Distribution of Doxorubicin in Rats Undergoing Ultrasonic Drug Delivery
Ultrasound (US) increases efficacy of drugs delivered from micelles, but the pharmacokinetics have not been studied previously. In this study, US was used to deliver doxorubicin (Dox) sequestered in micelles in an in vivo rat model with bilateral leg tumors. One of two frequencies with identical mec...
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| Veröffentlicht in: | Journal of pharmaceutical sciences 2010-07, Vol.99 (7), p.3122-3131 |
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| creator | Staples, Bryant J. Pitt, William G. Roeder, Beverly L. Husseini, Ghaleb A. Rajeev, Deepthi Bruce Schaalje, G. |
| description | Ultrasound (US) increases efficacy of drugs delivered from micelles, but the pharmacokinetics have not been studied previously. In this study, US was used to deliver doxorubicin (Dox) sequestered in micelles in an in vivo rat model with bilateral leg tumors. One of two frequencies with identical mechanical index and intensity was delivered for 15min to one tumor immediately after systemic injection of micellar Dox. Pharmacokinetics in myocardium, liver, skeletal muscle, and tumors were measured for 1 week. When applied in combination with micellar Dox, the ultrasoincated tumor had higher Dox concentrations at 30min, compared to bilateral noninsonated controls. Initially, concentrations were highest in heart and liver, but within 24h they decreased significantly. From 24h to 7 days, concentrations remained highest in tumors, regardless of whether they received US or not. Comparison of insonated and noninsonated tumors showed 50% more Dox in the insonated tumor at 30min posttreatment. Four weekly treatment produced additional Dox accumulation in the myocardium but not in liver, skeletal leg muscle, or tumors compared to single treatment. Controls showed that neither US nor the empty carrier impacted tumor growth. This study shows that US causes more release of drug at the targeted tumor. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3122–3131, 2010 |
| doi_str_mv | 10.1002/jps.22088 |
| format | Article |
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In this study, US was used to deliver doxorubicin (Dox) sequestered in micelles in an in vivo rat model with bilateral leg tumors. One of two frequencies with identical mechanical index and intensity was delivered for 15min to one tumor immediately after systemic injection of micellar Dox. Pharmacokinetics in myocardium, liver, skeletal muscle, and tumors were measured for 1 week. When applied in combination with micellar Dox, the ultrasoincated tumor had higher Dox concentrations at 30min, compared to bilateral noninsonated controls. Initially, concentrations were highest in heart and liver, but within 24h they decreased significantly. From 24h to 7 days, concentrations remained highest in tumors, regardless of whether they received US or not. Comparison of insonated and noninsonated tumors showed 50% more Dox in the insonated tumor at 30min posttreatment. Four weekly treatment produced additional Dox accumulation in the myocardium but not in liver, skeletal leg muscle, or tumors compared to single treatment. Controls showed that neither US nor the empty carrier impacted tumor growth. This study shows that US causes more release of drug at the targeted tumor. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3122–3131, 2010</description><identifier>ISSN: 0022-3549</identifier><identifier>ISSN: 1520-6017</identifier><identifier>EISSN: 1520-6017</identifier><identifier>DOI: 10.1002/jps.22088</identifier><identifier>PMID: 20166203</identifier><identifier>CODEN: JPMSAE</identifier><language>eng</language><publisher>Hoboken: Elsevier Inc</publisher><subject>Animals ; Antibiotics, Antineoplastic - administration & dosage ; Antibiotics, Antineoplastic - pharmacokinetics ; Antibiotics, Antineoplastic - therapeutic use ; Biological and medical sciences ; doxorubicin ; Doxorubicin - administration & dosage ; Doxorubicin - pharmacokinetics ; Doxorubicin - therapeutic use ; drug delivery ; Drug Delivery Systems - instrumentation ; Drug Delivery Systems - methods ; General pharmacology ; Medical sciences ; Micelles ; Neoplasms - drug therapy ; Pharmaceutical technology. Pharmaceutical industry ; pharmacokinetics ; Pharmacology. Drug treatments ; rat tumor model ; Rats ; Ultrasonics ; ultrasound</subject><ispartof>Journal of pharmaceutical sciences, 2010-07, Vol.99 (7), p.3122-3131</ispartof><rights>2010 Wiley-Liss, Inc.</rights><rights>Copyright © 2010 Wiley‐Liss, Inc.