general conditions or side effects...

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Veröffentlicht in:Journal of orthopaedic research 2021-03, Vol.39 (3), p.525-535
Hauptverfasser: Kanda, Yutaro, Kakutani, Kenichiro, Yurube, Takashi, Zhang, Zhongying, Miyazaki, Shingo, Kakiuchi, Yuji, Takeoka, Yoshiki, Tsujimoto, Ryu, Miyazaki, Kunihiko, Kawamoto, Teruya, Takada, Toru, Hoshino, Yuichi, Tabata, Yasuhiko, Kuroda, Ryosuke
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container_issue 3
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container_title Journal of orthopaedic research
container_volume 39
creator Kanda, Yutaro
Kakutani, Kenichiro
Yurube, Takashi
Zhang, Zhongying
Miyazaki, Shingo
Kakiuchi, Yuji
Takeoka, Yoshiki
Tsujimoto, Ryu
Miyazaki, Kunihiko
Kawamoto, Teruya
Takada, Toru
Hoshino, Yuichi
Tabata, Yasuhiko
Kuroda, Ryosuke
description Management of bone metastasis is becoming increasingly important. Thus, local and systemic treatment options have been developed for control. Although systemic administration of anticancer agents is effective for bone metastasis, it is often stopped because of poor general conditions or side effects. Therefore, it is highly desirable to develop a more effective and safer local treatment for bone metastasis. The purpose of the current study was to investigate the antitumor effects and safety of gelatin hydrogel microspheres incorporating cisplatin (GM‐CDDP), which we developed as a sustained release system without harmful substances. First, we assessed GM‐CDDP for its in vitro degradability and potential for sustained release. Second, in vivo antitumor and side effects were evaluated using a murine bone metastasis model of MDA‐MB‐231 human breast cancer cells incorporating GFP. In vitro, initial bursts were observed within 2 h and CDDP was released gradually with gelatin hydrogel degradation, which reached 100% at 48 h. In vivo, local administration of GM‐CDDP (2 mg/kg) significantly suppressed tumor growth and bone osteolysis compared with the control, and local and systemic administration of free CDDP (2 mg/kg; p 
doi_str_mv 10.1002/jor.24874
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Thus, local and systemic treatment options have been developed for control. Although systemic administration of anticancer agents is effective for bone metastasis, it is often stopped because of poor general conditions or side effects. Therefore, it is highly desirable to develop a more effective and safer local treatment for bone metastasis. The purpose of the current study was to investigate the antitumor effects and safety of gelatin hydrogel microspheres incorporating cisplatin (GM‐CDDP), which we developed as a sustained release system without harmful substances. First, we assessed GM‐CDDP for its in vitro degradability and potential for sustained release. Second, in vivo antitumor and side effects were evaluated using a murine bone metastasis model of MDA‐MB‐231 human breast cancer cells incorporating GFP. In vitro, initial bursts were observed within 2 h and CDDP was released gradually with gelatin hydrogel degradation, which reached 100% at 48 h. 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Local administration of gelatin hydrogel microspheres incorporating cisplatin suppressed tumor growth and bone osteolysis with less side effects, compared to the control, and local and systemic administration of free cisplatin. 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Thus, local and systemic treatment options have been developed for control. Although systemic administration of anticancer agents is effective for bone metastasis, it is often stopped because of poor general conditions or side effects. Therefore, it is highly desirable to develop a more effective and safer local treatment for bone metastasis. The purpose of the current study was to investigate the antitumor effects and safety of gelatin hydrogel microspheres incorporating cisplatin (GM‐CDDP), which we developed as a sustained release system without harmful substances. First, we assessed GM‐CDDP for its in vitro degradability and potential for sustained release. Second, in vivo antitumor and side effects were evaluated using a murine bone metastasis model of MDA‐MB‐231 human breast cancer cells incorporating GFP. In vitro, initial bursts were observed within 2 h and CDDP was released gradually with gelatin hydrogel degradation, which reached 100% at 48 h. 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Local administration of gelatin hydrogel microspheres incorporating cisplatin suppressed tumor growth and bone osteolysis with less side effects, compared to the control, and local and systemic administration of free cisplatin. Therefore, this system could be the next therapeutic strategy for local management of bone metastasis.</abstract><cop>United States</cop><pmid>33030789</pmid><doi>10.1002/jor.24874</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-3007-361X</orcidid><orcidid>https://orcid.org/0000-0001-5538-5516</orcidid><oa>free_for_read</oa></addata></record>
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source MEDLINE; Wiley Online Library Journals Frontfile Complete; Wiley Free Content
subjects Animals
Antineoplastic Agents - administration & dosage
antitumor drug
bone metastasis
Bone Neoplasms - drug therapy
Bone Neoplasms - secondary
Breast Neoplasms - pathology
CDDP
Cell Line, Tumor
Cisplatin - administration & dosage
Delayed-Action Preparations
Drug Screening Assays, Antitumor
Female
Gelatin
gelatin hydrogel
Humans
Hydrogels
Mice
Mice, Inbred BALB C
Mice, Nude
Microspheres
sustained release
title A novel topical treatment for bone metastases using a gelatin hydrogel incorporating cisplatin as a sustained release system
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