Extended blood circulation and joint accumulation of a p(HPMA-co-AzMA)-based nanoconjugate in a murine model of rheumatoid arthritis

Extended blood circulation and joint accumulation of a p(HPMA-co-AzMA)-based nanoconjugate in a murine model of rheumatoid arthritis

BACKGROUNDWe recently synthesized a hydrophilic polymer, poly(N-(2-hydroxypropyl)methacrylamide-co-N-(3-azidopropyl)methacrylamide), p(HPMA-co-AzMA), by RAFT polymerization using a novel azide-containing methacrylamide monomer that through a post modification strategy using click chemistry enabled f...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Molecular and cellular therapies 2014, Vol.2, p.29-29
Hauptverfasser: Ebbesen, Morten F, Bienk, Konrad, Deleuran, Bent W, Howard, Kenneth A
Format: Report
Sprache:eng
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 29
container_issue
container_start_page 29
container_title Molecular and cellular therapies
container_volume 2
creator Ebbesen, Morten F
Bienk, Konrad
Deleuran, Bent W
Howard, Kenneth A
description BACKGROUNDWe recently synthesized a hydrophilic polymer, poly(N-(2-hydroxypropyl)methacrylamide-co-N-(3-azidopropyl)methacrylamide), p(HPMA-co-AzMA), by RAFT polymerization using a novel azide-containing methacrylamide monomer that through a post modification strategy using click chemistry enabled facile preparation of a panel of versatile and well-defined bioconjugates. In this work we screen a panel of different molecular weight (Mw) fluorescently tagged p(HPMA-co-AzMA) in healthy mice, by live bioimaging, to select an extended circulatory half-life material for investigating joint accumulation in a murine collagen antibody-induced arthritis model.FINDINGSFluorescence image analysis revealed half-lifes of
format Report
fullrecord <record><control><sourceid>proquest</sourceid><recordid>TN_cdi_proquest_miscellaneous_1687361330</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1687361330</sourcerecordid><originalsourceid>FETCH-proquest_miscellaneous_16873613303</originalsourceid><addsrcrecordid>eNqVjE1rAjEURUNpoVL9D2-pi0Bm4oxuB7G4EbroXp7JUzMkeTYfULruD6-FFrrt6l4u5547MWlV18r1su3v__RHMct5VEo1qtOrrpmIz-17oWjJwtEzWzAumeqxOI6A0cLILhZAY2r4nfkECNf57mU_SMNy-NgPC3nEfHNEjGw4jvWMhcDdFBBqcpEgsCX_fU0XqgELOwuYyiW54vJUPJzQZ5r95JOYP29fNzt5TfxWKZdDcNmQ9xiJaz40_Xql-0Zrpf-BfgFb9ldc</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>report</recordtype><pqid>1687361330</pqid></control><display><type>report</type><title>Extended blood circulation and joint accumulation of a p(HPMA-co-AzMA)-based nanoconjugate in a murine model of rheumatoid arthritis</title><source>BioMedCentral</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>PubMed Central Open Access</source><source>Springer Nature OA Free Journals</source><creator>Ebbesen, Morten F ; Bienk, Konrad ; Deleuran, Bent W ; Howard, Kenneth A</creator><creatorcontrib>Ebbesen, Morten F ; Bienk, Konrad ; Deleuran, Bent W ; Howard, Kenneth A</creatorcontrib><description>BACKGROUNDWe recently synthesized a hydrophilic polymer, poly(N-(2-hydroxypropyl)methacrylamide-co-N-(3-azidopropyl)methacrylamide), p(HPMA-co-AzMA), by RAFT polymerization using a novel azide-containing methacrylamide monomer that through a post modification strategy using click chemistry enabled facile preparation of a panel of versatile and well-defined bioconjugates. In this work we screen a panel of different molecular weight (Mw) fluorescently tagged p(HPMA-co-AzMA) in healthy mice, by live bioimaging, to select an extended circulatory half-life material for investigating joint accumulation in a murine collagen antibody-induced arthritis model.FINDINGSFluorescence image analysis revealed half-lifes of &lt;20 min, 2.8 h and 6.4 h for p(HPMA-co-AzMA) of 15, 