Albumin-bound nanoparticle (nab) paclitaxel exhibits enhanced paclitaxel tissue distribution and tumor penetration
Purpose nab -paclitaxel demonstrates improved clinical efficacy compared with conventional Cremophor EL (CrEL)-paclitaxel in multiple tumor types. This study explored the distinctions in drug distribution between nab -paclitaxel and CrEL-paclitaxel and the underlying mechanisms. Methods Uptake and t...
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| Veröffentlicht in: | Cancer chemotherapy and pharmacology 2015-10, Vol.76 (4), p.699-712 |
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| creator | Chen, Nianhang Brachmann, Carrie Liu, Xiping Pierce, Daniel W. Dey, Joyoti Kerwin, William S. Li, Yan Zhou, Simon Hou, Shihe Carleton, Michael Klinghoffer, Richard A. Palmisano, Maria Chopra, Rajesh |
| description | Purpose
nab
-paclitaxel demonstrates improved clinical efficacy compared with conventional Cremophor EL (CrEL)-paclitaxel in multiple tumor types. This study explored the distinctions in drug distribution between
nab
-paclitaxel and CrEL-paclitaxel and the underlying mechanisms.
Methods
Uptake and transcytosis of paclitaxel were analyzed by vascular permeability assay across human endothelial cell monolayers. The tissue penetration of paclitaxel within tumors was evaluated by local injections into tumor xenografts and quantitative image analysis. The distribution profile of paclitaxel in solid-tumor patients was assessed using pharmacokinetic modeling and simulation.
Results
Live imaging demonstrated that albumin and paclitaxel were present in punctae in endothelial cells and could be observed in very close proximity, suggesting cotransport. Uptake and transport of albumin,
nab
-paclitaxel and paclitaxel were inhibited by clinically relevant CrEL concentrations. Further,
nab
-paclitaxel causes greater mitotic arrest in wider area within xenografted tumors than CrEL- or dimethyl sulfoxide-paclitaxel following local microinjection, demonstrating enhanced paclitaxel penetration and uptake by albumin within tumors. Modeling of paclitaxel distribution in patients with solid tumors indicated that
nab
-paclitaxel is more dependent upon transporter-mediated pathways for drug distribution into tissues than CrEL-paclitaxel. The percent dose delivered to tissue via transporter-mediated pathways is predicted to be constant with
nab
-paclitaxel but decrease with increasing CrEL-paclitaxel dose.
Conclusions
Compared with CrEL-paclitaxel,
nab
-paclitaxel demonstrated more efficient transport across endothelial cells, greater penetration and cytotoxic induction in xenograft tumors, and enhanced extravascular distribution in patients that are attributed to carrier-mediated transport. These observations are consistent with the distinct clinical efficacy and toxicity profile of
nab
-paclitaxel. |
| doi_str_mv | 10.1007/s00280-015-2833-5 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4768222</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3807752021</sourcerecordid><originalsourceid>FETCH-LOGICAL-c606t-ffae6f86c4dd79d7fbf341210fd4b2385e6dfe8c5de88a40abc0b694d877b9173</originalsourceid><addsrcrecordid>eNp1kUuLFDEUhYMoTtv6A9xIgRtdRPOspDfCMPiCATe6DnncTGeoTpVJSsZ_b5oeh3bhKpBz7rmH-yH0kpJ3lBD1vhLCNMGESsw051g-QhsqOMNEC_4YbQgXAktFxAV6VustIURQzp-iCzYyTndSblC5nNx6SBm7ec1hyDbPiy0t-QmGN9m6t8Ni_ZSavYNpgLt9cqnVAfLeZg_hXGyp1hWGkGorya0tzXmwPbKth7kMC2RoxR5_n6Mn0U4VXty_W_Tj08fvV1_w9bfPX68ur7EfydhwjBbGqEcvQlC7oKKLXFBGSQzCMa4ljCGC9jKA1lYQ6zxx404ErZTbUcW36MMpd1ndAYKH3AtMZinpYMtvM9tk_lVy2pub-ZcRatSMsR7w-j6gzD9XqM3czmvJvbOhijIhlejX3iJ6cvky11ogPmygxBwxmRMm0zGZIyYj-8yr82oPE3-5dAM7GWqX8g2Us9X_Tf0Deg2hzg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1712457414</pqid></control><display><type>article</type><title>Albumin-bound nanoparticle (nab) paclitaxel exhibits enhanced paclitaxel tissue distribution and tumor penetration</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Chen, Nianhang ; Brachmann, Carrie ; Liu, Xiping ; Pierce, Daniel W. ; Dey, Joyoti ; Kerwin, William S. ; Li, Yan ; Zhou, Simon ; Hou, Shihe ; Carleton, Michael ; Klinghoffer, Richard A. ; Palmisano, Maria ; Chopra, Rajesh</creator><creatorcontrib>Chen, Nianhang ; Brachmann, Carrie ; Liu, Xiping ; Pierce, Daniel W. ; Dey, Joyoti ; Kerwin, William S. ; Li, Yan ; Zhou, Simon ; Hou, Shihe ; Carleton, Michael ; Klinghoffer, Richard A. ; Palmisano, Maria ; Chopra, Rajesh</creatorcontrib><description>Purpose
nab
-paclitaxel demonstrates improved clinical efficacy compared with conventional Cremophor EL (CrEL)-paclitaxel in multiple tumor types. This study explored the distinctions in drug distribution between
nab
-paclitaxel and CrEL-paclitaxel and the underlying mechanisms.
