Therapeutic Efficacy of 5-Fluorouracil Prodrugs Using Endogenous Serum Proteins as Drug Carriers : A New Strategy in Drug Delivery System
To establish a novel drug delivery system for 5-fluorouracil (5FU), we have developed a system in which the low-molecular-weight prodrugs of 5FU bound to endogenous serum proteins, thus circulating like those proteins. Subsequently, the prodrugs were slowly hydrolyzed to generate active 5FU in the b...
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| Veröffentlicht in: | Biological & pharmaceutical bulletin 1995/01/15, Vol.18(1), pp.181-184 |
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| creator | OKU, Naoto YAMASHITA, Shinji SAKURAGI, Naoko DOI, Kanako OKADA, Shoji SHIMIDZU, Kenji SUMI, Masao NADAI, Tanekazu KUSUMOTO, Shoichi SUDA, Yasuo |
| description | To establish a novel drug delivery system for 5-fluorouracil (5FU), we have developed a system in which the low-molecular-weight prodrugs of 5FU bound to endogenous serum proteins, thus circulating like those proteins. Subsequently, the prodrugs were slowly hydrolyzed to generate active 5FU in the bloodstream. To examine the therapeutic effect of these prodrugs, we injected them into BALB/c mice previously implanted subcutaneously with Meth A sarcoma. Among the prodrugs, 1-(N-4-chlorophenyl-N-methylcarbamoyl)-5-fluorouracil (5FU-1pCPMC) was effective in reducing tumors and prolonging survival time. The non-hydrolyzable compound, 1-(4-chlorobenzyl)-5-fluorouracil, did not show any therapeutic effect, suggesting that the therapeutic efficacy of 5FU-1pCPMC is due to the sustained release of 5FU from the serum protein-prodrug complex. The data shown here may create a new field in drug delivery system technology. |
| doi_str_mv | 10.1248/bpb.18.181 |
| format | Article |
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Subsequently, the prodrugs were slowly hydrolyzed to generate active 5FU in the bloodstream. To examine the therapeutic effect of these prodrugs, we injected them into BALB/c mice previously implanted subcutaneously with Meth A sarcoma. Among the prodrugs, 1-(N-4-chlorophenyl-N-methylcarbamoyl)-5-fluorouracil (5FU-1pCPMC) was effective in reducing tumors and prolonging survival time. The non-hydrolyzable compound, 1-(4-chlorobenzyl)-5-fluorouracil, did not show any therapeutic effect, suggesting that the therapeutic efficacy of 5FU-1pCPMC is due to the sustained release of 5FU from the serum protein-prodrug complex. The data shown here may create a new field in drug delivery system technology.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.18.181</identifier><identifier>PMID: 7735239</identifier><language>eng</language><publisher>Tokyo: The Pharmaceutical Society of Japan</publisher><subject>5-fluorouracil prodrug ; Animals ; Antineoplastic agents ; Biological and medical sciences ; Blood Proteins - metabolism ; Drug Carriers ; drug delivery ; Drug Delivery Systems ; Fluorouracil - administration & dosage ; Fluorouracil - analogs & derivatives ; Fluorouracil - therapeutic use ; General aspects ; long-circulating ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Neoplasm Transplantation ; Pharmacology. Drug treatments ; Prodrugs - administration & dosage ; Prodrugs - therapeutic use ; Sarcoma, Experimental - drug therapy ; Sarcoma, Experimental - pathology</subject><ispartof>Biological and Pharmaceutical Bulletin, 1995/01/15, Vol.18(1), pp.181-184</ispartof><rights>The Pharmaceutical Society of Japan</rights><rights>1995 