36 and 54 kDa, respectively, with ~10% polymer retained in the blood after 24 h for the highest Mw. p(HPMA-co-AzMA) of 54 kDa showed enhanced accumulation in the joints of the arthritic mouse model with a bioavailability (AUC = 1783% · h) ~12 times higher (P = 0.01) than healthy control (AUC = 148% · h).CONCLUSIONSp(HPMA-co-AzMA) of 54 kDa exhibited extended circulatory half-life and preferential accumulation in inflamed joints of a murine model of rheumatoid arthritis (RA). This combined with well-defined polymer size and versatility for conjugation of a range of biomolecules promotes p(HPMA-co-AzMA) for potential applications in the delivery of drugs for treatment of RA.</description><identifier>ISSN: 2052-8426</identifier><identifier>EISSN: 2052-8426</identifier><language>eng</language><ispartof>Molecular and cellular therapies, 2014, Vol.2, p.29-29</ispartof><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>776,780,4476</link.rule.ids></links><search><creatorcontrib>Ebbesen, Morten F</creatorcontrib><creatorcontrib>Bienk, Konrad</creatorcontrib><creatorcontrib>Deleuran, Bent W</creatorcontrib><creatorcontrib>Howard, Kenneth A</creatorcontrib><title>Extended blood circulation and joint accumulation of a p(HPMA-co-AzMA)-based nanoconjugate in a murine model of rheumatoid arthritis</title><title>Molecular and cellular therapies</title><description>BACKGROUNDWe recently synthesized a hydrophilic polymer, poly(N-(2-hydroxypropyl)methacrylamide-co-N-(3-azidopropyl)methacrylamide), p(HPMA-co-AzMA), by RAFT polymerization using a novel azide-containing methacrylamide monomer that through a post modification strategy using click chemistry enabled facile preparation of a panel of versatile and well-defined bioconjugates. In this work we screen a panel of different molecular weight (Mw) fluorescently tagged p(HPMA-co-AzMA) in healthy mice, by live bioimaging, to select an extended circulatory half-life material for investigating joint accumulation in a murine collagen antibody-induced arthritis model.FINDINGSFluorescence image analysis revealed half-lifes of &lt;20 min, 2.8 h and 6.4 h for p(HPMA-co-AzMA) of 15, 36 and 54 kDa, respectively, with ~10% polymer retained in the blood after 24 h for the highest Mw. p(HPMA-co-AzMA) of 54 kDa showed enhanced accumulation in the joints of the arthritic mouse model with a bioavailability (AUC = 1783% · h) ~12 times higher (P = 0.01) than healthy control (AUC = 148% · h).CONCLUSIONSp(HPMA-co-AzMA) of 54 kDa exhibited extended circulatory half-life and preferential accumulation in inflamed joints of a murine model of rheumatoid arthritis (RA). This combined with well-defined polymer size and versatility for conjugation of a range of biomolecules promotes p(HPMA-co-AzMA) for potential applications in the delivery of drugs for treatment of RA.</description><issn>2052-8426</issn><issn>2052-8426</issn><fulltext>true</fulltext><rsrctype>report</rsrctype><creationdate>2014</creationdate><recordtype>report</recordtype><recordid>eNqVjE1rAjEURUNpoVL9D2-pi0Bm4oxuB7G4EbroXp7JUzMkeTYfULruD6-FFrrt6l4u5547MWlV18r1su3v__RHMct5VEo1qtOrrpmIz-17oWjJwtEzWzAumeqxOI6A0cLILhZAY2r4nfkECNf57mU_SMNy-NgPC3nEfHNEjGw4jvWMhcDdFBBqcpEgsCX_fU0XqgELOwuYyiW54vJUPJzQZ5r95JOYP29fNzt5TfxWKZdDcNmQ9xiJaz40_Xql-0Zrpf-BfgFb9ldc</recordid><startdate>20140101</startdate><enddate>20140101</enddate><creator>Ebbesen, Morten F</creator><creator>Bienk, Konrad</creator><creator>Deleuran, Bent W</creator><creator>Howard, Kenneth A</creator><scope>7X8</scope></search><sort><creationdate>20140101</creationdate><title>Extended blood circulation and joint accumulation of a p(HPMA-co-AzMA)-based nanoconjugate in a murine model of rheumatoid arthritis</title><author>Ebbesen, Morten F ; Bienk, Konrad ; Deleuran, Bent W ; Howard, Kenneth A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-proquest_miscellaneous_16873613303</frbrgroupid><rsrctype>reports</rsrctype><prefilter>reports</prefilter><language>eng</language><creationdate>2014</creationdate><toplevel>online_resources</toplevel><creatorcontrib>Ebbesen, Morten F</creatorcontrib><creatorcontrib>Bienk, Konrad</creatorcontrib><creatorcontrib>Deleuran, Bent W</creatorcontrib><creatorcontrib>Howard, Kenneth A</creatorcontrib><collection>MEDLINE - Academic</collection></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ebbesen, Morten F</au><au>Bienk, Konrad</au><au>Deleuran, Bent W</au><au>Howard, Kenneth A</au><format>book</format><genre>unknown</genre><ristype>RPRT</ristype><atitle>Extended blood circulation and joint accumulation of a p(HPMA-co-AzMA)-based nanoconjugate in a murine model of rheumatoid arthritis</atitle><jtitle>Molecular and cellular therapies</jtitle><date>2014-01-01</date><risdate>2014</risdate><volume>2</volume><spage>29</spage><epage>29</epage><pages>29-29</pages><issn>2052-8426</issn><eissn>2052-8426</eissn><abstract>BACKGROUNDWe recently synthesized a hydrophilic polymer, poly(N-(2-hydroxypropyl)methacrylamide-co-N-(3-azidopropyl)methacrylamide), p(HPMA-co-AzMA), by RAFT polymerization using a novel azide-containing methacrylamide monomer that through a post modification strategy using click chemistry enabled facile preparation of a panel of versatile and well-defined bioconjugates. In this work we screen a panel of different molecular weight (Mw) fluorescently tagged p(HPMA-co-AzMA) in healthy mice, by live bioimaging, to select an extended circulatory half-life material for investigating joint accumulation in a murine collagen antibody-induced arthritis model.FINDINGSFluorescence image analysis revealed half-lifes of &lt;20 min, 2.8 h and 6.4 h for p(HPMA-co-AzMA) of 15, 36 and 54 kDa, respectively, with ~10% polymer retained in the blood after 24 h for the highest Mw. p(HPMA-co-AzMA) of 54 kDa showed enhanced accumulation in the joints of the arthritic mouse model with a bioavailability (AUC = 1783% · h) ~12 times higher (P = 0.01) than healthy control (AUC = 148% · h).CONCLUSIONSp(HPMA-co-AzMA) of 54 kDa exhibited extended circulatory half-life and preferential accumulation in inflamed joints of a murine model of rheumatoid arthritis (RA). This combined with well-defined polymer size and versatility for conjugation of a range of biomolecules promotes p(HPMA-co-AzMA) for potential applications in the delivery of drugs for treatment of RA.</abstract></addata></record>
fulltext fulltext
identifier ISSN: 2052-8426
ispartof Molecular and cellular therapies, 2014, Vol.2, p.29-29
issn 2052-8426
2052-8426
language eng
recordid cdi_proquest_miscellaneous_1687361330
source BioMedCentral; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access; Springer Nature OA Free Journals
title Extended blood circulation and joint accumulation of a p(HPMA-co-AzMA)-based nanoconjugate in a murine model of rheumatoid arthritis
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T19%3A45%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest&rft_val_fmt=info:ofi/fmt:kev:mtx:book&rft.genre=unknown&rft.atitle=Extended%20blood%20circulation%20and%20joint%20accumulation%20of%20a%20p(HPMA-co-AzMA)-based%20nanoconjugate%20in%20a%20murine%20model%20of%20rheumatoid%20arthritis&rft.jtitle=Molecular%20and%20cellular%20therapies&rft.au=Ebbesen,%20Morten%20F&rft.date=2014-01-01&rft.volume=2&rft.spage=29&rft.epage=29&rft.pages=29-29&rft.issn=2052-8426&rft.eissn=2052-8426&rft_id=info:doi/&rft_dat=%3Cproquest%3E1687361330%3C/proquest%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1687361330&rft_id=info:pmid/&rfr_iscdi=true