Development of PLGA Nanoparticles Simultaneously Loaded with Vincristine and Verapamil for Treatment of Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is one of the malignant tumors with poor chemo-sensitivity to vincristine sulfate (VCR) due to multi-drug resistance (MDR). Combinations of encapsulated VCR and verapamil hydrochloride (VRP, a chemo-sensitizer) might be a potential strategy to improve HCC therapeutic e...
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| Veröffentlicht in: | Journal of pharmaceutical sciences 2010-12, Vol.99 (12), p.4874-4879 |
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| creator | Song, Xiang Rong Zheng, Yu He, Gu Yang, Li Luo, You Fu He, Zhi Yao Li, Shuang Zhi Li, Jun Ming Yu, Shui Luo, Xun Hou, Shi Xiang Wei, Yu Quan |
| description | Hepatocellular carcinoma (HCC) is one of the malignant tumors with poor chemo-sensitivity to vincristine sulfate (VCR) due to multi-drug resistance (MDR). Combinations of encapsulated VCR and verapamil hydrochloride (VRP, a chemo-sensitizer) might be a potential strategy to improve HCC therapeutic efficacy of VCR. PLGA nanoparticles (PLGANPs) simultaneously loaded with VCR and VRP (CVn) were prepared. The entrapment efficiencies of VCR and VRP were 70.92±3.78% and 85.78±3.23%, respectively (n=3). The HCC therapeutic activity of CVn was assessed using MTT assay. In BEL7402 and BEL7402/5-FU human hepatocarcinoma cell lines, CVn had the same antitumor effect as one free drug/another agent-loaded PLGANPs (C+Vn or Cn+V) combination and coadministration of two singleagent-loaded PLGANPs (Cn+Vn), which was slightly higher than that of the free VCR/VRP combination (C—V). CVn might cause lower normal tissue drug toxicity by the enhanced permeation and retention effect in vivo. Additionally, CVn might cause fewer drug-drug interaction and be the most potential formulation to simultaneously deliver VCR and VRP to the target cell in vivo than the other three nanoparticle formulations (C+Vn, Cn+V, and Cn+Vn). Therefore, we speculate that CVn might be the most effective preparation in the treatment of drug-resistant human HCC in vivo. |
| doi_str_mv | 10.1002/jps.22200 |
| format | Article |
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Combinations of encapsulated VCR and verapamil hydrochloride (VRP, a chemo-sensitizer) might be a potential strategy to improve HCC therapeutic efficacy of VCR. PLGA nanoparticles (PLGANPs) simultaneously loaded with VCR and VRP (CVn) were prepared. The entrapment efficiencies of VCR and VRP were 70.92±3.78% and 85.78±3.23%, respectively (n=3). The HCC therapeutic activity of CVn was assessed using MTT assay. In BEL7402 and BEL7402/5-FU human hepatocarcinoma cell lines, CVn had the same antitumor effect as one free drug/another agent-loaded PLGANPs (C+Vn or Cn+V) combination and coadministration of two singleagent-loaded PLGANPs (Cn+Vn), which was slightly higher than that of the free VCR/VRP combination (C—V). CVn might cause lower normal tissue drug toxicity by the enhanced permeation and retention effect in vivo. Additionally, CVn might cause fewer drug-drug interaction and be the most potential formulation to simultaneously deliver VCR and VRP to the target cell in vivo than the other three nanoparticle formulations (C+Vn, Cn+V, and Cn+Vn). Therefore, we speculate that CVn might be the most effective preparation in the treatment of drug-resistant human HCC in vivo.