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c574t-2f201b92b2b8635f275956ed510e2ae483d4abb4ce3051593c3c067c7ffcc6e43</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3499105$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7735239$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>OKU, Naoto</creatorcontrib><creatorcontrib>YAMASHITA, Shinji</creatorcontrib><creatorcontrib>SAKURAGI, Naoko</creatorcontrib><creatorcontrib>DOI, Kanako</creatorcontrib><creatorcontrib>OKADA, Shoji</creatorcontrib><creatorcontrib>SHIMIDZU, Kenji</creatorcontrib><creatorcontrib>SUMI, Masao</creatorcontrib><creatorcontrib>NADAI, Tanekazu</creatorcontrib><creatorcontrib>KUSUMOTO, Shoichi</creatorcontrib><creatorcontrib>SUDA, Yasuo</creatorcontrib><title>Therapeutic Efficacy of 5-Fluorouracil Prodrugs Using Endogenous Serum Proteins as Drug Carriers : A New Strategy in Drug Delivery System</title><title>Biological & pharmaceutical bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>To establish a novel drug delivery system for 5-fluorouracil (5FU), we have developed a system in which the low-molecular-weight prodrugs of 5FU bound to endogenous serum proteins, thus circulating like those proteins. Subsequently, the prodrugs were slowly hydrolyzed to generate active 5FU in the bloodstream. To examine the therapeutic effect of these prodrugs, we injected them into BALB/c mice previously implanted subcutaneously with Meth A sarcoma. Among the prodrugs, 1-(N-4-chlorophenyl-N-methylcarbamoyl)-5-fluorouracil (5FU-1pCPMC) was effective in reducing tumors and prolonging survival time. The non-hydrolyzable compound, 1-(4-chlorobenzyl)-5-fluorouracil, did not show any therapeutic effect, suggesting that the therapeutic efficacy of 5FU-1pCPMC is due to the sustained release of 5FU from the serum protein-prodrug complex. The data shown here may create a new field in drug delivery system technology.</description><subject>5-fluorouracil prodrug</subject><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Blood Proteins - metabolism</subject><subject>Drug Carriers</subject><subject>drug delivery</subject><subject>Drug Delivery Systems</subject><subject>Fluorouracil - administration & dosage</subject><subject>Fluorouracil - analogs & derivatives</subject><subject>Fluorouracil - therapeutic use</subject><subject>General aspects</subject><subject>long-circulating</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Neoplasm Transplantation</subject><subject>Pharmacology. Drug treatments</subject><subject>Prodrugs - administration & dosage</subject><subject>Prodrugs - therapeutic use</subject><subject>Sarcoma, Experimental - drug therapy</subject><subject>Sarcoma, Experimental - pathology</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kU1v1DAQhi0EKkvhwh3JB9QDUoo_4jjmVm23BakCpG3PkeOMU1f5WMYJKD-Bf423u6w0mjk8j2bk14S85-ySi7z8XO_qS16m4i_IistcZ0pw9ZKsmOFlVnBVviZvYnxijGkm5Bk501oqIc2K_L1_BLQ7mKfg6Mb74Kxb6Oipym66ecRxRutCR3_i2ODcRvoQw9DSzdCMLQzjHOkWcO73fIIwRGojvU4iXVvEABjpF3pFv8Mfup3QTtAuNAwH4xq68BtwodslTtC_Ja-87SK8O85z8nCzuV9_ze5-3H5bX91lTul8yoQXjNdG1KIuC6m80MqoAhrFGQgLeSmb3NZ17kAyxZWRTjpWaKe9d66AXJ6Ti8PeHY6_ZohT1YfooOvsAOk9ldZCMVGaJH46iA7HGBF8tcPQW1wqzqp97lXKveJlKp7kD8etc91Dc1KPQSf-8chtdLbzaAcX4kmTuTGcqaStD9pTnGwLJ24x_U8H-4vcGPl89X_jJ-oeLVYwyH8L8aNz</recordid><startdate>19950101</startdate><enddate>19950101</enddate><creator>OKU, Naoto</creator><creator>YAMASHITA, Shinji</creator><creator>SAKURAGI, Naoko</creator><creator>DOI, Kanako</creator><creator>OKADA, Shoji</creator><creator>SHIMIDZU, Kenji</creator><creator>SUMI, Masao</creator><creator>NADAI, Tanekazu</creator><creator>KUSUMOTO, Shoichi</creator><creator>SUDA, Yasuo</creator><general>The Pharmaceutical Society of Japan</general><general>Maruzen</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>7X8</scope></search><sort><creationdate>19950101</creationdate><title>Therapeutic Efficacy of 5-Fluorouracil Prodrugs Using Endogenous