Expanding therapeutic utility of carfilzomib for breast cancer therapy by novel albumin-coated nanocrystal formulation
Carfilzomib (CFZ) is the second-in-class proteasome inhibitor with much improved efficacy and safety profiles over bortezomib in multiple myeloma patients. In expanding the utility of CFZ to solid cancer therapy, the poor aqueous solubility and in vivo instability of CFZ are considered major drawbac...
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| Veröffentlicht in: | Journal of controlled release 2019-05, Vol.302, p.148-159 |
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| creator | Park, Ji Eun Park, Joonyoung Jun, Yearin Oh, Yunseok Ryoo, Gongmi Jeong, Yoo-Seong Gadalla, Hytham H Min, Jee Sun Jo, Jung Hwan Song, Myung Geun Kang, Keon Wook Bae, Soo Kyung Yeo, Yoon Lee, Wooin |
| description | Carfilzomib (CFZ) is the second-in-class proteasome inhibitor with much improved efficacy and safety profiles over bortezomib in multiple myeloma patients. In expanding the utility of CFZ to solid cancer therapy, the poor aqueous solubility and in vivo instability of CFZ are considered major drawbacks. We investigated whether a nanocrystal (NC) formulation can address these issues and enhance anticancer efficacy of CFZ against breast cancer. The surface of NC was coated with albumin in order to enhance the formulation stability and drug delivery to tumors via interactions with albumin-binding proteins located in and near cancer cells. The novel albumin-coated NC formulation of CFZ (CFZ-alb NC) displayed improved metabolic stability and enhanced cellular interactions, uptake and cytotoxic effects in breast cancer cells in vitro. Consistently, CFZ-alb NC showed greater anticancer efficacy in a murine 4T1 orthotopic breast cancer model than the currently used cyclodextrin-based formulation. Overall, our results demonstrate the potential of CFZ-alb NC as a viable formulation for breast cancer therapy. |
| doi_str_mv | 10.1016/j.jconrel.2019.04.006 |
| format | Article |
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In expanding the utility of CFZ to solid cancer therapy, the poor aqueous solubility and in vivo instability of CFZ are considered major drawbacks. We investigated whether a nanocrystal (NC) formulation can address these issues and enhance anticancer efficacy of CFZ against breast cancer. The surface of NC was coated with albumin in order to enhance the formulation stability and drug delivery to tumors via interactions with albumin-binding proteins located in and near cancer cells. The novel albumin-coated NC formulation of CFZ (CFZ-alb NC) displayed improved metabolic stability and enhanced cellular interactions, uptake and cytotoxic effects in breast cancer cells in vitro. Consistently, CFZ-alb NC showed greater anticancer efficacy in a murine 4T1 orthotopic breast cancer model than the currently used cyclodextrin-based formulation. Overall, our results demonstrate the potential of CFZ-alb NC as a viable formulation for breast cancer therapy.