A reanalysis of nanoparticle tumor delivery using classical pharmacokinetic metrics
Nanoparticle (NP) delivery to solid tumors has recently been questioned. To better understand the magnitude of NP tumor delivery, we reanalyzed published murine NP tumor pharmacokinetic (PK) data used in the Wilhelm . study. Studies included in their analysis reporting matched tumor and blood concen...
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| Veröffentlicht in: | Science advances 2020-07, Vol.6 (29), p.eaay9249-eaay9249 |
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| creator | Price, Lauren S L Stern, Stephan T Deal, Allison M Kabanov, Alexander V Zamboni, William C |
| description | Nanoparticle (NP) delivery to solid tumors has recently been questioned. To better understand the magnitude of NP tumor delivery, we reanalyzed published murine NP tumor pharmacokinetic (PK) data used in the Wilhelm
. study. Studies included in their analysis reporting matched tumor and blood concentration versus time data were evaluated using classical PK endpoints and compared to the unestablished percent injected dose (%ID) in tumor metric from the Wilhelm
. study. The %ID in tumor was poorly correlated with standard PK metrics that describe NP tumor delivery (AUC
/AUC
ratio) and only moderately associated with maximal tumor concentration. The relative tumor delivery of NPs was ~100-fold greater as assessed by the standard AUC
/AUC
ratio than by %ID in tumor. These results strongly suggest that PK metrics and calculations can influence the interpretation of NP tumor delivery and stress the need to properly validate novel PK metrics against traditional approaches. |
| doi_str_mv | 10.1126/sciadv.aay9249 |
| format | Article |
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. study. Studies included in their analysis reporting matched tumor and blood concentration versus time data were evaluated using classical PK endpoints and compared to the unestablished percent injected dose (%ID) in tumor metric from the Wilhelm
. study. The %ID in tumor was poorly correlated with standard PK metrics that describe NP tumor delivery (AUC
/AUC
ratio) and only moderately associated with maximal tumor concentration. The relative tumor delivery of NPs was ~100-fold greater as assessed by the standard AUC
/AUC
ratio than by %ID in tumor. These results strongly suggest that PK metrics and calculations can influence the interpretation of NP tumor delivery and stress the need to properly validate novel PK metrics against traditional approaches.</description><identifier>ISSN: 2375-2548</identifier><identifier>EISSN: 2375-2548</identifier><identifier>DOI: 10.1126/sciadv.aay9249</identifier><identifier>PMID: 32832614</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Cancer ; Materials Science ; SciAdv r-articles</subject><ispartof>Science advances, 2020-07, Vol.6 (29), p.eaay9249-eaay9249</ispartof><rights>Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).</rights><rights>Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). 2020 The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-8971a79b48e9b5441f888e9af911981cdd7ff45e40e4a68f645d136134c6fc403</citedby><cites>FETCH-LOGICAL-c456t-8971a79b48e9b5441f888e9af911981cdd7ff45e40e4a68f645d136134c6fc403</cites><orcidid>0000-0001-7810-0499 ; 0000-0003-1150-7598 ; 0000-0002-8319-4482 ; 0000-0002-3665-946X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439617/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439617/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32832614$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Price, Lauren S L</creatorcontrib><creatorcontrib>Stern, Stephan T</creatorcontrib><creatorcontrib>Deal, Allison M</creatorcontrib><creatorcontrib>Kabanov, Alexander V</creatorcontrib><creatorcontrib>Zamboni, William C</creatorcontrib><title>A reanalysis of nanoparticle tumor delivery using classical pharmacokinetic metrics</title><title>Science advances</title><addtitle>Sci Adv</addtitle><description>Nanoparticle (NP) delivery to solid tumors has recently been questioned. To better understand the magnitude of NP tumor delivery, we reanalyzed published murine NP tumor pharmacokinetic (PK) data used in the Wilhelm
. study. Studies included in their analysis reporting matched tumor and blood concentration versus time data were evaluated using classical PK endpoints and compared to the unestablished percent injected dose (%ID) in tumor metric from the Wilhelm
. study. The %ID in tumor was poorly correlated with standard PK metrics that describe NP tumor delivery (AUC
/AUC
