Is an Alternative Drug Delivery System Needed for Docetaxel? The Role of Controlling Epimerization in Formulations and Beyond
ABSTRACT Purpose The presence of 7-epidocetaxel in docetaxel injection and in vivo epimerisation has been reported to be the cause for development of tumor resistance to chemotherapy including docetaxel by inducing tumor cell protein cytochrome P450 1B1. The objective of this study was to determine...
Gespeichert in:
| Veröffentlicht in: | Pharmaceutical research 2013-10, Vol.30 (10), p.2675-2693 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2693 |
|---|---|
| container_issue | 10 |
| container_start_page | 2675 |
| container_title | Pharmaceutical research |
| container_volume | 30 |
| creator | Manjappa, Arehalli S. Goel, Peeyush N. Vekataraju, Makam P. Rajesh, Kesarla S. Makwana, Kinjal Ukawala, Mukesh Nikam, Yuvraj Gude, Rajiv P. Murthy, Rayasa S. Ramachandra |
| description | ABSTRACT
Purpose
The presence of 7-epidocetaxel in docetaxel injection and
in vivo
epimerisation has been reported to be the cause for development of tumor resistance to chemotherapy including docetaxel by inducing tumor cell protein cytochrome P450 1B1. The objective of this study was to determine systemic toxicity of Taxotere® containing 10% 7-epidocetaxel and to develop PEGylated liposomal injection that could resist epimerization
in vivo
. Another need for PEGylated liposomal delivery of docetaxel is to avoid reported hypersensitivity reactions of marketed products like Taxotere® and Duopafei® containing high concentration of tween-80.
Methods
The PEGylated liposomes loaded with docetaxel were prepared using thin film hydration method. The
in vivo
toxicity of Taxotere® containing 10% 7-epimer was studied in B16F10 experimental metastasis model.
Results
B16F10 experimental metastasis model using C57BL/6 mice injected with Taxotere® containing 10% 7-epimer showed higher weight loss as compared to Taxotere® containing no epimer at single dose of 40 mg/kg indicating higher systemic toxicity. Incubation of PEGylated liposomes with phosphate buffer saline (pH 7.4) containing 0.1% w/v Tween-80 for 48 h showed better resistance to docetaxel degradation when compared with Taxotere® injection indicating better
in vivo
stability of liposomal docetaxel. In addition, PEGylated liposomes showed enhanced
in vitro
cytotoxicity, against A549 and B16F10 cells, than Taxotere®.
Conclusion
We can therefore expect less
in vivo
conversion of liposomal loaded docetaxel into 7-epimer, more passive targeting to tumor tissues, decreased 7-epimer induced systemic toxicity and tumor resistance to chemotherapy compared to Taxotere®. Further
in vivo
studies are needed to ascertain these facts. |
| doi_str_mv | 10.1007/s11095-013-1093-5 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_1434120111</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3077272251</sourcerecordid><originalsourceid>FETCH-LOGICAL-c402t-56b8cc0518efe4ee1ee8787ac6019bca37099235424a1ff9fbf6e647dc8b29903</originalsourceid><addsrcrecordid>eNp1kU9v1DAQxS1ERZfCB-CCLCGOoZ7EieMTKrstVKpAgiJxsxxnvKRy7K2dVF0kvjve7vLnwslj-Tfved4Q8gLYG2BMnCYAJuuCQVXkoirqR2QBtagKyfi3x2TBRMmLVnA4Jk9TumGMtSD5E3JcVqJuRC0X5OdlotrTMzdh9Hoa7pCu4rymK3S5jlv6ZZsmHOlHxB57akOkq2Bw0vfo3tLr70g_B4c0WLoMforBucGv6flmGDEOP7Jg8HTw9CLEcXYP151fT9_hNvj-GTmy2iV8fjhPyNeL8-vlh-Lq0_vL5dlVYTgrp6JuutYYVkOLFjkiILaiFdo0DGRndCWYlGVV85JrsFbazjbYcNGbtiulZNUJebXX3cRwO2Oa1E2Y87wuKeAVh5IBQKZgT5kYUopo1SYOo45bBUztAlf7wFUOXO0CV3XueXlQnrsR-z8dvxPOwOsDoJPRzkbtzZD-ckLkhT2Yl3su5Se_xvjPF__r_gvsDpjk</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1434120111</pqid></control><display><type>article</type><title>Is an Alternative Drug Delivery System Needed for Docetaxel? The Role of Controlling Epimerization in Formulations and Beyond</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Manjappa, Arehalli S. ; Goel, Peeyush N. ; Vekataraju, Makam P. ; Rajesh, Kesarla S. ; Makwana, Kinjal ; Ukawala, Mukesh ; Nikam, Yuvraj ; Gude, Rajiv P. ; Murthy, Rayasa S. Ramachandra</creator><creatorcontrib>Manjappa, Arehalli S. ; Goel, Peeyush N. ; Vekataraju, Makam P. ; Rajesh, Kesarla S. ; Makwana, Kinjal ; Ukawala, Mukesh ; Nikam, Yuvraj ; Gude, Rajiv P. ; Murthy, Rayasa S. Ramachandra</creatorcontrib><description>ABSTRACT
