Self-assembled drug delivery systems. Part 8: In vitro/in vivo studies of the nanoassemblies of cholesteryl-phosphonyl gemcitabine
[Display omitted] A lipid derivative of gemcitabine (Gem), cholesteryl-phosphonyl gemcitabine (CPNG) was synthesized in this study. The amphiphilicity of CPNG was confirmed using a Langmuir monolayer method. Nanoassemblies were formed when the mixture of CPNG and a long-circulating material, CHS-PEG...
Gespeichert in:
| Veröffentlicht in: | International journal of pharmaceutics 2015-01, Vol.478 (1), p.124-130 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 130 |
|---|---|
| container_issue | 1 |
| container_start_page | 124 |
| container_title | International journal of pharmaceutics |
| container_volume | 478 |
| creator | Li, Miao Qi, Shuo Jin, Yiguang Dong, Junxing |
| description | [Display omitted]
A lipid derivative of gemcitabine (Gem), cholesteryl-phosphonyl gemcitabine (CPNG) was synthesized in this study. The amphiphilicity of CPNG was confirmed using a Langmuir monolayer method. Nanoassemblies were formed when the mixture of CPNG and a long-circulating material, CHS-PEG1500 (9:1, mol/mol) were injected into water. The nanoassemblies could be spherical vesicles according to the transmission electron microscopic images. Their mean size was 71.1nm and the zeta potential was −17.6mV. CPNG maintained stable in the weakly acidic and neutral environments although mouse plasma quickly degraded CPNG. The cytotoxicity of the nanoassemblies was 3–6 folds of Gem's cytotoxicity on five human cancer cell lines including 95C, 95D, A549, SW620, PANC-1 probably because of the phosphonyl substitution and amphiphilicity of CPNG. CPNG mainly distributed into the mononuclear macrophage system (including liver and spleen) after bolus intravenous administration of the nanoassemblies into mice though the expected significant long-circulating effect was not shown. The nanoassemblies with the high dose of CPNG showed the statistically higher in vivo anticancer effect than Gem. This study indicates that the N-substituted lipid derivative of Gem and the true long-circulating function are necessary for preparing a successful nanoassembly of Gem. |
| doi_str_mv | 10.1016/j.ijpharm.2014.11.033 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1734281349</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S037851731400845X</els_id><sourcerecordid>1734281349</sourcerecordid><originalsourceid>FETCH-LOGICAL-c365t-325a0aa9a055ef2628439ed5388019d61708c37eeef61a65b649cca8f73af1073</originalsourceid><addsrcrecordid>eNqFkE1v1DAQhi1ERbeFnwDykUtSO7ZjhwtCFf2QKhUJOFtee9L1yokXO1kpV345Xm3gymE0o9E778w8CL2npKaEtjf72u8PO5OGuiGU15TWhLFXaEOVZBXjsn2NNoRJVQkq2SW6ynlPCGkbyt6gy0ZwroTkG_T7O4S-MjnDsA3gsEvzC3YQ_BHSgvOSJxhyjb-ZNGH1CT-O-OinFG_8qThGnKfZecg49njaAR7NGFeztWt3MUBxSUuoDruYS4xLwC8wWD-ZrR_hLbroTcjwbs3X6Ofd1x-3D9XT8_3j7ZenyrJWTBVrhCHGdIYIAX3TNoqzDpxgShHauZZKoiyTANC31LRi2_LOWqN6yUxPiWTX6OPZ95Dir7ncpAefLYRgRohz1oUTbxRlvCtScZbaFHNO0OtD8oNJi6ZEn_DrvV7x6xN-Taku-Mvch3XFvB3A_Zv6y7sIPp8FUB49ekg6Ww-jBecT2Em76P-z4g_vsZsh</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1734281349</pqid></control><display><type>article</type><title>Self-assembled drug delivery systems. Part 8: In vitro/in vivo studies of the nanoassemblies of cholesteryl-phosphonyl gemcitabine</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Li, Miao ; Qi, Shuo ; Jin, Yiguang ; Dong, Junxing</creator><creatorcontrib>Li, Miao ; Qi, Shuo ; Jin, Yiguang ; Dong, Junxing</creatorcontrib><description>[Display omitted]
A lipid derivative of gemcitabine (Gem), cholesteryl-phosphonyl gemcitabine (CPNG) was synthesized in this study. The amphiphilicity of CPNG was confirmed using a Langmuir monolayer method. Nanoassemblies were formed when the mixture of CPNG and a long-circulating material, CHS-PEG1500 (9:1, mol/mol) were injected into water. The nanoassemblies could be spherical vesicles according to the transmission electron microscopic images. Their mean size was 71.1nm and the zeta potential was −17.6mV. CPNG maintained stable in the weakly acidic and neutral environments although mouse plasma quickly degraded CPNG. The cytotoxicity of the