Methods
Uptake and transcytosis of paclitaxel were analyzed by vascular permeability assay across human endothelial cell monolayers. The tissue penetration of paclitaxel within tumors was evaluated by local injections into tumor xenografts and quantitative image analysis. The distribution profile of paclitaxel in solid-tumor patients was assessed using pharmacokinetic modeling and simulation.
Results
Live imaging demonstrated that albumin and paclitaxel were present in punctae in endothelial cells and could be observed in very close proximity, suggesting cotransport. Uptake and transport of albumin,
nab
-paclitaxel and paclitaxel were inhibited by clinically relevant CrEL concentrations. Further,
nab
-paclitaxel causes greater mitotic arrest in wider area within xenografted tumors than CrEL- or dimethyl sulfoxide-paclitaxel following local microinjection, demonstrating enhanced paclitaxel penetration and uptake by albumin within tumors. Modeling of paclitaxel distribution in patients with solid tumors indicated that
nab
-paclitaxel is more dependent upon transporter-mediated pathways for drug distribution into tissues than CrEL-paclitaxel. The percent dose delivered to tissue via transporter-mediated pathways is predicted to be constant with
nab
-paclitaxel but decrease with increasing CrEL-paclitaxel dose.
Conclusions
Compared with CrEL-paclitaxel,
nab
-paclitaxel demonstrated more efficient transport across endothelial cells, greater penetration and cytotoxic induction in xenograft tumors, and enhanced extravascular distribution in patients that are attributed to carrier-mediated transport. These observations are consistent with the distinct clinical efficacy and toxicity profile of
nab
-paclitaxel.</description><identifier>ISSN: 0344-5704</identifier><identifier>EISSN: 1432-0843</identifier><identifier>DOI: 10.1007/s00280-015-2833-5</identifier><identifier>PMID: 26231955</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Animals ; Antineoplastic Agents, Phytogenic - administration & dosage ; Antineoplastic Agents, Phytogenic - metabolism ; Antineoplastic Agents, Phytogenic - pharmacokinetics ; Antineoplastic Agents, Phytogenic - therapeutic use ; Biological Transport - drug effects ; Cancer Research ; Capillary Permeability - drug effects ; Carcinoma - drug therapy ; Carcinoma - metabolism ; Carcinoma - pathology ; Cell Line, Tumor ; Cells, Cultured ; Drug Delivery Systems ; Endosomes - drug effects ; Endosomes - metabolism ; Endosomes - pathology ; Endothelium, Vascular - cytology ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - metabolism ; Endothelium, Vascular - pathology ; Human Umbilical Vein Endothelial Cells - cytology ; Human Umbilical Vein Endothelial Cells - drug effects ; Human Umbilical Vein Endothelial Cells - metabolism ; Humans ; Infusions, Intravenous ; Medicine ; Medicine & Public Health ; Mice, Nude ; Microinjections ; Nanoparticles - chemistry ; Oncology ; Original ; Original Article ; Paclitaxel - administration & dosage ; Paclitaxel - metabolism ; Paclitaxel - pharmacokinetics ; Paclitaxel - therapeutic use ; Pancreatic Neoplasms - drug therapy ; Pancreatic Neoplasms - metabolism ; Pancreatic Neoplasms - pathology ; Pharmacology/Toxicology ; Serum Albumin - chemistry ; Serum Albumin - metabolism ; Serum Albumin, Human ; Tissue Distribution ; Tubulin Modulators - administration & dosage ; Tubulin Modulators - metabolism ; Tubulin Modulators - pharmacokinetics ; Tubulin Modulators - therapeutic use ; Xenograft Model Antitumor Assays</subject><ispartof>Cancer chemotherapy and pharmacology, 2015-10, Vol.76 (4), p.699-712</ispartof><rights>The Author(s) 2015</rights><rights>Springer-Verlag Berlin Heidelberg 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c606t-ffae6f86c4dd79d7fbf341210fd4b2385e6dfe8c5de88a40abc0b694d877b9173</citedby><cites>FETCH-LOGICAL-c606t-ffae6f86c4dd79d7fbf341210fd4b2385e6dfe8c5de88a40abc0b694d877b9173</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/s00280-015-2833-5$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00280-015-2833-5$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26231955$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Nianhang</creatorcontrib><creatorcontrib>Brachmann, Carrie</creatorcontrib><creatorcontrib>Liu, Xiping</creatorcontrib><creatorcontrib>Pierce, Daniel W.</creatorcontrib><creatorcontrib>Dey, Joyoti</creatorcontrib><creatorcontrib>Kerwin, William S.</creatorcontrib><creatorcontrib>Li, Yan</creatorcontrib><creatorcontrib>Zhou, Simon</creatorcontrib><creatorcontrib>Hou, Shihe</creatorcontrib><creatorcontrib>Carleton, Michael</creatorcontrib><creatorcontrib>Klinghoffer, Richard A.</creatorcontrib><creatorcontrib>Palmisano, Maria</creatorcontrib><creatorcontrib>Chopra, Rajesh</creatorcontrib><title>Albumin-bound nanoparticle (nab) paclitaxel exhibits enhanced paclitaxel tissue distribution and tumor penetration</title><title>Cancer chemotherapy and pharmacology</title><addtitle>Cancer Chemother Pharmacol</addtitle><addtitle>Cancer Chemother Pharmacol</addtitle><description>Purpose
nab
-paclitaxel demonstrates improved clinical efficacy compared with conventional Cremophor EL (CrEL)-paclitaxel in multiple tumor types. This study explored the distinctions in drug distribution between
nab
-paclitaxel and CrEL-paclitaxel and the underlying mechanisms.
Methods
Uptake and transcytosis of paclitaxel were analyzed by vascular permeability assay across human endothelial cell monolayers. The tissue penetration of paclitaxel within tumors was evaluated by local injections into tumor xenografts and quantitative image analysis. The distribution profile of paclitaxel in solid-tumor patients was assessed using pharmacokinetic modeling and simulation.
Results
Live imaging demonstrated that albumin and paclitaxel were present in punctae in endothelial cells and could be observed in very close proximity, suggesting cotransport. Uptake and transport of albumin,
nab
-paclitaxel and paclitaxel were inhibited by clinically relevant CrEL concentrations. Further,
nab
-paclitaxel causes greater mitotic arrest in wider area within xenografted tumors than CrEL- or dimethyl sulfoxide-paclitaxel following local microinjection, demonstrating enhanced paclitaxel penetration and uptake by albumin within tumors. Modeling of paclitaxel distribution in patients with solid tumors indicated that
nab
-paclitaxel is more dependent upon transporter-mediated pathways for drug distribution into tissues than CrEL-paclitaxel. The percent dose delivered to tissue via transporter-mediated pathways is predicted to be constant with
nab
-paclitaxel but decrease with increasing CrEL-paclitaxel dose.
