Galactosylated Micelles for a Ribavirin Prodrug Targeting to Hepatocytes
Polymeric micelles potentially able to carry to hepatocytes a ribavirin (RBV) prodrug, exploiting the presence of carbohydrate receptors, that is, ASGPR, were prepared starting from a galactosylated polylactide-polyaminoacid conjugate. This latter was obtained by chemical reaction of α,β-poly(N-2-hy...
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| Veröffentlicht in: | Biomacromolecules 2013-06, Vol.14 (6), p.1838-1849 |
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| container_title | Biomacromolecules |
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| creator | Craparo, Emanuela F Triolo, Daniela Pitarresi, Giovanna Giammona, Gaetano Cavallaro, Gennara |
| description | Polymeric micelles potentially able to carry to hepatocytes a ribavirin (RBV) prodrug, exploiting the presence of carbohydrate receptors, that is, ASGPR, were prepared starting from a galactosylated polylactide-polyaminoacid conjugate. This latter was obtained by chemical reaction of α,β-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-dl-aspartamide (PHEA-EDA) with polylactic acid (PLA), and subsequent reaction with lactose, obtaining PHEA-EDA-PLA-GAL copolymer. To enhance the entrapment into obtained nanostructures, a hydrophobic RBV prodrug, that is, RBV tripalmitate, was synthesized and its capability to release RBV in the presence of an adequate enzymatic activity was demonstrated. Liver-targeted RBV tripalmitate-loaded micelles were obtained in aqueous media at low PHEA-EDA-PLA-GAL copolymer concentration value with nanometric size. By in vitro experiments, the specificity of RBV tripalmitate-loaded PHEA-EDA-PLA-GAL micelles toward HepG2 was demonstrated by using a competitive inhibition assay in the presence of free GAL. This finding raises hope in terms of future micelles-based liver-targeted drug delivery strategy for the hepatitis C treatment. |
| doi_str_mv | 10.1021/bm4002409 |
| format | Article |
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This latter was obtained by chemical reaction of α,β-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-dl-aspartamide (PHEA-EDA) with polylactic acid (PLA), and subsequent reaction with lactose, obtaining PHEA-EDA-PLA-GAL copolymer. To enhance the entrapment into obtained nanostructures, a hydrophobic RBV prodrug, that is, RBV tripalmitate, was synthesized and its capability to release RBV in the presence of an adequate enzymatic activity was demonstrated. Liver-targeted RBV tripalmitate-loaded micelles were obtained in aqueous media at low PHEA-EDA-PLA-GAL copolymer concentration value with nanometric size. By in vitro experiments, the specificity of RBV tripalmitate-loaded PHEA-EDA-PLA-GAL micelles toward HepG2 was demonstrated by using a competitive inhibition assay in the presence of free GAL. This finding raises hope in terms of future micelles-based liver-targeted drug delivery strategy for the hepatitis C treatment.</description><identifier>ISSN: 1525-7797</identifier><identifier>EISSN: 1526-4602</identifier><identifier>DOI: 10.1021/bm4002409</identifier><identifier>PMID: 23621358</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Aminoacid polymers ; Antiviral Agents - administration & dosage ; Antiviral Agents - chemistry ; Antiviral Agents - pharmacology ; Applied sciences ; Biological and medical sciences ; Exact sciences and technology ; Galactose - chemistry ; General pharmacology ; Hep G2 Cells ; Hepatitis C virus ; Humans ; Liver - drug effects ; Magnetic Resonance Spectroscopy ; Medical sciences ; Micelles ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Physicochemistry of polymers ; Prodrugs ; Ribavirin - administration & dosage ; Ribavirin - chemistry ; Ribavirin - pharmacology ; Spectroscopy, Fourier Transform Infrared ; Synthetic biopolymers</subject><ispartof>Biomacromolecules, 2013-06, Vol.14 (6), p.1838-1849</ispartof><rights>Copyright © 2013 American Chemical Society</rights><rights>2014 