</description><identifier>ISSN: 0168-3659</identifier><identifier>EISSN: 1873-4995</identifier><identifier>DOI: 10.1016/j.jconrel.2019.04.006</identifier><identifier>PMID: 30954620</identifier><language>eng</language><publisher>Netherlands</publisher><subject>albumins ; breast neoplasms ; cytotoxicity ; drugs ; mice ; myeloma ; nanocrystals ; neoplasm cells ; patients ; proteasome inhibitors ; solubility ; therapeutics</subject><ispartof>Journal of controlled release, 2019-05, Vol.302, p.148-159</ispartof><rights>Copyright © 2019 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c481t-25ed51e2d9978cdc8f926419f390e8ce6c65f38094a71ab8f9befe28c516d9323</citedby><cites>FETCH-LOGICAL-c481t-25ed51e2d9978cdc8f926419f390e8ce6c65f38094a71ab8f9befe28c516d9323</cites><orcidid>0000-0001-7805-869X ; 0000-0003-2622-9017 ; 0000-0001-9505-7701</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30954620$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Ji Eun</creatorcontrib><creatorcontrib>Park, Joonyoung</creatorcontrib><creatorcontrib>Jun, Yearin</creatorcontrib><creatorcontrib>Oh, Yunseok</creatorcontrib><creatorcontrib>Ryoo, Gongmi</creatorcontrib><creatorcontrib>Jeong, Yoo-Seong</creatorcontrib><creatorcontrib>Gadalla, Hytham H</creatorcontrib><creatorcontrib>Min, Jee Sun</creatorcontrib><creatorcontrib>Jo, Jung Hwan</creatorcontrib><creatorcontrib>Song, Myung Geun</creatorcontrib><creatorcontrib>Kang, Keon Wook</creatorcontrib><creatorcontrib>Bae, Soo Kyung</creatorcontrib><creatorcontrib>Yeo, Yoon</creatorcontrib><creatorcontrib>Lee, Wooin</creatorcontrib><title>Expanding therapeutic utility of carfilzomib for breast cancer therapy by novel albumin-coated nanocrystal formulation</title><title>Journal of controlled release</title><addtitle>J Control Release</addtitle><description>Carfilzomib (CFZ) is the second-in-class proteasome inhibitor with much improved efficacy and safety profiles over bortezomib in multiple myeloma patients. 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Overall, our results demonstrate the potential of CFZ-alb NC as a viable formulation for breast cancer therapy.</description><subject>albumins</subject><subject>breast neoplasms</subject><subject>cytotoxicity</subject><subject>drugs</subject><subject>mice</subject><subject>myeloma</subject><subject>nanocrystals</subject><subject>neoplasm cells</subject><subject>patients</subject><subject>proteasome inhibitors</subject><subject>solubility</subject><subject>therapeutics</subject><issn>0168-3659</issn><issn>1873-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNqFkU9v1DAQxS0EotvCRwD5yCXBf2LHviChqkClSlzgbDnOpPXKsRfbWRE-PVl1qeDEZUaaee9pRj-E3lDSUkLl-327dylmCC0jVLekawmRz9COqp43ndbiOdptOtVwKfQFuixlTwgRvOtfogtOtOgkIzt0vPl5sHH08R7XB8j2AEv1Dm8l-LriNGFn8-TDrzT7AU8p4yGDLXUbRwf5bFrxsOKYjhCwDcMy-9i4ZCuMONqYXF5LteHknpdgq0_xFXox2VDg9blfoe-fbr5df2nuvn6-vf5417hO0dowAaOgwEate-VGpybNZEf1xDUB5UA6KSauiO5sT-2wrQeYgCknqBw1Z_wKfXjMPSzDDKODWLMN5pD9bPNqkvXm3030D-Y-HY2UXAnJt4B354CcfixQqpl9cRCCjZCWYhgTnMn-1P4vJaIjivVyk4pHqcuplAzT00WUmBNeszdnvOaE15DObHg339u_33ly_eHJfwNdWae7</recordid><startdate>20190528</startdate><enddate>20190528</enddate><creator>Park, Ji Eun</creator><creator>Park, Joonyoung</creator><creator>Jun, Yearin</creator><creator>Oh, Yunseok</creator><creator>Ryoo, Gongmi</creator><creator>Jeong, Yoo-Seong</creator><creator>Gadalla, Hytham H</creator><creator>Min, Jee Sun</creator><creator>Jo, Jung Hwan</creator><creator>Song, Myung Geun</creator><creator>Kang, Keon Wook</creator><creator>Bae, Soo Kyung</creator><creator>Yeo, Yoon</creator><creator>Lee, Wooin</creator><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7805-869X</orcidid><orcidid>https://orcid.org/0000-0003-2622-9017</orcidid><orcidid>https://orcid.org/0000-0001-9505-7701</orcidid></search><sort><creationdate>20190528</creationdate><title>Expanding therapeutic utility of carfilzomib for breast cancer therapy by novel albumin-coated nanocrystal formulation</title><author>Park, Ji Eun ; Park, Joonyoung ; Jun, Yearin ; Oh, Yunseok ; Ryoo, Gongmi ; Jeong, Yoo-Seong ; Gadalla, Hytham