ratio) and only moderately associated with maximal tumor concentration. The relative tumor delivery of NPs was ~100-fold greater as assessed by the standard AUC
/AUC
ratio than by %ID in tumor. These results strongly suggest that PK metrics and calculations can influence the interpretation of NP tumor delivery and stress the need to properly validate novel PK metrics against traditional approaches.</description><subject>Cancer</subject><subject>Materials Science</subject><subject>SciAdv r-articles</subject><issn>2375-2548</issn><issn>2375-2548</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNpVUU1LAzEUDKLYUnv1KDl6ad1sstnkIpTiFxQ8qOfwmk3aaHZTk91C_70rraWe3sCbmTe8QeiaZFNCcn6XtINqOwXYyZzJMzTMaVlM8oKJ8xM8QOOUPrMsI4zzgshLNKC5oDknbIjeZjgaaMDvkks4WNxAEzYQW6e9wW1Xh4gr493WxB3ukmtWWHtIyWnweLOGWIMOX64xvQDXpo1Opyt0YcEnMz7MEfp4fHifP08Wr08v89liolnB24mQJYFSLpkwclkwRqwQPQQrCZGC6KoqrWWFYZlhwIXlrKgI5YQyza1mGR2h-73vplvWptKmaSN4tYmuhrhTAZz6v2ncWq3CVpWMSk7K3uD2YBDDd2dSq2qXtPEeGhO6pHJGuSh50fNHaLqn6hhSisYez5BM_Zah9mWoQxm94OY03JH-93r6A2fIicQ</recordid><startdate>20200701</startdate><enddate>20200701</enddate><creator>Price, Lauren S L</creator><creator>Stern, Stephan T</creator><creator>Deal, Allison M</creator><creator>Kabanov, Alexander V</creator><creator>Zamboni, William C</creator><general>American Association for the Advancement of Science</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7810-0499</orcidid><orcidid>https://orcid.org/0000-0003-1150-7598</orcidid><orcidid>https://orcid.org/0000-0002-8319-4482</orcidid><orcidid>https://orcid.org/0000-0002-3665-946X</orcidid></search><sort><creationdate>20200701</creationdate><title>A reanalysis of nanoparticle tumor delivery using classical pharmacokinetic metrics</title><author>Price, Lauren S L ; Stern, Stephan T ; Deal, Allison M ; Kabanov, Alexander V ; Zamboni, William C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-8971a79b48e9b5441f888e9af911981cdd7ff45e40e4a68f645d136134c6fc403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Cancer</topic><topic>Materials Science</topic><topic>SciAdv r-articles</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Price, Lauren S L</creatorcontrib><creatorcontrib>Stern, Stephan T</creatorcontrib><creatorcontrib>Deal, Allison M</creatorcontrib><creatorcontrib>Kabanov, Alexander V</creatorcontrib><creatorcontrib>Zamboni, William C</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Science advances</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Price, Lauren S L</au><au>Stern, Stephan T</au><au>Deal, Allison M</au><au>Kabanov, Alexander V</au><au>Zamboni, William C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A reanalysis of nanoparticle tumor delivery using classical pharmacokinetic metrics</atitle><jtitle>Science advances</jtitle><addtitle>Sci Adv</addtitle><date>2020-07-01</date><risdate>2020</risdate><volume>6</volume><issue>29</issue><spage>eaay9249</spage><epage>eaay9249</epage><pages>eaay9249-eaay9249</pages><issn>2375-2548</issn><eissn>2375-2548</eissn><abstract>Nanoparticle (NP) delivery to solid tumors has recently been questioned. To better understand the magnitude of NP tumor delivery, we reanalyzed published murine NP tumor pharmacokinetic (PK) data used in the Wilhelm
. study. Studies included in their analysis reporting matched tumor and blood concentration versus time data were evaluated using classical PK endpoints and compared to the unestablished percent injected dose (%ID) in tumor metric from the Wilhelm
. study. The %ID in tumor was poorly correlated with standard PK metrics that describe NP tumor delivery (AUC
/AUC
ratio) and only moderately associated with maximal tumor concentration. The relative tumor delivery of NPs was ~100-fold greater as assessed by the standard AUC
/AUC
ratio than by %ID in tumor. These results strongly suggest that PK metrics and calculations can influence the interpretation of NP tumor delivery and stress the need to properly validate novel PK metrics against traditional approaches.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>32832614</pmid><doi>10.1126/sciadv.aay9249</doi><orcidid>https://orcid.org/0000-0001-7810-0499</orcidid><orcidid>https://orcid.org/0000-0003-1150-7598</orcidid><orcidid>https://orcid.org/0000-0002-8319-4482</orcidid><orcidid>https://orcid.org/0000-0002-3665-946X</orcidid><oa>free_for_read</oa></addata></record> |
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| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Cancer Materials Science SciAdv r-articles |
| title | A reanalysis of nanoparticle tumor delivery using classical pharmacokinetic metrics |
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