Purpose
The presence of 7-epidocetaxel in docetaxel injection and
in vivo
epimerisation has been reported to be the cause for development of tumor resistance to chemotherapy including docetaxel by inducing tumor cell protein cytochrome P450 1B1. The objective of this study was to determine systemic toxicity of Taxotere® containing 10% 7-epidocetaxel and to develop PEGylated liposomal injection that could resist epimerization
in vivo
. Another need for PEGylated liposomal delivery of docetaxel is to avoid reported hypersensitivity reactions of marketed products like Taxotere® and Duopafei® containing high concentration of tween-80.
Methods
The PEGylated liposomes loaded with docetaxel were prepared using thin film hydration method. The
in vivo
toxicity of Taxotere® containing 10% 7-epimer was studied in B16F10 experimental metastasis model.
Results
B16F10 experimental metastasis model using C57BL/6 mice injected with Taxotere® containing 10% 7-epimer showed higher weight loss as compared to Taxotere® containing no epimer at single dose of 40 mg/kg indicating higher systemic toxicity. Incubation of PEGylated liposomes with phosphate buffer saline (pH 7.4) containing 0.1% w/v Tween-80 for 48 h showed better resistance to docetaxel degradation when compared with Taxotere® injection indicating better
in vivo
stability of liposomal docetaxel. In addition, PEGylated liposomes showed enhanced
in vitro
cytotoxicity, against A549 and B16F10 cells, than Taxotere®.
Conclusion
We can therefore expect less
in vivo
conversion of liposomal loaded docetaxel into 7-epimer, more passive targeting to tumor tissues, decreased 7-epimer induced systemic toxicity and tumor resistance to chemotherapy compared to Taxotere®. Further
in vivo
studies are needed to ascertain these facts.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1007/s11095-013-1093-5</identifier><identifier>PMID: 23756759</identifier><identifier>CODEN: PHREEB</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Animals ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - adverse effects ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - therapeutic use ; Biochemistry ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedical Engineering and Bioengineering ; Biomedicine ; Cell Line, Tumor ; Cell Survival - drug effects ; Chemistry, Pharmaceutical ; Chemotherapy ; Dermatology ; Drug Carriers - chemistry ; Drug delivery systems ; Drug resistance ; Female ; Humans ; Lipids ; Liposomes ; Medical Law ; Medical sciences ; Melanoma, Experimental - drug therapy ; Melanoma, Experimental - pathology ; Mice ; Mice, Inbred C57BL ; Molecular Structure ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Pharmacology. Drug treatments ; Pharmacology/Toxicology ; Pharmacy ; Polyethylene Glycols - chemistry ; Research Paper ; Solubility ; Stereoisomerism ; Surface Properties ; Taxoids - administration & dosage ; Taxoids - adverse effects ; Taxoids - chemistry ; Taxoids - therapeutic use ; Tumors ; Tumors of the skin and soft tissue. Premalignant lesions</subject><ispartof>Pharmaceutical research, 2013-10, Vol.30 (10), p.2675-2693</ispartof><rights>Springer Science+Business Media New York 2013</rights><rights>2014 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c402t-56b8cc0518efe4ee1ee8787ac6019bca37099235424a1ff9fbf6e647dc8b29903</citedby><cites>FETCH-LOGICAL-c402t-56b8cc0518efe4ee1ee8787ac6019bca37099235424a1ff9fbf6e647dc8b29903</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/s11095-013-1093-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11095-013-1093-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27757311$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23756759$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Manjappa, Arehalli S.</creatorcontrib><creatorcontrib>Goel, Peeyush N.</creatorcontrib><creatorcontrib>Vekataraju, Makam P.</creatorcontrib><creatorcontrib>Rajesh, Kesarla S.</creatorcontrib><creatorcontrib>Makwana, Kinjal</creatorcontrib><creatorcontrib>Ukawala, Mukesh</creatorcontrib><creatorcontrib>Nikam, Yuvraj</creatorcontrib><creatorcontrib>Gude, Rajiv P.</creatorcontrib><creatorcontrib>Murthy, Rayasa S. Ramachandra</creatorcontrib><title>Is an Alternative Drug Delivery System Needed for Docetaxel? The Role of Controlling Epimerization in Formulations and Beyond</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><addtitle>Pharm Res</addtitle><description>ABSTRACT