Conclusions
Compared with CrEL-paclitaxel,
nab
-paclitaxel demonstrated more efficient transport across endothelial cells, greater penetration and cytotoxic induction in xenograft tumors, and enhanced extravascular distribution in patients that are attributed to carrier-mediated transport. These observations are consistent with the distinct clinical efficacy and toxicity profile of
nab
-paclitaxel.</description><subject>Animals</subject><subject>Antineoplastic Agents, Phytogenic - administration & dosage</subject><subject>Antineoplastic Agents, Phytogenic - metabolism</subject><subject>Antineoplastic Agents, Phytogenic - pharmacokinetics</subject><subject>Antineoplastic Agents, Phytogenic - therapeutic use</subject><subject>Biological Transport - drug effects</subject><subject>Cancer Research</subject><subject>Capillary Permeability - drug effects</subject><subject>Carcinoma - drug therapy</subject><subject>Carcinoma - metabolism</subject><subject>Carcinoma - pathology</subject><subject>Cell Line, Tumor</subject><subject>Cells, Cultured</subject><subject>Drug Delivery Systems</subject><subject>Endosomes - drug effects</subject><subject>Endosomes - metabolism</subject><subject>Endosomes - pathology</subject><subject>Endothelium, Vascular - cytology</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Endothelium, Vascular - pathology</subject><subject>Human Umbilical Vein Endothelial Cells - cytology</subject><subject>Human Umbilical Vein Endothelial Cells - drug effects</subject><subject>Human Umbilical Vein Endothelial Cells - metabolism</subject><subject>Humans</subject><subject>Infusions, Intravenous</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice, Nude</subject><subject>Microinjections</subject><subject>Nanoparticles - chemistry</subject><subject>Oncology</subject><subject>Original</subject><subject>Original Article</subject><subject>Paclitaxel - administration & dosage</subject><subject>Paclitaxel - metabolism</subject><subject>Paclitaxel - pharmacokinetics</subject><subject>Paclitaxel - therapeutic use</subject><subject>Pancreatic Neoplasms - drug therapy</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Pharmacology/Toxicology</subject><subject>Serum Albumin - chemistry</subject><subject>Serum Albumin - metabolism</subject><subject>Serum Albumin, Human</subject><subject>Tissue Distribution</subject><subject>Tubulin Modulators - administration & dosage</subject><subject>Tubulin Modulators - metabolism</subject><subject>Tubulin Modulators - pharmacokinetics</subject><subject>Tubulin Modulators - therapeutic use</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0344-5704</issn><issn>1432-0843</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kUuLFDEUhYMoTtv6A9xIgRtdRPOspDfCMPiCATe6DnncTGeoTpVJSsZ_b5oeh3bhKpBz7rmH-yH0kpJ3lBD1vhLCNMGESsw051g-QhsqOMNEC_4YbQgXAktFxAV6VustIURQzp-iCzYyTndSblC5nNx6SBm7ec1hyDbPiy0t-QmGN9m6t8Ni_ZSavYNpgLt9cqnVAfLeZg_hXGyp1hWGkGorya0tzXmwPbKth7kMC2RoxR5_n6Mn0U4VXty_W_Tj08fvV1_w9bfPX68ur7EfydhwjBbGqEcvQlC7oKKLXFBGSQzCMa4ljCGC9jKA1lYQ6zxx404ErZTbUcW36MMpd1ndAYKH3AtMZinpYMtvM9tk_lVy2pub-ZcRatSMsR7w-j6gzD9XqM3czmvJvbOhijIhlejX3iJ6cvky11ogPmygxBwxmRMm0zGZIyYj-8yr82oPE3-5dAM7GWqX8g2Us9X_Tf0Deg2hzg</recordid><startdate>20151001</startdate><enddate>20151001</enddate><creator>Chen, Nianhang</creator><creator>Brachmann, Carrie</creator><creator>Liu, Xiping</creator><creator>Pierce, Daniel W.</creator><creator>Dey, Joyoti</creator><creator>Kerwin, William S.</creator><creator>Li, Yan</creator><creator>Zhou, Simon</creator><creator>Hou, Shihe</creator><creator>Carleton, Michael</creator><creator>Klinghoffer, Richard A.</creator><creator>Palmisano, Maria</creator><creator>Chopra, Rajesh</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</scope><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>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</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>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20151001</creationdate><title>Albumin-bound nanoparticle (nab) paclitaxel exhibits enhanced paclitaxel tissue distribution and tumor penetration</title><author>Chen, Nianhang ; Brachmann, Carrie ; Liu, Xiping ; Pierce, Daniel W. ; Dey, Joyoti ; Kerwin, William S. ; Li, Yan ; Zhou, Simon ; Hou, Shihe ; Carleton, Michael ; Klinghoffer, Richard A. ; Palmisano, Maria ; Chopra, Rajesh</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c606t-ffae6f86c4dd79d7fbf341210fd4b2385e6dfe8c5de88a40abc0b694d877b9173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Antineoplastic Agents, Phytogenic - administration & dosage</topic><topic>Antineoplastic Agents, Phytogenic - metabolism</topic><topic>Antineoplastic Agents, Phytogenic - pharmacokinetics</topic><topic>Antineoplastic Agents, Phytogenic - therapeutic use</topic><topic>Biological Transport - drug effects</topic><topic>Cancer Research</topic><topic>Capillary Permeability - drug effects</topic><topic>Carcinoma - drug therapy</topic><topic>Carcinoma - metabolism</topic><topic>Carcinoma - pathology</topic><topic>Cell Line, Tumor</topic><topic>Cells, Cultured</topic><topic>Drug Delivery Systems</topic><topic>Endosomes - drug effects</topic><topic>Endosomes - metabolism</topic><topic>Endosomes - pathology</topic><topic>Endothelium, Vascular - cytology</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Endothelium, Vascular - pathology</topic><topic>Human Umbilical Vein Endothelial Cells - cytology</topic><topic>Human Umbilical Vein Endothelial Cells - drug effects</topic><topic>Human Umbilical Vein Endothelial Cells - metabolism</topic><topic>Humans</topic><topic>Infusions, Intravenous</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mice, Nude</topic><topic>Microinjections</topic><topic>Nanoparticles - chemistry</topic><topic>Oncology</topic><topic>Original</topic><topic>Original Article</topic><topic>Paclitaxel - administration & dosage</topic><topic>Paclitaxel - metabolism</topic><topic>Paclitaxel - pharmacokinetics</topic><topic>Paclitaxel - therapeutic use</topic><topic>Pancreatic Neoplasms - drug therapy</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Pharmacology/Toxicology</topic><topic>Serum Albumin - chemistry</topic><topic>Serum Albumin - metabolism</topic><topic>Serum Albumin, Human</topic><topic>Tissue Distribution</topic><topic>Tubulin Modulators - administration & dosage</topic><topic>Tubulin Modulators - metabolism</topic><topic>Tubulin Modulators - pharmacokinetics</topic><topic>Tubulin Modulators - therapeutic use</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Nianhang</creatorcontrib><creatorcontrib>Brachmann, Carrie</creatorcontrib><creatorcontrib>Liu, Xiping</creatorcontrib><creatorcontrib>Pierce, Daniel W.</creatorcontrib><creatorcontrib>Dey, Joyoti</creatorcontrib><creatorcontrib>Kerwin, William S.</creatorcontrib><creatorcontrib>Li, Yan</creatorcontrib><creatorcontrib>Zhou, Simon</creatorcontrib><creatorcontrib>Hou, Shihe</creatorcontrib><creatorcontrib>Carleton, Michael</creatorcontrib><creatorcontrib>Klinghoffer, Richard A.</creatorcontrib><creatorcontrib>Palmisano, Maria</creatorcontrib><creatorcontrib>Chopra, Rajesh</creatorcontrib><collection>Springer Nature OA Free Journals</collection><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>Oncogenes and Growth Factors 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>Public Health Database</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>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</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>PubMed Central (Full Participant titles)</collection><jtitle>Cancer chemotherapy and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Nianhang</au><au>Brachmann, Carrie</au><au>Liu, Xiping</au><au>Pierce, Daniel W.</au><au>Dey, Joyoti</au><au>Kerwin, William S.</au><au>Li, Yan</au><au>Zhou, Simon</au><au>Hou, Shihe</au><au>Carleton, Michael</au><au>Klinghoffer, Richard A.</au><au>Palmisano, Maria</au><au>Chopra, Rajesh</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Albumin-bound nanoparticle (nab) paclitaxel exhibits enhanced paclitaxel tissue distribution and tumor penetration</atitle><jtitle>Cancer chemotherapy and pharmacology</jtitle><stitle>Cancer Chemother Pharmacol</stitle><addtitle>Cancer Chemother Pharmacol</addtitle><date>2015-10-01</date><risdate>2015</risdate><volume>76</volume><issue>4</issue><spage>699</spage><epage>712</epage><pages>699-712</pages><issn>0344-5704</issn><eissn>1432-0843</eissn><abstract>Purpose
nab
-paclitaxel demonstrates improved clinical efficacy compared with conventional Cremophor EL (CrEL)-paclitaxel in multiple tumor types. This study explored the distinctions in drug distribution between
nab
-paclitaxel and CrEL-paclitaxel and the underlying mechanisms.
