Controlled destabilization of a liposomal drug delivery system enhances mitoxantrone antitumor activity
Programmable fusogenic vesicles (PFVs) are lipid-based drug-delivery systems that exhibit time-dependent destabilization. The rate at which this destabilization occurs is determined by the exchange rate of a bilayer-stabilizing component, polyethylene glycol-phosphatidylethanolamine (PEG-PE) from th...
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| Veröffentlicht in: | Nature biotechnology 1999-08, Vol.17 (8), p.775-779 |
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| container_title | Nature biotechnology |
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| creator | Adlakha-Hutcheon, Gitanjali Bally, Marcel B. Shew, Clifford R. Madden, Thomas D. |
| description | Programmable fusogenic vesicles (PFVs) are lipid-based drug-delivery systems that exhibit time-dependent destabilization. The rate at which this destabilization occurs is determined by the exchange rate of a bilayer-stabilizing component, polyethylene glycol-phosphatidylethanolamine (PEG-PE) from the vesicle surface. This exchange rate is controlled, in turn, by the acyl chain composition of the PEG-PE. We describe in vitro and in vivo studies using PFVs as delivery vehicles for the anticancer drug mitoxantrone. We demonstrate that the PEG-PE acyl composition determined the rate at which PFVs are eliminated from plasma after intravenous administration, and the rate of mitoxantrone leakage from PFV. The nature of the PEG-PE component also determined the antitumor efficacy of mitoxantrone-loaded PFV in murine and human in murine and human xenograft tumor models. Increased circulation time and improved activity were obtained for PFV containing PEG-PE with an 18-carbon acyl chain length, as a result of slower vesicle destabilization. |
| doi_str_mv | 10.1038/11710 |
| format | Article |
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The rate at which this destabilization occurs is determined by the exchange rate of a bilayer-stabilizing component, polyethylene glycol-phosphatidylethanolamine (PEG-PE) from the vesicle surface. This exchange rate is controlled, in turn, by the acyl chain composition of the PEG-PE. We describe in vitro and in vivo studies using PFVs as delivery vehicles for the anticancer drug mitoxantrone. We demonstrate that the PEG-PE acyl composition determined the rate at which PFVs are eliminated from plasma after intravenous administration, and the rate of mitoxantrone leakage from PFV. The nature of the PEG-PE component also determined the antitumor efficacy of mitoxantrone-loaded PFV in murine and human in murine and human xenograft tumor models. Increased circulation time and improved activity were obtained for PFV containing PEG-PE with an 18-carbon acyl chain length, as a result of slower vesicle destabilization.</description><identifier>ISSN: 1087-0156</identifier><identifier>EISSN: 1546-1696</identifier><identifier>DOI: 10.1038/11710</identifier><identifier>PMID: 10429242</identifier><identifier>CODEN: NABIF9</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Agriculture ; Animals ; Antineoplastic Agents - pharmacokinetics ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Bioinformatics ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedical Engineering/Biotechnology ; Biomedicine ; Biotechnology ; Cell Line ; Drug Carriers ; Female ; Fundamental and applied biological sciences. Psychology ; Health. Pharmaceutical industry ; Humans ; Industrial applications and implications. Economical aspects ; Life Sciences ; Liposomes ; Mice ; Miscellaneous ; Mitoxantrone - pharmacokinetics ; Mitoxantrone - pharmacology ; Mitoxantrone - therapeutic use ; Neoplasms - drug therapy ; Neoplasms - metabolism ; research-article ; Tissue Distribution ; Tumor Cells, Cultured</subject><ispartof>Nature biotechnology, 1999-08, Vol.17 (8), p.775-779</ispartof><rights>Nature America Inc. 1999</rights><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c364t-f64e974d2bec090532a0de083dd530523abae123e0ba68e5a71a6bd9a7f948db3</citedby><cites>FETCH-LOGICAL-c364t-f64e974d2bec090532a0de083dd530523abae123e0ba68e5a71a6bd9a7f948db3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/11710$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/11710$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1943639$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10429242$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Adlakha-Hutcheon, Gitanjali</creatorcontrib><creatorcontrib>Bally, Marcel B.</creatorcontrib><creatorcontrib>Shew, Clifford R.</creatorcontrib><creatorcontrib>Madden, Thomas D.</creatorcontrib><title>Controlled destabilization of a liposomal drug delivery system enhances mitoxantrone antitumor activity</title><title>Nature biotechnology</title><addtitle>Nat Biotechnol</addtitle><addtitle>Nat Biotechnol</addtitle><description>Programmable fusogenic vesicles (PFVs) are lipid-based drug-delivery systems that exhibit time-dependent destabilization. The rate at which this destabilization occurs is determined by the exchange rate of a bilayer-stabilizing component, polyethylene glycol-phosphatidylethanolamine (PEG-PE) from the vesicle surface. This exchange rate is controlled, in turn, by the acyl chain composition of the PEG-PE. We describe in vitro and in vivo studies using PFVs as delivery vehicles for the anticancer drug mitoxantrone. We demonstrate that the PEG-PE acyl composition determined the rate at which PFVs are eliminated from plasma after intravenous administration, and the rate of mitoxantrone leakage from PFV. The nature of the PEG-PE component also determined the antitumor efficacy of mitoxantrone-loaded PFV in murine and human in murine and human xenograft tumor models. Increased circulation time and improved activity were obtained for PFV containing PEG-PE with an 18-carbon acyl chain length, as a result of slower vesicle destabilization.