H ; Min, Jee Sun ; Jo, Jung Hwan ; Song, Myung Geun ; Kang, Keon Wook ; Bae, Soo Kyung ; Yeo, Yoon ; Lee, Wooin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c481t-25ed51e2d9978cdc8f926419f390e8ce6c65f38094a71ab8f9befe28c516d9323</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>albumins</topic><topic>breast neoplasms</topic><topic>cytotoxicity</topic><topic>drugs</topic><topic>mice</topic><topic>myeloma</topic><topic>nanocrystals</topic><topic>neoplasm cells</topic><topic>patients</topic><topic>proteasome inhibitors</topic><topic>solubility</topic><topic>therapeutics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Ji Eun</creatorcontrib><creatorcontrib>Park, Joonyoung</creatorcontrib><creatorcontrib>Jun, Yearin</creatorcontrib><creatorcontrib>Oh, Yunseok</creatorcontrib><creatorcontrib>Ryoo, Gongmi</creatorcontrib><creatorcontrib>Jeong, Yoo-Seong</creatorcontrib><creatorcontrib>Gadalla, Hytham H</creatorcontrib><creatorcontrib>Min, Jee Sun</creatorcontrib><creatorcontrib>Jo, Jung Hwan</creatorcontrib><creatorcontrib>Song, Myung Geun</creatorcontrib><creatorcontrib>Kang, Keon Wook</creatorcontrib><creatorcontrib>Bae, Soo Kyung</creatorcontrib><creatorcontrib>Yeo, Yoon</creatorcontrib><creatorcontrib>Lee, Wooin</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of controlled release</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Ji Eun</au><au>Park, Joonyoung</au><au>Jun, Yearin</au><au>Oh, Yunseok</au><au>Ryoo, Gongmi</au><au>Jeong, Yoo-Seong</au><au>Gadalla, Hytham H</au><au>Min, Jee Sun</au><au>Jo, Jung Hwan</au><au>Song, Myung Geun</au><au>Kang, Keon Wook</au><au>Bae, Soo Kyung</au><au>Yeo, Yoon</au><au>Lee, Wooin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expanding therapeutic utility of carfilzomib for breast cancer therapy by novel albumin-coated nanocrystal formulation</atitle><jtitle>Journal of controlled release</jtitle><addtitle>J Control Release</addtitle><date>2019-05-28</date><risdate>2019</risdate><volume>302</volume><spage>148</spage><epage>159</epage><pages>148-159</pages><issn>0168-3659</issn><eissn>1873-4995</eissn><abstract>Carfilzomib (CFZ) is the second-in-class proteasome inhibitor with much improved efficacy and safety profiles over bortezomib in multiple myeloma patients. In expanding the utility of CFZ to solid cancer therapy, the poor aqueous solubility and in vivo instability of CFZ are considered major drawbacks. We investigated whether a nanocrystal (NC) formulation can address these issues and enhance anticancer efficacy of CFZ against breast cancer. The surface of NC was coated with albumin in order to enhance the formulation stability and drug delivery to tumors via interactions with albumin-binding proteins located in and near cancer cells. The novel albumin-coated NC formulation of CFZ (CFZ-alb NC) displayed improved metabolic stability and enhanced cellular interactions, uptake and cytotoxic effects in breast cancer cells in vitro. Consistently, CFZ-alb NC showed greater anticancer efficacy in a murine 4T1 orthotopic breast cancer model than the currently used cyclodextrin-based formulation. 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| source | Elsevier ScienceDirect Journals Complete |
| subjects | albumins breast neoplasms cytotoxicity drugs mice myeloma nanocrystals neoplasm cells patients proteasome inhibitors solubility therapeutics |
| title | Expanding therapeutic utility of carfilzomib for breast cancer therapy by novel albumin-coated nanocrystal formulation |
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