Purpose
The presence of 7-epidocetaxel in docetaxel injection and
in vivo
epimerisation has been reported to be the cause for development of tumor resistance to chemotherapy including docetaxel by inducing tumor cell protein cytochrome P450 1B1. The objective of this study was to determine systemic toxicity of Taxotere® containing 10% 7-epidocetaxel and to develop PEGylated liposomal injection that could resist epimerization
in vivo
. Another need for PEGylated liposomal delivery of docetaxel is to avoid reported hypersensitivity reactions of marketed products like Taxotere® and Duopafei® containing high concentration of tween-80.
Methods
The PEGylated liposomes loaded with docetaxel were prepared using thin film hydration method. The
in vivo
toxicity of Taxotere® containing 10% 7-epimer was studied in B16F10 experimental metastasis model.
Results
B16F10 experimental metastasis model using C57BL/6 mice injected with Taxotere® containing 10% 7-epimer showed higher weight loss as compared to Taxotere® containing no epimer at single dose of 40 mg/kg indicating higher systemic toxicity. Incubation of PEGylated liposomes with phosphate buffer saline (pH 7.4) containing 0.1% w/v Tween-80 for 48 h showed better resistance to docetaxel degradation when compared with Taxotere® injection indicating better
in vivo
stability of liposomal docetaxel. In addition, PEGylated liposomes showed enhanced
in vitro
cytotoxicity, against A549 and B16F10 cells, than Taxotere®.
Conclusion
We can therefore expect less
in vivo
conversion of liposomal loaded docetaxel into 7-epimer, more passive targeting to tumor tissues, decreased 7-epimer induced systemic toxicity and tumor resistance to chemotherapy compared to Taxotere®. Further
in vivo
studies are needed to ascertain these facts.</description><subject>Animals</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Biochemistry</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering and Bioengineering</subject><subject>Biomedicine</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Chemistry, Pharmaceutical</subject><subject>Chemotherapy</subject><subject>Dermatology</subject><subject>Drug Carriers - chemistry</subject><subject>Drug delivery systems</subject><subject>Drug resistance</subject><subject>Female</subject><subject>Humans</subject><subject>Lipids</subject><subject>Liposomes</subject><subject>Medical Law</subject><subject>Medical sciences</subject><subject>Melanoma, Experimental - drug therapy</subject><subject>Melanoma, Experimental - pathology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Molecular Structure</subject><subject>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</subject><subject>Pharmacology. Drug treatments</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacy</subject><subject>Polyethylene Glycols - chemistry</subject><subject>Research Paper</subject><subject>Solubility</subject><subject>Stereoisomerism</subject><subject>Surface Properties</subject><subject>Taxoids - administration & dosage</subject><subject>Taxoids - adverse effects</subject><subject>Taxoids - chemistry</subject><subject>Taxoids - therapeutic use</subject><subject>Tumors</subject><subject>Tumors of the skin and soft tissue. Premalignant lesions</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kU9v1DAQxS1ERZfCB-CCLCGOoZ7EieMTKrstVKpAgiJxsxxnvKRy7K2dVF0kvjve7vLnwslj-Tfved4Q8gLYG2BMnCYAJuuCQVXkoirqR2QBtagKyfi3x2TBRMmLVnA4Jk9TumGMtSD5E3JcVqJuRC0X5OdlotrTMzdh9Hoa7pCu4rymK3S5jlv6ZZsmHOlHxB57akOkq2Bw0vfo3tLr70g_B4c0WLoMforBucGv6flmGDEOP7Jg8HTw9CLEcXYP151fT9_hNvj-GTmy2iV8fjhPyNeL8-vlh-Lq0_vL5dlVYTgrp6JuutYYVkOLFjkiILaiFdo0DGRndCWYlGVV85JrsFbazjbYcNGbtiulZNUJebXX3cRwO2Oa1E2Y87wuKeAVh5IBQKZgT5kYUopo1SYOo45bBUztAlf7wFUOXO0CV3XueXlQnrsR-z8dvxPOwOsDoJPRzkbtzZD-ckLkhT2Yl3su5Se_xvjPF__r_gvsDpjk</recordid><startdate>20131001</startdate><enddate>20131001</enddate><creator>Manjappa, Arehalli S.</creator><creator>Goel, Peeyush N.</creator><creator>Vekataraju, Makam P.</creator><creator>Rajesh, Kesarla S.</creator><creator>Makwana, Kinjal</creator><creator>Ukawala, Mukesh</creator><creator>Nikam, Yuvraj</creator><creator>Gude, Rajiv P.