Combined Microdialysis-Tumor Homogenate Method for the Study of the Steady State Compartmental Distribution of a Hydrophobic Anticancer Drug in Patient-Derived Xenografts
Purpose To develop a reproducible microdialysis-tumor homogenate method for the study of the intratumor distribution of a highly hydrophobic anticancer drug (SN-38; 7-ethyl-10-hydroxycamptothecin) in neuroblastoma patient-derived xenografts. Methods We studied the nonspecific binding of SN-38 to the...
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| Veröffentlicht in: | Pharmaceutical research 2015-09, Vol.32 (9), p.2889-2900 |
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| creator | Monterrubio, Carles Paco, Sonia Vila-Ubach, Monica Rodríguez, Eva Glisoni, Romina Lavarino, Cinzia Schaiquevich, Paula Sosnik, Alejandro Mora, Jaume Carcaboso, Angel M. |
| description | Purpose
To develop a reproducible microdialysis-tumor homogenate method for the study of the intratumor distribution of a highly hydrophobic anticancer drug (SN-38; 7-ethyl-10-hydroxycamptothecin) in neuroblastoma patient-derived xenografts.
Methods
We studied the nonspecific binding of SN-38 to the microdialysis tubing in the presence of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) in the perfusate. We calibrated the microdialysis probes by the zero flow rate (ZFR) method and calculated the enhancement factor (
f
= extrapolated SN-38 concentration at the ZFR / SN-38 concentration in the dialysed solution) of HPBCD. We characterized the extravasation of HPBCD to tumors engrafted in mice.
In vivo
microdialysis and terminal homogenate data at the steady state (subcutaneous pump infusions) were used to calculate the volume of distribution of unbound SN-38 (V
u,tumor
) in neuroblastoma.
Results
HPBCD (10%
w/v
) in the perfusate prevented the nonspecific binding of SN-38 to the microdialysis probe and enhanced SN-38 recovery (
f
= 1.86). The extravasation of HPBCD in the tumor during microdialysis was lower than 1%. V
u,tumor
values were above 3 mL/g tumor for both neuroblastoma models and suggested efficient cellular penetration of SN-38.
Conclusions
The method contributes to overcome the limitations of the microdialysis technique in hydrophobic drugs and provides a powerful tool to characterize compartmental anticancer drug distribution in xenografts. |
| doi_str_mv | 10.1007/s11095-015-1671-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1717501693</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1717501693</sourcerecordid><originalsourceid>FETCH-LOGICAL-c430t-1ded4cb837309a2a7d8683fb7d802553839cff3ed33b0bec5b5b486d18e9351c3</originalsourceid><addsrcrecordid>eNqNkdGK1DAUhoso7rj6AN5IwBtvojlN0zSXy4w6wi4Ku8LelbQ5ncnSJmOSCvNKPqUpM4oIgleHk3znPwlfUbwE9hYYk-8iAFOCMhAUaglUPSpWICSnilX3j4sVk2VFG1nBRfEsxgfGWAOqelpclEJKLku-Kn6s_dRZh4bc2D54Y_V4jDbSu3nygWz95HfodEJyg2nvDRnyadojuU2zORI_nBvUubtNC5gDDzqkCV3SI9nYmILt5mS9W3BNtkcT_GHvO9uTK5dsr12PgWzCvCPWkS862TxKNxjs9_yse3R-F_SQ4vPiyaDHiC_O9bL4-uH93XpLrz9__LS-uqZ9xVmiYNBUfddwyZnSpZamqRs-dLmyUgjecNUPA0fDecc67EUnuqqpDTSouICeXxZvTrmH4L_NGFM72djjOGqHfo4tSJCCQa34f6CsrCslapHR13-hD34OLn9koaARVQUqU3CisosYAw7tIdhJh2MLrF2ctyfnbXbeLs7bZebVOXnuJjS_J35JzkB5AmK-cjsMf6z-Z-pPcQW5MQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1701854419</pqid></control><display><type>article</type><title>Combined Microdialysis-Tumor Homogenate Method for the Study of the Steady State Compartmental Distribution of a Hydrophobic Anticancer Drug in Patient-Derived Xenografts</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Monterrubio, Carles ; Paco, Sonia ; Vila-Ubach, Monica ; Rodríguez, Eva ; Glisoni, Romina ; Lavarino, Cinzia ; Schaiquevich, Paula ; Sosnik, Alejandro ; Mora, Jaume ; Carcaboso, Angel M.</creator><creatorcontrib>Monterrubio, Carles ; Paco, Sonia ; Vila-Ubach, Monica ; Rodríguez, Eva ; Glisoni, Romina ; Lavarino, Cinzia ; Schaiquevich, Paula ; Sosnik, Alejandro ; Mora, Jaume ; Carcaboso, Angel M.</creatorcontrib><description>Purpose
To develop a reproducible microdialysis-tumor homogenate method for the study of the intratumor distribution of a highly hydrophobic anticancer drug (SN-38; 7-ethyl-10-hydroxycamptothecin) in neuroblastoma patient-derived xenografts.