nanoassemblies was 3–6 folds of Gem's cytotoxicity on five human cancer cell lines including 95C, 95D, A549, SW620, PANC-1 probably because of the phosphonyl substitution and amphiphilicity of CPNG. CPNG mainly distributed into the mononuclear macrophage system (including liver and spleen) after bolus intravenous administration of the nanoassemblies into mice though the expected significant long-circulating effect was not shown. The nanoassemblies with the high dose of CPNG showed the statistically higher in vivo anticancer effect than Gem. This study indicates that the N-substituted lipid derivative of Gem and the true long-circulating function are necessary for preparing a successful nanoassembly of Gem.</description><identifier>ISSN: 0378-5173</identifier><identifier>EISSN: 1873-3476</identifier><identifier>DOI: 10.1016/j.ijpharm.2014.11.033</identifier><identifier>PMID: 25448574</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject><![CDATA[Animals ; Antimetabolites, Antineoplastic - administration & dosage ; Antimetabolites, Antineoplastic - chemistry ; Antimetabolites, Antineoplastic - pharmacokinetics ; Antimetabolites, Antineoplastic - therapeutic use ; Cell Line, Tumor ; Cell Survival - drug effects ; Cholesterol - administration & dosage ; Cholesterol - analogs & derivatives ; Cholesterol - chemistry ; Cholesterol - pharmacokinetics ; Cholesterol - therapeutic use ; Deoxycytidine - administration & dosage ; Deoxycytidine - analogs & derivatives ; Deoxycytidine - chemistry ; Deoxycytidine - pharmacokinetics ; Deoxycytidine - therapeutic use ; Drug Delivery Systems ; Gemcitabine ; Humans ; Mice ; Molecular self-assembly ; Nanoassemblies ; Nanostructures - administration & dosage ; Nanostructures - chemistry ; Nanostructures - therapeutic use ; Neoplasms - drug therapy ; Neoplasms - pathology ; Phosphonate ; Prodrug ; Tumor Burden - drug effects]]></subject><ispartof>International journal of pharmaceutics, 2015-01, Vol.478 (1), p.124-130</ispartof><rights>2014</rights><rights>Copyright © 2014. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-325a0aa9a055ef2628439ed5388019d61708c37eeef61a65b649cca8f73af1073</citedby><cites>FETCH-LOGICAL-c365t-325a0aa9a055ef2628439ed5388019d61708c37eeef61a65b649cca8f73af1073</cites><orcidid>0000-0002-3528-1397</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ijpharm.2014.11.033$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25448574$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Miao</creatorcontrib><creatorcontrib>Qi, Shuo</creatorcontrib><creatorcontrib>Jin, Yiguang</creatorcontrib><creatorcontrib>Dong, Junxing</creatorcontrib><title>Self-assembled drug delivery systems. Part 8: In vitro/in vivo studies of the nanoassemblies of cholesteryl-phosphonyl gemcitabine</title><title>International journal of pharmaceutics</title><addtitle>Int J Pharm</addtitle><description>[Display omitted]
A lipid derivative of gemcitabine (Gem), cholesteryl-phosphonyl gemcitabine (CPNG) was synthesized in this study. The amphiphilicity of CPNG was confirmed using a Langmuir monolayer method. Nanoassemblies were formed when the mixture of CPNG and a long-circulating material, CHS-PEG1500 (9:1, mol/mol) were injected into water. The nanoassemblies could be spherical vesicles according to the transmission electron microscopic images. Their mean size was 71.1nm and the zeta potential was −17.6mV. CPNG maintained stable in the weakly acidic and neutral environments although mouse plasma quickly degraded CPNG. The cytotoxicity of the nanoassemblies was 3–6 folds of Gem's cytotoxicity on five human cancer cell lines including 95C, 95D, A549, SW620, PANC-1 probably because of the phosphonyl substitution and amphiphilicity of CPNG. CPNG mainly distributed into the mononuclear macrophage system (including liver and spleen) after bolus intravenous administration of the nanoassemblies into mice though the expected significant long-circulating effect was not shown. The nanoassemblies with the high dose of CPNG showed the statistically higher in vivo anticancer effect than Gem. This study indicates that the N-substituted lipid derivative of Gem and the true long-circulating function are necessary for preparing a successful nanoassembly of Gem.