</creator><creator>Murthy, Rayasa S. Ramachandra</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</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>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></search><sort><creationdate>20131001</creationdate><title>Is an Alternative Drug Delivery System Needed for Docetaxel? The Role of Controlling Epimerization in Formulations and Beyond</title><author>Manjappa, Arehalli S. ; Goel, Peeyush N. ; Vekataraju, Makam P. ; Rajesh, Kesarla S. ; Makwana, Kinjal ; Ukawala, Mukesh ; Nikam, Yuvraj ; Gude, Rajiv P. ; Murthy, Rayasa S. Ramachandra</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c402t-56b8cc0518efe4ee1ee8787ac6019bca37099235424a1ff9fbf6e647dc8b29903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - adverse effects</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Biochemistry</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical Engineering and Bioengineering</topic><topic>Biomedicine</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Chemistry, Pharmaceutical</topic><topic>Chemotherapy</topic><topic>Dermatology</topic><topic>Drug Carriers - chemistry</topic><topic>Drug delivery systems</topic><topic>Drug resistance</topic><topic>Female</topic><topic>Humans</topic><topic>Lipids</topic><topic>Liposomes</topic><topic>Medical Law</topic><topic>Medical sciences</topic><topic>Melanoma, Experimental - drug therapy</topic><topic>Melanoma, Experimental - pathology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Molecular Structure</topic><topic>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</topic><topic>Pharmacology. Drug treatments</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacy</topic><topic>Polyethylene Glycols - chemistry</topic><topic>Research Paper</topic><topic>Solubility</topic><topic>Stereoisomerism</topic><topic>Surface Properties</topic><topic>Taxoids - administration & dosage</topic><topic>Taxoids - adverse effects</topic><topic>Taxoids - chemistry</topic><topic>Taxoids - therapeutic use</topic><topic>Tumors</topic><topic>Tumors of the skin and soft tissue. Premalignant lesions</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Manjappa, Arehalli S.</creatorcontrib><creatorcontrib>Goel, Peeyush N.</creatorcontrib><creatorcontrib>Vekataraju, Makam P.</creatorcontrib><creatorcontrib>Rajesh, Kesarla S.</creatorcontrib><creatorcontrib>Makwana, Kinjal</creatorcontrib><creatorcontrib>Ukawala, Mukesh</creatorcontrib><creatorcontrib>Nikam, Yuvraj</creatorcontrib><creatorcontrib>Gude, Rajiv P.</creatorcontrib><creatorcontrib>Murthy, Rayasa S. Ramachandra</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>ProQuest Central (Corporate)</collection><collection>Proquest Nursing & Allied Health Source</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><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Manjappa, Arehalli S.</au><au>Goel, Peeyush N.</au><au>Vekataraju, Makam P.</au><au>Rajesh, Kesarla S.</au><au>Makwana, Kinjal</au><au>Ukawala, Mukesh</au><au>Nikam, Yuvraj</au><au>Gude, Rajiv P.</au><au>Murthy, Rayasa S. Ramachandra</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Is an Alternative Drug Delivery System Needed for Docetaxel? The Role of Controlling Epimerization in Formulations and Beyond</atitle><jtitle>Pharmaceutical research</jtitle><stitle>Pharm Res</stitle><addtitle>Pharm Res</addtitle><date>2013-10-01</date><risdate>2013</risdate><volume>30</volume><issue>10</issue><spage>2675</spage><epage>2693</epage><pages>2675-2693</pages><issn>0724-8741</issn><eissn>1573-904X</eissn><coden>PHREEB</coden><abstract>ABSTRACT
Purpose
The presence of 7-epidocetaxel in docetaxel injection and
in vivo
epimerisation has been reported to be the cause for development of tumor resistance to chemotherapy including docetaxel by inducing tumor cell protein cytochrome P450 1B1. The objective of this study was to determine systemic toxicity of Taxotere® containing 10% 7-epidocetaxel and to develop PEGylated liposomal injection that could resist epimerization
in vivo
. Another need for PEGylated liposomal delivery of docetaxel is to avoid reported hypersensitivity reactions of marketed products like Taxotere® and Duopafei® containing high concentration of tween-80.