Methods
Uptake and transcytosis of paclitaxel were analyzed by vascular permeability assay across human endothelial cell monolayers. The tissue penetration of paclitaxel within tumors was evaluated by local injections into tumor xenografts and quantitative image analysis. The distribution profile of paclitaxel in solid-tumor patients was assessed using pharmacokinetic modeling and simulation.
Results
Live imaging demonstrated that albumin and paclitaxel were present in punctae in endothelial cells and could be observed in very close proximity, suggesting cotransport. Uptake and transport of albumin,
nab
-paclitaxel and paclitaxel were inhibited by clinically relevant CrEL concentrations. Further,
nab
-paclitaxel causes greater mitotic arrest in wider area within xenografted tumors than CrEL- or dimethyl sulfoxide-paclitaxel following local microinjection, demonstrating enhanced paclitaxel penetration and uptake by albumin within tumors. Modeling of paclitaxel distribution in patients with solid tumors indicated that
nab
-paclitaxel is more dependent upon transporter-mediated pathways for drug distribution into tissues than CrEL-paclitaxel. The percent dose delivered to tissue via transporter-mediated pathways is predicted to be constant with
nab
-paclitaxel but decrease with increasing CrEL-paclitaxel dose.
Conclusions
Compared with CrEL-paclitaxel,
nab
-paclitaxel demonstrated more efficient transport across endothelial cells, greater penetration and cytotoxic induction in xenograft tumors, and enhanced extravascular distribution in patients that are attributed to carrier-mediated transport. These observations are consistent with the distinct clinical efficacy and toxicity profile of
nab
-paclitaxel.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>26231955</pmid><doi>10.1007/s00280-015-2833-5</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0344-5704 |
| ispartof | Cancer chemotherapy and pharmacology, 2015-10, Vol.76 (4), p.699-712 |
| issn | 0344-5704 1432-0843 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4768222 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Animals Antineoplastic Agents, Phytogenic - administration & dosage Antineoplastic Agents, Phytogenic - metabolism Antineoplastic Agents, Phytogenic - pharmacokinetics Antineoplastic Agents, Phytogenic - therapeutic use Biological Transport - drug effects Cancer Research Capillary Permeability - drug effects Carcinoma - drug therapy Carcinoma - metabolism Carcinoma - pathology Cell Line, Tumor Cells, Cultured Drug Delivery Systems Endosomes - drug effects Endosomes - metabolism Endosomes - pathology Endothelium, Vascular - cytology Endothelium, Vascular - drug effects Endothelium, Vascular - metabolism Endothelium, Vascular - pathology Human Umbilical Vein Endothelial Cells - cytology Human Umbilical Vein Endothelial Cells - drug effects Human Umbilical Vein Endothelial Cells - metabolism Humans Infusions, Intravenous Medicine Medicine & Public Health Mice, Nude Microinjections Nanoparticles - chemistry Oncology Original Original Article Paclitaxel - administration & dosage Paclitaxel - metabolism Paclitaxel - pharmacokinetics Paclitaxel - therapeutic use Pancreatic Neoplasms - drug therapy Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - pathology Pharmacology/Toxicology Serum Albumin - chemistry Serum Albumin - metabolism Serum Albumin, Human Tissue Distribution Tubulin Modulators - administration & dosage Tubulin Modulators - metabolism Tubulin Modulators - pharmacokinetics Tubulin Modulators - therapeutic use Xenograft Model Antitumor Assays |
| title | Albumin-bound nanoparticle (nab) paclitaxel exhibits enhanced paclitaxel tissue distribution and tumor penetration |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T19%3A58%3A34IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Albumin-bound%20nanoparticle%20(nab)%20paclitaxel%20exhibits%20enhanced%20paclitaxel%20tissue%20distribution%20and%20tumor%20penetration&rft.jtitle=Cancer%20chemotherapy%20and%20pharmacology&rft.au=Chen,%20Nianhang&rft.date=2015-10-01&rft.volume=76&rft.issue=4&rft.spage=699&rft.epage=712&rft.pages=699-712&rft.issn=0344-5704&rft.eissn=1432-0843&rft_id=info:doi/10.1007/s00280-015-2833-5&rft_dat=%3Cproquest_pubme%3E3807752021%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1712457414&rft_id=info:pmid/26231955&rfr_iscdi=true |