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 |
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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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Management of bone metastasis is becoming increasingly important. We investigated the antitumor effects and safety of gelatin hydrogel microspheres incorporating cisplatin, which we developed as a sustained release system without harmful substances. 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.</description><identifier>ISSN: 0736-0266</identifier><identifier>EISSN: 1554-527X</identifier><identifier>DOI: 10.1002/jor.24874</identifier><identifier>PMID: 33030789</identifier><language>eng</language><publisher>United States</publisher><subject>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</subject><ispartof>Journal of orthopaedic research, 2021-03, Vol.39 (3), p.525-535</ispartof><rights>2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC</rights><rights>2020 Orthopaedic Research Society. 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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. 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 < 0.05). Local administration of GM‐CDDP significantly reduced loss of body weight and elevation of blood urea nitrogen compared with the systemic administration of free CDDP (p < .05). The current study suggests that local administration of GM‐CDDP achieves higher antitumor effects with a potential for lesser side effects compared with local or systemic administration of free CDDP.
Management of bone metastasis is becoming increasingly important. We investigated the antitumor effects and safety of gelatin hydrogel microspheres incorporating cisplatin, which we developed as a sustained release system without harmful substances. 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.</description><subject>Animals</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>antitumor drug</subject><subject>bone metastasis</subject><subject>Bone Neoplasms - drug therapy</subject><subject>Bone Neoplasms - secondary</subject><subject>Breast Neoplasms - pathology</subject><subject>CDDP</subject><subject>Cell Line, Tumor</subject><subject>Cisplatin - administration & dosage</subject><subject>Delayed-Action Preparations</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Female</subject><subject>Gelatin</subject><subject>gelatin hydrogel</subject><subject>Humans</subject><subject>Hydrogels</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Microspheres</subject><subject>sustained release</subject><issn>0736-0266</issn><issn>1554-527X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1LxDAQhoMo7rp68A9Ijnqom6Rpkh4X8RNhQRS8lbSdrlnapiatsuCPN2tXb8LAMMMzD8yL0Ckll5QQNl9bd8m4knwPTWmS8Chh8nUfTYmMRUSYEBN05P2aECIpU4doEsckJlKlU_S1wK39gBr3tjOFDt2B7htoe1xZh3PbAm6g1z4UeDx4066wxiuodW9a_LYpnQ0DNm1hXWfddrvChfHdCGgfaD-Ec9NCiR3UEETYb3wPzTE6qHTt4WTXZ-jl5vr56i56XN7eXy0eoyI8w6NcJKQsNRGpyvM8ESCFUoLKmFOqFIvDhqpEVlqLhMeElTqAFFjJK1akOY9n6Hz0ds6-D-D7rDG-gLrWLdjBZ4zzlAmWShrQixEtnPXeQZV1zjTabTJKsm3YWQg7-wk7sGc77ZA3UP6Rv-kGYD4Cn6aGzf-m7GH5NCq_AXfCiso</recordid><startdate>202103</startdate><enddate>202103</enddate><creator>Kanda, Yutaro</creator><creator>Kakutani, Kenichiro</creator><creator>Yurube, Takashi</creator><creator>Zhang, Zhongying</creator><creator>Miyazaki, Shingo</creator><creator>Kakiuchi, Yuji</creator><creator>Takeoka, Yoshiki</creator><creator>Tsujimoto, Ryu</creator><creator>Miyazaki, Kunihiko</creator><creator>Kawamoto, Teruya</creator><creator>Takada, Toru</creator><creator>Hoshino, Yuichi</creator><creator>Tabata, Yasuhiko</creator><creator>Kuroda, Ryosuke</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3007-361X</orcidid><orcidid>https://orcid.org/0000-0001-5538-5516</orcidid></search><sort><creationdate>202103</creationdate><title>A novel topical treatment for bone metastases using a gelatin hydrogel incorporating cisplatin as a sustained release system</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5544-b650dda0698bbb56e76886173411882356e1857faa654302da98b1e2d4f2c9b43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>antitumor drug</topic><topic>bone metastasis</topic><topic>Bone Neoplasms - drug therapy</topic><topic>Bone Neoplasms - secondary</topic><topic>Breast Neoplasms - pathology</topic><topic>CDDP</topic><topic>Cell Line, Tumor</topic><topic>Cisplatin - administration & dosage</topic><topic>Delayed-Action Preparations</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Female</topic><topic>Gelatin</topic><topic>gelatin hydrogel</topic><topic>Humans</topic><topic>Hydrogels</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Microspheres</topic><topic>sustained release</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kanda, Yutaro</creatorcontrib><creatorcontrib>Kakutani, Kenichiro</creatorcontrib><creatorcontrib>Yurube, Takashi</creatorcontrib><creatorcontrib>Zhang, Zhongying</creatorcontrib><creatorcontrib>Miyazaki, Shingo</creatorcontrib><creatorcontrib>Kakiuchi, Yuji</creatorcontrib><creatorcontrib>Takeoka, Yoshiki</creatorcontrib><creatorcontrib>Tsujimoto, Ryu</creatorcontrib><creatorcontrib>Miyazaki, Kunihiko</creatorcontrib><creatorcontrib>Kawamoto, Teruya</creatorcontrib><creatorcontrib>Takada, Toru</creatorcontrib><creatorcontrib>Hoshino, Yuichi</creatorcontrib><creatorcontrib>Tabata, Yasuhiko</creatorcontrib><creatorcontrib>Kuroda, Ryosuke</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of orthopaedic research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kanda, Yutaro</au><au>Kakutani, Kenichiro</au><au>Yurube, Takashi</au><au>Zhang, Zhongying</au><au>Miyazaki, Shingo</au><au>Kakiuchi, Yuji</au><au>Takeoka, Yoshiki</au><au>Tsujimoto, Ryu</au><au>Miyazaki, Kunihiko</au><au>Kawamoto, Teruya</au><au>Takada, Toru</au><au>Hoshino, Yuichi</au><au>Tabata, Yasuhiko</au><au>Kuroda, Ryosuke</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A novel topical treatment for bone metastases using a gelatin hydrogel incorporating cisplatin as a sustained release system</atitle><jtitle>Journal of orthopaedic research</jtitle><addtitle>J Orthop Res</addtitle><date>2021-03</date><risdate>2021</risdate><volume>39</volume><issue>3</issue><spage>525</spage><epage>535</epage><pages>525-535</pages><issn>0736-0266</issn><eissn>1554-527X</eissn><abstract>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 < 0.05). Local administration of GM‐CDDP significantly reduced loss of body weight and elevation of blood urea nitrogen compared with the systemic administration of free CDDP (p < .05). The current study suggests that local administration of GM‐CDDP achieves higher antitumor effects with a potential for lesser side effects compared with local or systemic administration of free CDDP.
Management of bone metastasis is becoming increasingly important. We investigated the antitumor effects and safety of gelatin hydrogel microspheres incorporating cisplatin, which we developed as a sustained release system without harmful substances. 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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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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