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a378t-cfe47d32f2af5cde9133eb46ee384a4ede1f29944cd0e7fc22ce23cb73e5a0fe3</citedby><cites>FETCH-LOGICAL-a378t-cfe47d32f2af5cde9133eb46ee384a4ede1f29944cd0e7fc22ce23cb73e5a0fe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/bm4002409$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/bm4002409$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27461236$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23621358$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Craparo, Emanuela F</creatorcontrib><creatorcontrib>Triolo, Daniela</creatorcontrib><creatorcontrib>Pitarresi, Giovanna</creatorcontrib><creatorcontrib>Giammona, Gaetano</creatorcontrib><creatorcontrib>Cavallaro, Gennara</creatorcontrib><title>Galactosylated Micelles for a Ribavirin Prodrug Targeting to Hepatocytes</title><title>Biomacromolecules</title><addtitle>Biomacromolecules</addtitle><description>Polymeric micelles potentially able to carry to hepatocytes a ribavirin (RBV) prodrug, exploiting the presence of carbohydrate receptors, that is, ASGPR, were prepared starting from a galactosylated polylactide-polyaminoacid conjugate. This latter was obtained by chemical reaction of α,β-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-dl-aspartamide (PHEA-EDA) with polylactic acid (PLA), and subsequent reaction with lactose, obtaining PHEA-EDA-PLA-GAL copolymer. To enhance the entrapment into obtained nanostructures, a hydrophobic RBV prodrug, that is, RBV tripalmitate, was synthesized and its capability to release RBV in the presence of an adequate enzymatic activity was demonstrated. Liver-targeted RBV tripalmitate-loaded micelles were obtained in aqueous media at low PHEA-EDA-PLA-GAL copolymer concentration value with nanometric size. By in vitro experiments, the specificity of RBV tripalmitate-loaded PHEA-EDA-PLA-GAL micelles toward HepG2 was demonstrated by using a competitive inhibition assay in the presence of free GAL. This finding raises hope in terms of future micelles-based liver-targeted drug delivery strategy for the hepatitis C treatment.</description><subject>Aminoacid polymers</subject><subject>Antiviral Agents - administration & dosage</subject><subject>Antiviral Agents - chemistry</subject><subject>Antiviral Agents - pharmacology</subject><subject>Applied sciences</subject><subject>Biological and medical sciences</subject><subject>Exact sciences and technology</subject><subject>Galactose - chemistry</subject><subject>General pharmacology</subject><subject>Hep G2 Cells</subject><subject>Hepatitis C virus</subject><subject>Humans</subject><subject>Liver - drug effects</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Medical sciences</subject><subject>Micelles</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Physicochemistry of polymers</subject><subject>Prodrugs</subject><subject>Ribavirin - administration & dosage</subject><subject>Ribavirin - chemistry</subject><subject>Ribavirin - pharmacology</subject><subject>Spectroscopy, Fourier Transform Infrared</subject><subject>Synthetic biopolymers</subject><issn>1525-7797</issn><issn>1526-4602</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0E1Lw0AQBuBFFFurB_-A7EXQQ3S_kjRHKdoKFUXqOUw2syUlydbdjdB_b2qrvXiaOTzMx0vIJWd3nAl-XzSKMaFYdkSGPBZJpBImjn_6OErTLB2QM-9XjLFMqviUDIRMBJfxeEhmU6hBB-s3NQQs6Uulsa7RU2MdBfpeFfBVuaqlb86WrlvSBbglhqpd0mDpDNcQrN4E9OfkxEDt8WJfR-Tj6XExmUXz1-nz5GEegUzHIdIGVVpKYQSYWJeYcSmxUAmiHCtQWCI3IsuU0iXD1GghNAqpi1RiDMygHJGb3dy1s58d-pA3ld_eDC3azuf9z0oJroTs6e2Oame9d2jytasacJucs3wbXP4XXG-v9mO7osHyT_4m1YPrPQCvoTYOWl35g0tVwnt8cKB9vrKda_s0_ln4DaVpgXc</recordid><startdate>20130610</startdate><enddate>20130610</enddate><creator>Craparo, Emanuela F</creator><creator>Triolo, Daniela</creator><creator>Pitarresi, Giovanna</creator><creator>Giammona, Gaetano</creator><creator>Cavallaro, Gennara</creator><general>American Chemical Society</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></search><sort><creationdate>20130610</creationdate><title>Galactosylated Micelles for a Ribavirin Prodrug Targeting to Hepatocytes</title><author>Craparo, Emanuela F ; Triolo, Daniela ; Pitarresi, Giovanna ; Giammona, Gaetano ; Cavallaro, Gennara</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a378t-cfe47d32f2af5cde9133eb46ee384a4ede1f29944cd0e7fc22ce23cb73e5a0fe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Aminoacid polymers</topic><topic>Antiviral Agents - administration & dosage</topic><topic>Antiviral Agents - chemistry</topic><topic>Antiviral Agents - pharmacology</topic><topic>Applied sciences</topic><topic>Biological and medical sciences</topic><topic>Exact sciences and technology</topic><topic>Galactose - chemistry</topic><topic>General pharmacology</topic><topic>Hep G2 Cells</topic><topic>Hepatitis C virus</topic><topic>Humans</topic><topic>Liver - drug effects</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Medical sciences</topic><topic>Micelles</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Physicochemistry of polymers</topic><topic>Prodrugs</topic><topic>Ribavirin - administration & dosage</topic><topic>Ribavirin - chemistry</topic><topic>Ribavirin - pharmacology</topic><topic>Spectroscopy, Fourier Transform Infrared</topic><topic>Synthetic biopolymers</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Craparo, Emanuela F</creatorcontrib><creatorcontrib>Triolo, Daniela</creatorcontrib><creatorcontrib>Pitarresi, Giovanna</creatorcontrib><creatorcontrib>Giammona, Gaetano</creatorcontrib><creatorcontrib>Cavallaro, Gennara</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><jtitle>Biomacromolecules</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Craparo, Emanuela F</au><au>Triolo, Daniela</au><au>Pitarresi, Giovanna</au><au>Giammona, Gaetano</au><au>Cavallaro, Gennara</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Galactosylated Micelles for a Ribavirin Prodrug Targeting to Hepatocytes</atitle><jtitle>Biomacromolecules</jtitle><addtitle>Biomacromolecules</addtitle><date>2013-06-10</date><risdate>2013</risdate><volume>14</volume><issue>6</issue><spage>1838</spage><epage>1849</epage><pages>1838-1849</pages><issn>1525-7797</issn><eissn>1526-4602</eissn><abstract>Polymeric micelles potentially able to carry to hepatocytes a ribavirin (RBV) prodrug, exploiting the presence of carbohydrate receptors, that is, ASGPR, were prepared starting from a galactosylated polylactide-polyaminoacid conjugate. This latter was obtained by chemical reaction of α,β-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-dl-aspartamide (PHEA-EDA) with polylactic acid (PLA), and subsequent reaction with lactose, obtaining PHEA-EDA-PLA-GAL copolymer. To enhance the entrapment into obtained nanostructures, a hydrophobic RBV prodrug, that is, RBV tripalmitate, was synthesized and its capability to release RBV in the presence of an adequate enzymatic activity was demonstrated. Liver-targeted RBV tripalmitate-loaded micelles were obtained in aqueous media at low PHEA-EDA-PLA-GAL copolymer concentration value with nanometric size. By in vitro experiments, the specificity of RBV tripalmitate-loaded PHEA-EDA-PLA-GAL micelles toward HepG2 was demonstrated by using a competitive inhibition assay in the presence of free GAL. This finding raises hope in terms of future micelles-based liver-targeted drug delivery strategy for the hepatitis C treatment.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>23621358</pmid><doi>10.1021/bm4002409</doi><tpages>12</tpages></addata></record> |
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| subjects | Aminoacid polymers Antiviral Agents - administration & dosage Antiviral Agents - chemistry Antiviral Agents - pharmacology Applied sciences Biological and medical sciences Exact sciences and technology Galactose - chemistry General pharmacology Hep G2 Cells Hepatitis C virus Humans Liver - drug effects Magnetic Resonance Spectroscopy Medical sciences Micelles Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Physicochemistry of polymers Prodrugs Ribavirin - administration & dosage Ribavirin - chemistry Ribavirin - pharmacology Spectroscopy, Fourier Transform Infrared Synthetic biopolymers |
| title | Galactosylated Micelles for a Ribavirin Prodrug Targeting to Hepatocytes |
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