</description><subject>Agriculture</subject><subject>Animals</subject><subject>Antineoplastic Agents - pharmacokinetics</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Bioinformatics</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering/Biotechnology</subject><subject>Biomedicine</subject><subject>Biotechnology</subject><subject>Cell Line</subject><subject>Drug Carriers</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Health. Pharmaceutical industry</subject><subject>Humans</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Life Sciences</subject><subject>Liposomes</subject><subject>Mice</subject><subject>Miscellaneous</subject><subject>Mitoxantrone - pharmacokinetics</subject><subject>Mitoxantrone - pharmacology</subject><subject>Mitoxantrone - therapeutic use</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - metabolism</subject><subject>research-article</subject><subject>Tissue Distribution</subject><subject>Tumor Cells, Cultured</subject><issn>1087-0156</issn><issn>1546-1696</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMFu2zAMhoWhw5pmfYVBh3Y3b5Ily9axCNq1QIBdtrNBW3SmQrZSSQ6aPf3UJUCKXnoiAX74SX6EXHL2jTPRfOe85uwDWfBKqoIrrc5yz5q6YLxS5-QixkfGmJJKfSLnnMlSl7JckM3KTyl459BQgzFBZ539C8n6ifqBAnV266MfwVET5k1mnN1h2NO4jwlHitMfmHqMdLTJP8NL1oQ0V5vm0QcKfbI7m_afyccBXMTLY12S33e3v1b3xfrnj4fVzbrohZKpGJREXUtTdtgzzSpRAjPIGmFMJVhVCugAeSmQdaAarKDmoDqjoR60bEwnluTrIXcb_NOcH2pHG3t0Dib0c2yV1iIH1e-CvBalbiTP4PUB7IOPMeDQboMdIexbztoX9e1_9Zn7cgycuxHNK-rgOgNXRwBiD24IWZyNJ05LoYQ-HRbzZNpgaB_9HKYs7c3Cf8NKmQo</recordid><startdate>19990801</startdate><enddate>19990801</enddate><creator>Adlakha-Hutcheon, Gitanjali</creator><creator>Bally, Marcel B.</creator><creator>Shew, Clifford R.</creator><creator>Madden, Thomas D.</creator><general>Nature Publishing Group US</general><general>Nature</general><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>7X8</scope></search><sort><creationdate>19990801</creationdate><title>Controlled destabilization of a liposomal drug delivery system enhances mitoxantrone antitumor activity</title><author>Adlakha-Hutcheon, Gitanjali ; Bally, Marcel B. ; Shew, Clifford R. ; Madden, Thomas D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c364t-f64e974d2bec090532a0de083dd530523abae123e0ba68e5a71a6bd9a7f948db3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Agriculture</topic><topic>Animals</topic><topic>Antineoplastic Agents - pharmacokinetics</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Bioinformatics</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical Engineering/Biotechnology</topic><topic>Biomedicine</topic><topic>Biotechnology</topic><topic>Cell Line</topic><topic>Drug Carriers</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Health. Pharmaceutical industry</topic><topic>Humans</topic><topic>Industrial applications and implications. Economical aspects</topic><topic>Life Sciences</topic><topic>Liposomes</topic><topic>Mice</topic><topic>Miscellaneous</topic><topic>Mitoxantrone - pharmacokinetics</topic><topic>Mitoxantrone - pharmacology</topic><topic>Mitoxantrone - therapeutic use</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - metabolism</topic><topic>research-article</topic><topic>Tissue Distribution</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Adlakha-Hutcheon, Gitanjali</creatorcontrib><creatorcontrib>Bally, Marcel B.</creatorcontrib><creatorcontrib>Shew, Clifford R.</creatorcontrib><creatorcontrib>Madden, Thomas D.</creatorcontrib><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>MEDLINE - Academic</collection><jtitle>Nature biotechnology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Adlakha-Hutcheon, Gitanjali</au><au>Bally, Marcel B.</au><au>Shew, Clifford R.</au><au>Madden, Thomas D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Controlled destabilization of a liposomal drug delivery system enhances mitoxantrone antitumor activity</atitle><jtitle>Nature biotechnology</jtitle><stitle>Nat Biotechnol</stitle><addtitle>Nat Biotechnol</addtitle><date>1999-08-01</date><risdate>1999</risdate><volume>17</volume><issue>8</issue><spage>775</spage><epage>779</epage><pages>775-779</pages><issn>1087-0156</issn><eissn>1546-1696</eissn><coden>NABIF9</coden><abstract>Programmable fusogenic vesicles (PFVs) are lipid-based drug-delivery systems that exhibit time-dependent destabilization. The rate at which this destabilization occurs is determined by the exchange rate of a bilayer-stabilizing component, polyethylene glycol-phosphatidylethanolamine (PEG-PE) from the vesicle surface. This exchange rate is controlled, in turn, by the acyl chain composition of the PEG-PE. We describe in vitro and in vivo studies using PFVs as delivery vehicles for the anticancer drug mitoxantrone. We demonstrate that the PEG-PE acyl composition determined the rate at which PFVs are eliminated from plasma after intravenous administration, and the rate of mitoxantrone leakage from PFV. The nature of the PEG-PE component also determined the antitumor efficacy of mitoxantrone-loaded PFV in murine and human in murine and human xenograft tumor models. 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| subjects | Agriculture Animals Antineoplastic Agents - pharmacokinetics Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Bioinformatics Biological and medical sciences Biomedical and Life Sciences Biomedical Engineering/Biotechnology Biomedicine Biotechnology Cell Line Drug Carriers Female Fundamental and applied biological sciences. Psychology Health. Pharmaceutical industry Humans Industrial applications and implications. Economical aspects Life Sciences Liposomes Mice Miscellaneous Mitoxantrone - pharmacokinetics Mitoxantrone - pharmacology Mitoxantrone - therapeutic use Neoplasms - drug therapy Neoplasms - metabolism research-article Tissue Distribution Tumor Cells, Cultured |
| title | Controlled destabilization of a liposomal drug delivery system enhances mitoxantrone antitumor activity |
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