Methods
We studied the nonspecific binding of SN-38 to the microdialysis tubing in the presence of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) in the perfusate. We calibrated the microdialysis probes by the zero flow rate (ZFR) method and calculated the enhancement factor (
f
= extrapolated SN-38 concentration at the ZFR / SN-38 concentration in the dialysed solution) of HPBCD. We characterized the extravasation of HPBCD to tumors engrafted in mice.
In vivo
microdialysis and terminal homogenate data at the steady state (subcutaneous pump infusions) were used to calculate the volume of distribution of unbound SN-38 (V
u,tumor
) in neuroblastoma.
Results
HPBCD (10%
w/v
) in the perfusate prevented the nonspecific binding of SN-38 to the microdialysis probe and enhanced SN-38 recovery (
f
= 1.86). The extravasation of HPBCD in the tumor during microdialysis was lower than 1%. V
u,tumor
values were above 3 mL/g tumor for both neuroblastoma models and suggested efficient cellular penetration of SN-38.
Conclusions
The method contributes to overcome the limitations of the microdialysis technique in hydrophobic drugs and provides a powerful tool to characterize compartmental anticancer drug distribution in xenografts.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1007/s11095-015-1671-9</identifier><identifier>PMID: 25773723</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>2-Hydroxypropyl-beta-cyclodextrin ; Animals ; Antineoplastic Agents - metabolism ; Antineoplastic Agents - pharmacology ; beta-Cyclodextrins - metabolism ; beta-Cyclodextrins - pharmacology ; Biochemistry ; Biomedical and Life Sciences ; Biomedical Engineering and Bioengineering ; Biomedicine ; Camptothecin - analogs & derivatives ; Camptothecin - metabolism ; Camptothecin - pharmacology ; Chemotherapy ; Children & youth ; Heterografts - metabolism ; Humans ; Hydrophobic and Hydrophilic Interactions ; Medical Law ; Mice ; Mice, Nude ; Microdialysis - methods ; Neuroblastoma - drug therapy ; Neuroblastoma - metabolism ; Pharmacology ; Pharmacology/Toxicology ; Pharmacy ; Research Paper ; Tumors</subject><ispartof>Pharmaceutical research, 2015-09, Vol.32 (9), p.2889-2900</ispartof><rights>Springer Science+Business Media New York 2015</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c430t-1ded4cb837309a2a7d8683fb7d802553839cff3ed33b0bec5b5b486d18e9351c3</citedby><cites>FETCH-LOGICAL-c430t-1ded4cb837309a2a7d8683fb7d802553839cff3ed33b0bec5b5b486d18e9351c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11095-015-1671-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11095-015-1671-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25773723$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Monterrubio, Carles</creatorcontrib><creatorcontrib>Paco, Sonia</creatorcontrib><creatorcontrib>Vila-Ubach, Monica</creatorcontrib><creatorcontrib>Rodríguez, Eva</creatorcontrib><creatorcontrib>Glisoni, Romina</creatorcontrib><creatorcontrib>Lavarino, Cinzia</creatorcontrib><creatorcontrib>Schaiquevich, Paula</creatorcontrib><creatorcontrib>Sosnik, Alejandro</creatorcontrib><creatorcontrib>Mora, Jaume</creatorcontrib><creatorcontrib>Carcaboso, Angel M.</creatorcontrib><title>Combined Microdialysis-Tumor Homogenate Method for the Study of the Steady State Compartmental Distribution of a Hydrophobic Anticancer Drug in Patient-Derived Xenografts</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><addtitle>Pharm Res</addtitle><description>Purpose
To develop a reproducible microdialysis-tumor homogenate method for the study of the intratumor distribution of a highly hydrophobic anticancer drug (SN-38; 7-ethyl-10-hydroxycamptothecin) in neuroblastoma patient-derived xenografts.
Methods
We studied the nonspecific binding of SN-38 to the microdialysis tubing in the presence of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) in the perfusate. We calibrated the microdialysis probes by the zero flow rate (ZFR) method and calculated the enhancement factor (
f
= extrapolated SN-38 concentration at the ZFR / SN-38 concentration in the dialysed solution) of HPBCD. We characterized the extravasation of HPBCD to tumors engrafted in mice.