Methods
The PEGylated liposomes loaded with docetaxel were prepared using thin film hydration method. The
in vivo
toxicity of Taxotere® containing 10% 7-epimer was studied in B16F10 experimental metastasis model.
Results
B16F10 experimental metastasis model using C57BL/6 mice injected with Taxotere® containing 10% 7-epimer showed higher weight loss as compared to Taxotere® containing no epimer at single dose of 40 mg/kg indicating higher systemic toxicity. Incubation of PEGylated liposomes with phosphate buffer saline (pH 7.4) containing 0.1% w/v Tween-80 for 48 h showed better resistance to docetaxel degradation when compared with Taxotere® injection indicating better
in vivo
stability of liposomal docetaxel. In addition, PEGylated liposomes showed enhanced
in vitro
cytotoxicity, against A549 and B16F10 cells, than Taxotere®.
Conclusion
We can therefore expect less
in vivo
conversion of liposomal loaded docetaxel into 7-epimer, more passive targeting to tumor tissues, decreased 7-epimer induced systemic toxicity and tumor resistance to chemotherapy compared to Taxotere®. Further
in vivo
studies are needed to ascertain these facts.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>23756759</pmid><doi>10.1007/s11095-013-1093-5</doi><tpages>19</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0724-8741 |
| ispartof | Pharmaceutical research, 2013-10, Vol.30 (10), p.2675-2693 |
| issn | 0724-8741 1573-904X |
| language | eng |
| recordid | cdi_proquest_journals_1434120111 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Animals Antineoplastic Agents - administration & dosage Antineoplastic Agents - adverse effects Antineoplastic Agents - chemistry Antineoplastic Agents - therapeutic use Biochemistry Biological and medical sciences Biomedical and Life Sciences Biomedical Engineering and Bioengineering Biomedicine Cell Line, Tumor Cell Survival - drug effects Chemistry, Pharmaceutical Chemotherapy Dermatology Drug Carriers - chemistry Drug delivery systems Drug resistance Female Humans Lipids Liposomes Medical Law Medical sciences Melanoma, Experimental - drug therapy Melanoma, Experimental - pathology Mice Mice, Inbred C57BL Molecular Structure Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Pharmacology. Drug treatments Pharmacology/Toxicology Pharmacy Polyethylene Glycols - chemistry Research Paper Solubility Stereoisomerism Surface Properties Taxoids - administration & dosage Taxoids - adverse effects Taxoids - chemistry Taxoids - therapeutic use Tumors Tumors of the skin and soft tissue. Premalignant lesions |
| title | Is an Alternative Drug Delivery System Needed for Docetaxel? The Role of Controlling Epimerization in Formulations and Beyond |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-27T15%3A07%3A36IST&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=Is%20an%20Alternative%20Drug%20Delivery%20System%20Needed%20for%20Docetaxel?%20The%20Role%20of%20Controlling%20Epimerization%20in%20Formulations%20and%20Beyond&rft.jtitle=Pharmaceutical%20research&rft.au=Manjappa,%20Arehalli%20S.&rft.date=2013-10-01&rft.volume=30&rft.issue=10&rft.spage=2675&rft.epage=2693&rft.pages=2675-2693&rft.issn=0724-8741&rft.eissn=1573-904X&rft.coden=PHREEB&rft_id=info:doi/10.1007/s11095-013-1093-5&rft_dat=%3Cproquest_cross%3E3077272251%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=1434120111&rft_id=info:pmid/23756759&rfr_iscdi=true |