</rights><rights>2015 INIST-CNRS</rights><rights>(c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6258-60299304fc4508dca7a4a7b5a4794b212f7ff406e2bc9d9f75f46d015e3a26223</citedby><cites>FETCH-LOGICAL-c6258-60299304fc4508dca7a4a7b5a4794b212f7ff406e2bc9d9f75f46d015e3a26223</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjps.22088$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjps.22088$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22940668$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20166203$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Staples, Bryant J.</creatorcontrib><creatorcontrib>Pitt, William G.</creatorcontrib><creatorcontrib>Roeder, Beverly L.</creatorcontrib><creatorcontrib>Husseini, Ghaleb A.</creatorcontrib><creatorcontrib>Rajeev, Deepthi</creatorcontrib><creatorcontrib>Bruce Schaalje, G.</creatorcontrib><title>Distribution of Doxorubicin in Rats Undergoing Ultrasonic Drug Delivery</title><title>Journal of pharmaceutical sciences</title><addtitle>J. Pharm. Sci</addtitle><description>Ultrasound (US) increases efficacy of drugs delivered from micelles, but the pharmacokinetics have not been studied previously. In this study, US was used to deliver doxorubicin (Dox) sequestered in micelles in an in vivo rat model with bilateral leg tumors. One of two frequencies with identical mechanical index and intensity was delivered for 15min to one tumor immediately after systemic injection of micellar Dox. Pharmacokinetics in myocardium, liver, skeletal muscle, and tumors were measured for 1 week. When applied in combination with micellar Dox, the ultrasoincated tumor had higher Dox concentrations at 30min, compared to bilateral noninsonated controls. Initially, concentrations were highest in heart and liver, but within 24h they decreased significantly. From 24h to 7 days, concentrations remained highest in tumors, regardless of whether they received US or not. Comparison of insonated and noninsonated tumors showed 50% more Dox in the insonated tumor at 30min posttreatment. Four weekly treatment produced additional Dox accumulation in the myocardium but not in liver, skeletal leg muscle, or tumors compared to single treatment. Controls showed that neither US nor the empty carrier impacted tumor growth. This study shows that US causes more release of drug at the targeted tumor. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3122–3131, 2010</description><subject>Animals</subject><subject>Antibiotics, Antineoplastic - administration & dosage</subject><subject>Antibiotics, Antineoplastic - pharmacokinetics</subject><subject>Antibiotics, Antineoplastic - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>doxorubicin</subject><subject>Doxorubicin - administration & dosage</subject><subject>Doxorubicin - pharmacokinetics</subject><subject>Doxorubicin - therapeutic use</subject><subject>drug delivery</subject><subject>Drug Delivery Systems - instrumentation</subject><subject>Drug Delivery Systems - methods</subject><subject>General pharmacology</subject><subject>Medical sciences</subject><subject>Micelles</subject><subject>Neoplasms - drug therapy</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>pharmacokinetics</subject><subject>Pharmacology. Drug treatments</subject><subject>rat tumor model</subject><subject>Rats</subject><subject>Ultrasonics</subject><subject>ultrasound</subject><issn>0022-3549</issn><issn>1520-6017</issn><issn>1520-6017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kV9v0zAUxS0EYmXwwBdAeUGCh2yO_yV-QZoa6KiqgoCKR8tx7OKR2sVOyvrt8ZauDGlIlvxwf_eec88F4GUBzwoI0fnVNp4hBKvqEZgUFMGcwaJ8DCaphnJMCT8Bz2K8ghAySOlTcIJgwRiCeAJmtY19sM3QW-8yb7LaX_swNFZZl6X3RfYxW7lWh7W3bp2tuj7I6J1VWR2GdVbrzu502D8HT4zson5x-E_B6sP7b9PLfPFp9nF6scgVQ7RKxhDnGBKjCIVVq2QpiSwbKknJSYMKZEpjCGQaNYq33JTUENbCgmosEUMIn4J349zt0Gx0q7RLfjqxDXYjw154acW_FWd_iLXfCUIxrhBLA94cBgT_a9CxFxsble466bQfoigw5xySklUJfTuiKvgYgzZHmQKKm-BFCl7cBp_YV_d9Hcm7pBPw-gDIqGRngnTKxr8c4mntW9HzkfttO73_v6KYf_56J52PHemS-vrYIcNPwUpcUvF9ORNLMl3U8-Vc8MTjkdfpTjurg4jKaqd0a4NWvWi9fWDBP_gHuzQ</recordid><startdate>201007</startdate><enddate>201007</enddate><creator>Staples, Bryant J.</creator><creator>Pitt, William G.</creator><creator>Roeder, Beverly L.</creator><creator>Husseini, Ghaleb A.</creator><creator>Rajeev, Deepthi</creator><creator>Bruce Schaalje, G.