</description><subject>Animals</subject><subject>Antimetabolites, Antineoplastic - administration & dosage</subject><subject>Antimetabolites, Antineoplastic - chemistry</subject><subject>Antimetabolites, Antineoplastic - pharmacokinetics</subject><subject>Antimetabolites, Antineoplastic - therapeutic use</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Cholesterol - administration & dosage</subject><subject>Cholesterol - analogs & derivatives</subject><subject>Cholesterol - chemistry</subject><subject>Cholesterol - pharmacokinetics</subject><subject>Cholesterol - therapeutic use</subject><subject>Deoxycytidine - administration & dosage</subject><subject>Deoxycytidine - analogs & derivatives</subject><subject>Deoxycytidine - chemistry</subject><subject>Deoxycytidine - pharmacokinetics</subject><subject>Deoxycytidine - therapeutic use</subject><subject>Drug Delivery Systems</subject><subject>Gemcitabine</subject><subject>Humans</subject><subject>Mice</subject><subject>Molecular self-assembly</subject><subject>Nanoassemblies</subject><subject>Nanostructures - administration & dosage</subject><subject>Nanostructures - chemistry</subject><subject>Nanostructures - therapeutic use</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - pathology</subject><subject>Phosphonate</subject><subject>Prodrug</subject><subject>Tumor Burden - drug effects</subject><issn>0378-5173</issn><issn>1873-3476</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1v1DAQhi1ERbeFnwDykUtSO7ZjhwtCFf2QKhUJOFtee9L1yokXO1kpV345Xm3gymE0o9E778w8CL2npKaEtjf72u8PO5OGuiGU15TWhLFXaEOVZBXjsn2NNoRJVQkq2SW6ynlPCGkbyt6gy0ZwroTkG_T7O4S-MjnDsA3gsEvzC3YQ_BHSgvOSJxhyjb-ZNGH1CT-O-OinFG_8qThGnKfZecg49njaAR7NGFeztWt3MUBxSUuoDruYS4xLwC8wWD-ZrR_hLbroTcjwbs3X6Ofd1x-3D9XT8_3j7ZenyrJWTBVrhCHGdIYIAX3TNoqzDpxgShHauZZKoiyTANC31LRi2_LOWqN6yUxPiWTX6OPZ95Dir7ncpAefLYRgRohz1oUTbxRlvCtScZbaFHNO0OtD8oNJi6ZEn_DrvV7x6xN-Taku-Mvch3XFvB3A_Zv6y7sIPp8FUB49ekg6Ww-jBecT2Em76P-z4g_vsZsh</recordid><startdate>20150115</startdate><enddate>20150115</enddate><creator>Li, Miao</creator><creator>Qi, Shuo</creator><creator>Jin, Yiguang</creator><creator>Dong, Junxing</creator><general>Elsevier 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>7X8</scope><orcidid>https://orcid.org/0000-0002-3528-1397</orcidid></search><sort><creationdate>20150115</creationdate><title>Self-assembled drug delivery systems. Part 8: In vitro/in vivo studies of the nanoassemblies of cholesteryl-phosphonyl gemcitabine</title><author>Li, Miao ; Qi, Shuo ; Jin, Yiguang ; Dong, Junxing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-325a0aa9a055ef2628439ed5388019d61708c37eeef61a65b649cca8f73af1073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Antimetabolites, Antineoplastic - administration & dosage</topic><topic>Antimetabolites, Antineoplastic - chemistry</topic><topic>Antimetabolites, Antineoplastic - pharmacokinetics</topic><topic>Antimetabolites, Antineoplastic - therapeutic use</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Cholesterol - administration & dosage</topic><topic>Cholesterol - analogs & derivatives</topic><topic>Cholesterol - chemistry</topic><topic>Cholesterol - pharmacokinetics</topic><topic>Cholesterol - therapeutic use</topic><topic>Deoxycytidine - administration & dosage</topic><topic>Deoxycytidine - analogs & derivatives</topic><topic>Deoxycytidine - chemistry</topic><topic>Deoxycytidine - pharmacokinetics</topic><topic>Deoxycytidine - therapeutic use</topic><topic>Drug Delivery Systems</topic><topic>Gemcitabine</topic><topic>Humans</topic><topic>Mice</topic><topic>Molecular self-assembly</topic><topic>Nanoassemblies</topic><topic>Nanostructures - administration & dosage</topic><topic>Nanostructures - chemistry</topic><topic>Nanostructures - therapeutic use</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - pathology</topic><topic>Phosphonate</topic><topic>Prodrug</topic><topic>Tumor Burden - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Miao</creatorcontrib><creatorcontrib>Qi, Shuo</creatorcontrib><creatorcontrib>Jin, Yiguang</creatorcontrib><creatorcontrib>Dong, Junxing</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of pharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Miao</au><au>Qi, Shuo</au><au>Jin, Yiguang</au><au>Dong, Junxing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Self-assembled drug delivery systems. Part 8: In vitro/in vivo studies of the nanoassemblies of cholesteryl-phosphonyl gemcitabine</atitle><jtitle>International journal of pharmaceutics</jtitle><addtitle>Int J Pharm</addtitle><date>2015-01-15</date><risdate>2015</risdate><volume>478</volume><issue>1</issue><spage>124</spage><epage>130</epage><pages>124-130</pages><issn>0378-5173</issn><eissn>1873-3476</eissn><abstract>[Display omitted]
A lipid derivative of gemcitabine (Gem), cholesteryl-phosphonyl gemcitabine (CPNG) was synthesized in this study. The amphiphilicity of CPNG was confirmed using a Langmuir monolayer method. Nanoassemblies were formed when the mixture of CPNG and a long-circulating material, CHS-PEG1500 (9:1, mol/mol) were injected into water. The nanoassemblies could be spherical vesicles according to the transmission electron microscopic images. Their mean size was 71.1nm and the zeta potential was −17.6mV. CPNG maintained stable in the weakly acidic and neutral environments although mouse plasma quickly degraded CPNG. The cytotoxicity of the nanoassemblies was 3–6 folds of Gem's cytotoxicity on five human cancer cell lines including 95C, 95D, A549, SW620, PANC-1 probably because of the phosphonyl substitution and amphiphilicity of CPNG. CPNG mainly distributed into the mononuclear macrophage system (including liver and spleen) after bolus intravenous administration of the nanoassemblies into mice though the expected significant long-circulating effect was not shown. The nanoassemblies with the high dose of CPNG showed the statistically higher in vivo anticancer effect than Gem. This study indicates that the N-substituted lipid derivative of Gem and the true long-circulating function are necessary for preparing a successful nanoassembly of Gem.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>25448574</pmid><doi>10.1016/j.ijpharm.2014.11.033</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-3528-1397</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0378-5173 |
| ispartof | International journal of pharmaceutics, 2015-01, Vol.478 (1), p.124-130 |
| issn | 0378-5173 1873-3476 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1734281349 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Antimetabolites, Antineoplastic - administration & dosage Antimetabolites, Antineoplastic - chemistry Antimetabolites, Antineoplastic - pharmacokinetics Antimetabolites, Antineoplastic - therapeutic use Cell Line, Tumor Cell Survival - drug effects Cholesterol - administration & dosage Cholesterol - analogs & derivatives Cholesterol - chemistry Cholesterol - pharmacokinetics Cholesterol - therapeutic use Deoxycytidine - administration & dosage Deoxycytidine - analogs & derivatives Deoxycytidine - chemistry Deoxycytidine - pharmacokinetics Deoxycytidine - therapeutic use Drug Delivery Systems Gemcitabine Humans Mice Molecular self-assembly Nanoassemblies Nanostructures - administration & dosage Nanostructures - chemistry Nanostructures - therapeutic use Neoplasms - drug therapy Neoplasms - pathology Phosphonate Prodrug Tumor Burden - drug effects |
| title | Self-assembled drug delivery systems. Part 8: In vitro/in vivo studies of the nanoassemblies of cholesteryl-phosphonyl gemcitabine |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T08%3A07%3A43IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Self-assembled%20drug%20delivery%20systems.%20Part%208:%20In%20vitro/in%20vivo%20studies%20of%20the%20nanoassemblies%20of%20cholesteryl-phosphonyl%20gemcitabine&rft.jtitle=International%20journal%20of%20pharmaceutics&rft.au=Li,%20Miao&rft.date=2015-01-15&rft.volume=478&rft.issue=1&rft.spage=124&rft.epage=130&rft.pages=124-130&rft.issn=0378-5173&rft.eissn=1873-3476&rft_id=info:doi/10.1016/j.ijpharm.2014.11.033&rft_dat=%3Cproquest_cross%3E1734281349%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1734281349&rft_id=info:pmid/25448574&rft_els_id=S037851731400845X&rfr_iscdi=true |