In vivo
microdialysis and terminal homogenate data at the steady state (subcutaneous pump infusions) were used to calculate the volume of distribution of unbound SN-38 (V
u,tumor
) in neuroblastoma.
Results
HPBCD (10%
w/v
) in the perfusate prevented the nonspecific binding of SN-38 to the microdialysis probe and enhanced SN-38 recovery (
f
= 1.86). The extravasation of HPBCD in the tumor during microdialysis was lower than 1%. V
u,tumor
values were above 3 mL/g tumor for both neuroblastoma models and suggested efficient cellular penetration of SN-38.
Conclusions
The method contributes to overcome the limitations of the microdialysis technique in hydrophobic drugs and provides a powerful tool to characterize compartmental anticancer drug distribution in xenografts.</description><subject>2-Hydroxypropyl-beta-cyclodextrin</subject><subject>Animals</subject><subject>Antineoplastic Agents - metabolism</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>beta-Cyclodextrins - metabolism</subject><subject>beta-Cyclodextrins - pharmacology</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering and Bioengineering</subject><subject>Biomedicine</subject><subject>Camptothecin - analogs & derivatives</subject><subject>Camptothecin - metabolism</subject><subject>Camptothecin - pharmacology</subject><subject>Chemotherapy</subject><subject>Children & youth</subject><subject>Heterografts - metabolism</subject><subject>Humans</subject><subject>Hydrophobic and Hydrophilic Interactions</subject><subject>Medical Law</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Microdialysis - methods</subject><subject>Neuroblastoma - drug therapy</subject><subject>Neuroblastoma - metabolism</subject><subject>Pharmacology</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacy</subject><subject>Research Paper</subject><subject>Tumors</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqNkdGK1DAUhoso7rj6AN5IwBtvojlN0zSXy4w6wi4Ku8LelbQ5ncnSJmOSCvNKPqUpM4oIgleHk3znPwlfUbwE9hYYk-8iAFOCMhAUaglUPSpWICSnilX3j4sVk2VFG1nBRfEsxgfGWAOqelpclEJKLku-Kn6s_dRZh4bc2D54Y_V4jDbSu3nygWz95HfodEJyg2nvDRnyadojuU2zORI_nBvUubtNC5gDDzqkCV3SI9nYmILt5mS9W3BNtkcT_GHvO9uTK5dsr12PgWzCvCPWkS862TxKNxjs9_yse3R-F_SQ4vPiyaDHiC_O9bL4-uH93XpLrz9__LS-uqZ9xVmiYNBUfddwyZnSpZamqRs-dLmyUgjecNUPA0fDecc67EUnuqqpDTSouICeXxZvTrmH4L_NGFM72djjOGqHfo4tSJCCQa34f6CsrCslapHR13-hD34OLn9koaARVQUqU3CisosYAw7tIdhJh2MLrF2ctyfnbXbeLs7bZebVOXnuJjS_J35JzkB5AmK-cjsMf6z-Z-pPcQW5MQ</recordid><startdate>20150901</startdate><enddate>20150901</enddate><creator>Monterrubio, Carles</creator><creator>Paco, Sonia</creator><creator>Vila-Ubach, Monica</creator><creator>Rodríguez, Eva</creator><creator>Glisoni, Romina</creator><creator>Lavarino, Cinzia</creator><creator>Schaiquevich, Paula</creator><creator>Sosnik, Alejandro</creator><creator>Mora, Jaume</creator><creator>Carcaboso, Angel M.</creator><general>Springer US</general><general>Springer Nature B.V</general><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>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20150901</creationdate><title>Combined Microdialysis-Tumor Homogenate Method for the Study of the Steady State Compartmental Distribution of a Hydrophobic Anticancer Drug in Patient-Derived Xenografts</title><author>Monterrubio, Carles ; Paco, Sonia ; Vila-Ubach, Monica ; Rodríguez, Eva ; Glisoni, Romina ; Lavarino, Cinzia ; Schaiquevich, Paula ; Sosnik, Alejandro ; Mora, Jaume ; Carcaboso, Angel M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c430t-1ded4cb837309a2a7d8683fb7d802553839cff3ed33b0bec5b5b486d18e9351c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>2-Hydroxypropyl-beta-cyclodextrin</topic><topic>Animals</topic><topic>Antineoplastic Agents - metabolism</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>beta-Cyclodextrins - metabolism</topic><topic>beta-Cyclodextrins - pharmacology</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical Engineering and Bioengineering</topic><topic>Biomedicine</topic><topic>Camptothecin - analogs & derivatives</topic><topic>Camptothecin - metabolism</topic><topic>Camptothecin - pharmacology</topic><topic>Chemotherapy</topic><topic>Children & youth</topic><topic>Heterografts - metabolism</topic><topic>Humans</topic><topic>Hydrophobic and Hydrophilic Interactions</topic><topic>Medical