</description><identifier>ISSN: 0022-3549</identifier><identifier>EISSN: 1520-6017</identifier><identifier>DOI: 10.1002/jps.22200</identifier><identifier>PMID: 20821385</identifier><identifier>CODEN: JPMSAE</identifier><language>eng</language><publisher>Hoboken: Elsevier Inc</publisher><subject>Antineoplastic Agents - toxicity ; Biological and medical sciences ; Carcinoma, Hepatocellular - drug therapy ; Carcinoma, Hepatocellular - metabolism ; Carcinoma, Hepatocellular - pathology ; Cell Line, Tumor ; Chemistry, Pharmaceutical ; Drug Interactions ; Drug Resistance, Multiple - drug effects ; Drug Therapy, Combination ; Fluorouracil - toxicity ; General pharmacology ; hepatocellular carcinoma ; Humans ; Lactic Acid - administration & dosage ; Liver Neoplasms - drug therapy ; Liver Neoplasms - metabolism ; Liver Neoplasms - pathology ; Medical sciences ; multi-drug resistance ; multidrug resistance ; Nanoparticles ; Pharmaceutical Preparations - administration & dosage ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; PLGA nanoparticles ; Polyglycolic Acid - administration & dosage ; Tetrazolium Salts - metabolism ; Thiazoles - metabolism ; verapamil ; Verapamil - administration & dosage ; Verapamil - pharmacology ; vincristine ; Vincristine - administration & dosage ; Vincristine - pharmacology</subject><ispartof>Journal of pharmaceutical sciences, 2010-12, Vol.99 (12), p.4874-4879</ispartof><rights>2010 Wiley-Liss, Inc.</rights><rights>Copyright © 2010 Wiley‐Liss, Inc.</rights><rights>2015 INIST-CNRS</rights><rights>2010 Wiley-Liss, Inc. and the American Pharmacists Association</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4360-f76d95443611dd4f09e8b55305f9c623e83a828503f2442d93e76cb2fc77b04e3</citedby><cites>FETCH-LOGICAL-c4360-f76d95443611dd4f09e8b55305f9c623e83a828503f2442d93e76cb2fc77b04e3</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.22200$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjps.22200$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27915,27916,45565,45566</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23438353$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20821385$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Song, Xiang Rong</creatorcontrib><creatorcontrib>Zheng, Yu</creatorcontrib><creatorcontrib>He, Gu</creatorcontrib><creatorcontrib>Yang, Li</creatorcontrib><creatorcontrib>Luo, You Fu</creatorcontrib><creatorcontrib>He, Zhi Yao</creatorcontrib><creatorcontrib>Li, Shuang Zhi</creatorcontrib><creatorcontrib>Li, Jun Ming</creatorcontrib><creatorcontrib>Yu, Shui</creatorcontrib><creatorcontrib>Luo, Xun</creatorcontrib><creatorcontrib>Hou, Shi Xiang</creatorcontrib><creatorcontrib>Wei, Yu Quan</creatorcontrib><title>Development of PLGA Nanoparticles Simultaneously Loaded with Vincristine and Verapamil for Treatment of Hepatocellular Carcinoma</title><title>Journal of pharmaceutical sciences</title><addtitle>J. Pharm. Sci</addtitle><description>Hepatocellular carcinoma (HCC) is one of the malignant tumors with poor chemo-sensitivity to vincristine sulfate (VCR) due to multi-drug resistance (MDR). Combinations of encapsulated VCR and verapamil hydrochloride (VRP, a chemo-sensitizer) might be a potential strategy to improve HCC therapeutic efficacy of VCR. PLGA nanoparticles (PLGANPs) simultaneously loaded with VCR and VRP (CVn) were prepared. The entrapment efficiencies of VCR and VRP were 70.92±3.78% and 85.78±3.23%, respectively (n=3). The HCC therapeutic activity of CVn was assessed using MTT assay. In BEL7402 and BEL7402/5-FU human hepatocarcinoma cell lines, CVn had the same antitumor effect as one free drug/another agent-loaded PLGANPs (C+Vn or Cn+V) combination and coadministration of two singleagent-loaded PLGANPs (Cn+Vn), which was slightly higher than that of the free VCR/VRP combination (C—V). CVn might cause lower normal tissue drug toxicity by the enhanced permeation and retention effect in vivo. Additionally, CVn might cause fewer drug-drug interaction and be the most potential formulation to simultaneously deliver VCR and VRP to the target cell in vivo than the other three nanoparticle formulations (C+Vn, Cn+V, and Cn+Vn). Therefore, we speculate that CVn might be the most effective preparation in the treatment of drug-resistant human HCC in vivo.