Serum Proteins as Drug Carriers : A New Strategy in Drug Delivery System</title><author>OKU, Naoto ; YAMASHITA, Shinji ; SAKURAGI, Naoko ; DOI, Kanako ; OKADA, Shoji ; SHIMIDZU, Kenji ; SUMI, Masao ; NADAI, Tanekazu ; KUSUMOTO, Shoichi ; SUDA, Yasuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c574t-2f201b92b2b8635f275956ed510e2ae483d4abb4ce3051593c3c067c7ffcc6e43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>5-fluorouracil prodrug</topic><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Blood Proteins - metabolism</topic><topic>Drug Carriers</topic><topic>drug delivery</topic><topic>Drug Delivery Systems</topic><topic>Fluorouracil - administration & dosage</topic><topic>Fluorouracil - analogs & derivatives</topic><topic>Fluorouracil - therapeutic use</topic><topic>General aspects</topic><topic>long-circulating</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Neoplasm Transplantation</topic><topic>Pharmacology. Drug treatments</topic><topic>Prodrugs - administration & dosage</topic><topic>Prodrugs - therapeutic use</topic><topic>Sarcoma, Experimental - drug therapy</topic><topic>Sarcoma, Experimental - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>OKU, Naoto</creatorcontrib><creatorcontrib>YAMASHITA, Shinji</creatorcontrib><creatorcontrib>SAKURAGI, Naoko</creatorcontrib><creatorcontrib>DOI, Kanako</creatorcontrib><creatorcontrib>OKADA, Shoji</creatorcontrib><creatorcontrib>SHIMIDZU, Kenji</creatorcontrib><creatorcontrib>SUMI, Masao</creatorcontrib><creatorcontrib>NADAI, Tanekazu</creatorcontrib><creatorcontrib>KUSUMOTO, Shoichi</creatorcontrib><creatorcontrib>SUDA, Yasuo</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>MEDLINE - Academic</collection><jtitle>Biological & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>OKU, Naoto</au><au>YAMASHITA, Shinji</au><au>SAKURAGI, Naoko</au><au>DOI, Kanako</au><au>OKADA, Shoji</au><au>SHIMIDZU, Kenji</au><au>SUMI, Masao</au><au>NADAI, Tanekazu</au><au>KUSUMOTO, Shoichi</au><au>SUDA, Yasuo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Therapeutic Efficacy of 5-Fluorouracil Prodrugs Using Endogenous Serum Proteins as Drug Carriers : A New Strategy in Drug Delivery System</atitle><jtitle>Biological & pharmaceutical bulletin</jtitle><addtitle>Biol Pharm Bull</addtitle><date>1995-01-01</date><risdate>1995</risdate><volume>18</volume><issue>1</issue><spage>181</spage><epage>184</epage><pages>181-184</pages><issn>0918-6158</issn><eissn>1347-5215</eissn><abstract>To establish a novel drug delivery system for 5-fluorouracil (5FU), we have developed a system in which the low-molecular-weight prodrugs of 5FU bound to endogenous serum proteins, thus circulating like those proteins. 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| ispartof | Biological and Pharmaceutical Bulletin, 1995/01/15, Vol.18(1), pp.181-184 |
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| source | J-STAGE Free; MEDLINE; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | 5-fluorouracil prodrug Animals Antineoplastic agents Biological and medical sciences Blood Proteins - metabolism Drug Carriers drug delivery Drug Delivery Systems Fluorouracil - administration & dosage Fluorouracil - analogs & derivatives Fluorouracil - therapeutic use General aspects long-circulating Medical sciences Mice Mice, Inbred BALB C Neoplasm Transplantation Pharmacology. Drug treatments Prodrugs - administration & dosage Prodrugs - therapeutic use Sarcoma, Experimental - drug therapy Sarcoma, Experimental - pathology |
| title | Therapeutic Efficacy of 5-Fluorouracil Prodrugs Using Endogenous Serum Proteins as Drug Carriers : A New Strategy in Drug Delivery System |
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