Law</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Microdialysis - methods</topic><topic>Neuroblastoma - drug therapy</topic><topic>Neuroblastoma - metabolism</topic><topic>Pharmacology</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacy</topic><topic>Research Paper</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Monterrubio, Carles</creatorcontrib><creatorcontrib>Paco, Sonia</creatorcontrib><creatorcontrib>Vila-Ubach, Monica</creatorcontrib><creatorcontrib>Rodríguez, Eva</creatorcontrib><creatorcontrib>Glisoni, Romina</creatorcontrib><creatorcontrib>Lavarino, Cinzia</creatorcontrib><creatorcontrib>Schaiquevich, Paula</creatorcontrib><creatorcontrib>Sosnik, Alejandro</creatorcontrib><creatorcontrib>Mora, Jaume</creatorcontrib><creatorcontrib>Carcaboso, Angel M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Monterrubio, Carles</au><au>Paco, Sonia</au><au>Vila-Ubach, Monica</au><au>Rodríguez, Eva</au><au>Glisoni, Romina</au><au>Lavarino, Cinzia</au><au>Schaiquevich, Paula</au><au>Sosnik, Alejandro</au><au>Mora, Jaume</au><au>Carcaboso, Angel M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Combined Microdialysis-Tumor Homogenate Method for the Study of the Steady State Compartmental Distribution of a Hydrophobic Anticancer Drug in Patient-Derived Xenografts</atitle><jtitle>Pharmaceutical research</jtitle><stitle>Pharm Res</stitle><addtitle>Pharm Res</addtitle><date>2015-09-01</date><risdate>2015</risdate><volume>32</volume><issue>9</issue><spage>2889</spage><epage>2900</epage><pages>2889-2900</pages><issn>0724-8741</issn><eissn>1573-904X</eissn><abstract>Purpose
To develop a reproducible microdialysis-tumor homogenate method for the study of the intratumor distribution of a highly hydrophobic anticancer drug (SN-38; 7-ethyl-10-hydroxycamptothecin) in neuroblastoma patient-derived xenografts.
Methods
We studied the nonspecific binding of SN-38 to the microdialysis tubing in the presence of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) in the perfusate. We calibrated the microdialysis probes by the zero flow rate (ZFR) method and calculated the enhancement factor (
f
= extrapolated SN-38 concentration at the ZFR / SN-38 concentration in the dialysed solution) of HPBCD. We characterized the extravasation of HPBCD to tumors engrafted in mice.
In vivo
microdialysis and terminal homogenate data at the steady state (subcutaneous pump infusions) were used to calculate the volume of distribution of unbound SN-38 (V
u,tumor
) in neuroblastoma.
Results
HPBCD (10%
w/v
) in the perfusate prevented the nonspecific binding of SN-38 to the microdialysis probe and enhanced SN-38 recovery (
f
= 1.86). The extravasation of HPBCD in the tumor during microdialysis was lower than 1%. V
u,tumor
values were above 3 mL/g tumor for both neuroblastoma models and suggested efficient cellular penetration of SN-38.
Conclusions
The method contributes to overcome the limitations of the microdialysis technique in hydrophobic drugs and provides a powerful tool to characterize compartmental anticancer drug distribution in xenografts.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>25773723</pmid><doi>10.1007/s11095-015-1671-9</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0724-8741 |
| ispartof | Pharmaceutical research, 2015-09, Vol.32 (9), p.2889-2900 |
| issn | 0724-8741 1573-904X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1717501693 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | 2-Hydroxypropyl-beta-cyclodextrin Animals Antineoplastic Agents - metabolism Antineoplastic Agents - pharmacology beta-Cyclodextrins - metabolism beta-Cyclodextrins - pharmacology Biochemistry Biomedical and Life Sciences Biomedical Engineering and Bioengineering Biomedicine Camptothecin - analogs & derivatives Camptothecin - metabolism Camptothecin - pharmacology Chemotherapy Children & youth Heterografts - metabolism Humans Hydrophobic and Hydrophilic Interactions Medical Law Mice Mice, Nude Microdialysis - methods Neuroblastoma - drug therapy Neuroblastoma - metabolism Pharmacology Pharmacology/Toxicology Pharmacy Research Paper Tumors |
| title | Combined Microdialysis-Tumor Homogenate Method for the Study of the Steady State Compartmental Distribution of a Hydrophobic Anticancer Drug in Patient-Derived Xenografts |
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