</creator><general>Elsevier Inc</general><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><general>American Pharmaceutical Association</general><scope>BSCLL</scope><scope>IQODW</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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>201007</creationdate><title>Distribution of Doxorubicin in Rats Undergoing Ultrasonic Drug Delivery</title><author>Staples, Bryant J. ; Pitt, William G. ; Roeder, Beverly L. ; Husseini, Ghaleb A. ; Rajeev, Deepthi ; Bruce Schaalje, G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6258-60299304fc4508dca7a4a7b5a4794b212f7ff406e2bc9d9f75f46d015e3a26223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Antibiotics, Antineoplastic - administration & dosage</topic><topic>Antibiotics, Antineoplastic - pharmacokinetics</topic><topic>Antibiotics, Antineoplastic - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>doxorubicin</topic><topic>Doxorubicin - administration & dosage</topic><topic>Doxorubicin - pharmacokinetics</topic><topic>Doxorubicin - therapeutic use</topic><topic>drug delivery</topic><topic>Drug Delivery Systems - instrumentation</topic><topic>Drug Delivery Systems - methods</topic><topic>General pharmacology</topic><topic>Medical sciences</topic><topic>Micelles</topic><topic>Neoplasms - drug therapy</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>pharmacokinetics</topic><topic>Pharmacology. Drug treatments</topic><topic>rat tumor model</topic><topic>Rats</topic><topic>Ultrasonics</topic><topic>ultrasound</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Staples, Bryant J.</creatorcontrib><creatorcontrib>Pitt, William G.</creatorcontrib><creatorcontrib>Roeder, Beverly L.</creatorcontrib><creatorcontrib>Husseini, Ghaleb A.</creatorcontrib><creatorcontrib>Rajeev, Deepthi</creatorcontrib><creatorcontrib>Bruce Schaalje, G.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of pharmaceutical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Staples, Bryant J.</au><au>Pitt, William G.</au><au>Roeder, Beverly L.</au><au>Husseini, Ghaleb A.</au><au>Rajeev, Deepthi</au><au>Bruce Schaalje, G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Distribution of Doxorubicin in Rats Undergoing Ultrasonic Drug Delivery</atitle><jtitle>Journal of pharmaceutical sciences</jtitle><addtitle>J. Pharm. Sci</addtitle><date>2010-07</date><risdate>2010</risdate><volume>99</volume><issue>7</issue><spage>3122</spage><epage>3131</epage><pages>3122-3131</pages><issn>0022-3549</issn><issn>1520-6017</issn><eissn>1520-6017</eissn><coden>JPMSAE</coden><abstract>Ultrasound (US) increases efficacy of drugs delivered from micelles, but the pharmacokinetics have not been studied previously. In this study, US was used to deliver doxorubicin (Dox) sequestered in micelles in an in vivo rat model with bilateral leg tumors. One of two frequencies with identical mechanical index and intensity was delivered for 15min to one tumor immediately after systemic injection of micellar Dox. Pharmacokinetics in myocardium, liver, skeletal muscle, and tumors were measured for 1 week. When applied in combination with micellar Dox, the ultrasoincated tumor had higher Dox concentrations at 30min, compared to bilateral noninsonated controls. Initially, concentrations were highest in heart and liver, but within 24h they decreased significantly. From 24h to 7 days, concentrations remained highest in tumors, regardless of whether they received US or not. Comparison of insonated and noninsonated tumors showed 50% more Dox in the insonated tumor at 30min posttreatment. Four weekly treatment produced additional Dox accumulation in the myocardium but not in liver, skeletal leg muscle, or tumors compared to single treatment. Controls showed that neither US nor the empty carrier impacted tumor growth. This study shows that US causes more release of drug at the targeted tumor. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3122–3131, 2010</abstract><cop>Hoboken</cop><pub>Elsevier Inc</pub><pmid>20166203</pmid><doi>10.1002/jps.22088</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of pharmaceutical sciences, 2010-07, Vol.99 (7), p.3122-3131 |
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| subjects | Animals Antibiotics, Antineoplastic - administration & dosage Antibiotics, Antineoplastic - pharmacokinetics Antibiotics, Antineoplastic - therapeutic use Biological and medical sciences doxorubicin Doxorubicin - administration & dosage Doxorubicin - pharmacokinetics Doxorubicin - therapeutic use drug delivery Drug Delivery Systems - instrumentation Drug Delivery Systems - methods General pharmacology Medical sciences Micelles Neoplasms - drug therapy Pharmaceutical technology. Pharmaceutical industry pharmacokinetics Pharmacology. Drug treatments rat tumor model Rats Ultrasonics ultrasound |
| title | Distribution of Doxorubicin in Rats Undergoing Ultrasonic Drug Delivery |
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