</description><subject>Antineoplastic Agents - toxicity</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Hepatocellular - drug therapy</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Cell Line, Tumor</subject><subject>Chemistry, Pharmaceutical</subject><subject>Drug Interactions</subject><subject>Drug Resistance, Multiple - drug effects</subject><subject>Drug Therapy, Combination</subject><subject>Fluorouracil - toxicity</subject><subject>General pharmacology</subject><subject>hepatocellular carcinoma</subject><subject>Humans</subject><subject>Lactic Acid - administration & dosage</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - pathology</subject><subject>Medical sciences</subject><subject>multi-drug resistance</subject><subject>multidrug resistance</subject><subject>Nanoparticles</subject><subject>Pharmaceutical Preparations - administration & dosage</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>PLGA nanoparticles</subject><subject>Polyglycolic Acid - administration & dosage</subject><subject>Tetrazolium Salts - metabolism</subject><subject>Thiazoles - metabolism</subject><subject>verapamil</subject><subject>Verapamil - administration & dosage</subject><subject>Verapamil - pharmacology</subject><subject>vincristine</subject><subject>Vincristine - administration & dosage</subject><subject>Vincristine - pharmacology</subject><issn>0022-3549</issn><issn>1520-6017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1vEzEQhi0EomnhwB9AvnDgsK3XXu_HsUohAUWhUkPhZk3ssXDxrlf2piW3_nS2bFMucJqR5pl5NQ8hb3J2mjPGz276dMo5Z-wZmeWSs6xkefWczMYZz4QsmiNynNINY6xkUr4kR5zVPBe1nJH7C7xFH_oWu4EGSy9Xi3O6hi70EAenPSZ65dqdH6DDsEt-T1cBDBp654Yf9Np1Oro0uA4pdIZeY4QeWuepDZFuIsJwOLzEHoag0fudh0jnELXrQguvyAsLPuHrx3pCvn78sJkvs9WXxaf5-SrThShZZqvSNLIY-zw3prCswXorpWDSNrrkAmsBNa8lE5YXBTeNwKrUW251VW1ZgeKEvJ_u6hhSimhVH10Lca9yph4sqtGi-mNxZN9ObL_btmieyIO2EXj3CEDS4G2ETrv0lxOFqIUUI3c2cXfO4_7_ierz5dUhOps2Rqv462kD4k9VVqKS6tt6oZrlRmy-r1fqIUFMPI7ubh1GlbTDTqNxEfWgTHD_ePA3kDiq9Q</recordid><startdate>201012</startdate><enddate>201012</enddate><creator>Song, Xiang Rong</creator><creator>Zheng, Yu</creator><creator>He, Gu</creator><creator>Yang, Li</creator><creator>Luo, You Fu</creator><creator>He, Zhi Yao</creator><creator>Li, Shuang Zhi</creator><creator>Li, Jun Ming</creator><creator>Yu, Shui</creator><creator>Luo, Xun</creator><creator>Hou, Shi Xiang</creator><creator>Wei, Yu Quan</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></search><sort><creationdate>201012</creationdate><title>Development of PLGA Nanoparticles Simultaneously Loaded with Vincristine and Verapamil for Treatment of Hepatocellular Carcinoma</title><author>Song, Xiang Rong ; Zheng, Yu ; He, Gu ; Yang, Li ; Luo, You Fu ; He, Zhi Yao ; Li, Shuang Zhi ; Li, Jun Ming ; Yu, Shui ; Luo, Xun ; Hou, Shi Xiang ; Wei, Yu Quan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4360-f76d95443611dd4f09e8b55305f9c623e83a828503f2442d93e76cb2fc77b04e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Antineoplastic Agents - toxicity</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Hepatocellular - drug therapy</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Cell Line, Tumor</topic><topic>Chemistry, Pharmaceutical</topic><topic>Drug Interactions</topic><topic>Drug Resistance, Multiple - drug effects</topic><topic>Drug Therapy, Combination</topic><topic>Fluorouracil - toxicity</topic><topic>General pharmacology</topic><topic>hepatocellular carcinoma</topic><topic>Humans</topic><topic>Lactic Acid - administration & dosage</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - pathology</topic><topic>Medical sciences</topic><topic>multi-drug resistance</topic><topic>multidrug resistance</topic><topic>Nanoparticles</topic><topic>Pharmaceutical Preparations - administration & dosage</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>PLGA nanoparticles</topic><topic>Polyglycolic Acid - administration & dosage</topic><topic>Tetrazolium Salts - metabolism</topic><topic>Thiazoles - metabolism</topic><topic>verapamil</topic><topic>Verapamil - administration & dosage</topic><topic>Verapamil - pharmacology</topic><topic>vincristine</topic><topic>Vincristine - administration & dosage</topic><topic>Vincristine - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Song, Xiang Rong</creatorcontrib><creatorcontrib>Zheng, Yu</creatorcontrib><creatorcontrib>He, Gu</creatorcontrib><creatorcontrib>Yang, Li</creatorcontrib><creatorcontrib>Luo, You Fu</creatorcontrib><creatorcontrib>He, Zhi Yao</creatorcontrib><creatorcontrib>Li, Shuang Zhi</creatorcontrib><creatorcontrib>Li, Jun Ming</creatorcontrib><creatorcontrib>Yu, Shui</creatorcontrib><creatorcontrib>Luo, Xun</creatorcontrib><creatorcontrib>Hou, Shi Xiang</creatorcontrib><creatorcontrib>Wei, Yu Quan</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><jtitle>Journal of pharmaceutical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Song, Xiang Rong</au><au>Zheng, Yu</au><au>He, Gu</au><au>Yang, Li</au><au>Luo, You Fu</au><au>He, Zhi Yao</au><au>Li, Shuang Zhi</au><au>Li, Jun Ming</au><au>Yu, Shui</au><au>Luo, Xun</au><au>Hou, Shi Xiang</au><au>Wei, Yu Quan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development of PLGA Nanoparticles Simultaneously Loaded with Vincristine and Verapamil for Treatment of Hepatocellular Carcinoma</atitle><jtitle>Journal of pharmaceutical sciences</jtitle><addtitle>J. Pharm. Sci</addtitle><date>2010-12</date><risdate>2010</risdate><volume>99</volume><issue>12</issue><spage>4874</spage><epage>4879</epage><pages>4874-4879</pages><issn>0022-3549</issn><eissn>1520-6017</eissn><coden>JPMSAE</coden><abstract>Hepatocellular carcinoma (HCC) is one of the malignant tumors with poor chemo-sensitivity to vincristine sulfate (VCR) due to multi-drug resistance (MDR). Combinations of encapsulated VCR and verapamil hydrochloride (VRP, a chemo-sensitizer) might be a potential strategy to improve HCC therapeutic efficacy of VCR. PLGA nanoparticles (PLGANPs) simultaneously loaded with VCR and VRP (CVn) were prepared. The entrapment efficiencies of VCR and VRP were 70.92±3.78% and 85.78±3.23%, respectively (n=3). The HCC therapeutic activity of CVn was assessed using MTT assay. In BEL7402 and BEL7402/5-FU human hepatocarcinoma cell lines, CVn had the same antitumor effect as one free drug/another agent-loaded PLGANPs (C+Vn or Cn+V) combination and coadministration of two singleagent-loaded PLGANPs (Cn+Vn), which was slightly higher than that of the free VCR/VRP combination (C—V). CVn might cause lower normal tissue drug toxicity by the enhanced permeation and retention effect in vivo. Additionally, CVn might cause fewer drug-drug interaction and be the most potential formulation to simultaneously deliver VCR and VRP to the target cell in vivo than the other three nanoparticle formulations (C+Vn, Cn+V, and Cn+Vn). Therefore, we speculate that CVn might be the most effective preparation in the treatment of drug-resistant human HCC in vivo.</abstract><cop>Hoboken</cop><pub>Elsevier Inc</pub><pmid>20821385</pmid><doi>10.1002/jps.22200</doi><tpages>6</tpages></addata></record> |
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| subjects | Antineoplastic Agents - toxicity Biological and medical sciences Carcinoma, Hepatocellular - drug therapy Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - pathology Cell Line, Tumor Chemistry, Pharmaceutical Drug Interactions Drug Resistance, Multiple - drug effects Drug Therapy, Combination Fluorouracil - toxicity General pharmacology hepatocellular carcinoma Humans Lactic Acid - administration & dosage Liver Neoplasms - drug therapy Liver Neoplasms - metabolism Liver Neoplasms - pathology Medical sciences multi-drug resistance multidrug resistance Nanoparticles Pharmaceutical Preparations - administration & dosage Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments PLGA nanoparticles Polyglycolic Acid - administration & dosage Tetrazolium Salts - metabolism Thiazoles - metabolism verapamil Verapamil - administration & dosage Verapamil - pharmacology vincristine Vincristine - administration & dosage Vincristine - pharmacology |
| title | Development of PLGA Nanoparticles Simultaneously Loaded with Vincristine and Verapamil for Treatment of Hepatocellular Carcinoma |
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