Jagiellonian University Repository

Nonclinical evaluation of novel cationically modified polysaccharide antidotes for unfractionated heparin

Nonclinical evaluation of novel cationically modified ...

Show full item record

dc.contributor.author Kałaska, Bartłomiej pl
dc.contributor.author Kamiński, Kamil [SAP14003414] pl
dc.contributor.author Sokolowska, Emilia pl
dc.contributor.author Czaplicki, Dominik [SAP12019892] pl
dc.contributor.author Kujdowicz, Monika [USOS94712] pl
dc.contributor.author Stalińska, Krystyna [SAP12013193] pl
dc.contributor.author Bereta, Joanna [SAP11012315] pl
dc.contributor.author Szczubiałka, Krzysztof [SAP11014318] pl
dc.contributor.author Pawlak, Dariusz pl
dc.contributor.author Nowakowska, Maria [SAP11005597] pl
dc.contributor.author Mogielnicki, Andrzej pl
dc.date.accessioned 2015-05-25T08:01:31Z
dc.date.available 2015-05-25T08:01:31Z
dc.date.issued 2015 pl
dc.identifier.uri http://ruj.uj.edu.pl/xmlui/handle/item/7884
dc.language eng pl
dc.rights Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa *
dc.rights.uri http://creativecommons.org/licenses/by/4.0/pl/legalcode *
dc.title Nonclinical evaluation of novel cationically modified polysaccharide antidotes for unfractionated heparin pl
dc.type JournalArticle pl
dc.identifier.weblink https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0119486&type=printable pl
dc.abstract.en Protamine, the only registered antidote of unfractionated heparin (UFH), may produce a number of adverse effects, such as anaphylactic shock or serious hypotension. We aimed to develop an alternative UFH antidote as efficient as protamine, but safer and easier to produce. As a starting material, we have chosen generally non-toxic, biocompatible, widely available, inexpensive, and easy to functionalize polysaccharides. Our approach was to synthesize, purify and characterize cationic derivatives of dextran, hydroxypropylcellulose, pullulan and γ-cyclodextrin, then to screen them for potential heparin-reversal activity using an in vitro assay and finally examine efficacy and safety of the most active polymers in Wistar rat and BALB/c mouse models of experimentally induced arterial and venous thrombosis. Efficacy studies included the measurement of thrombus formation, activated partial thromboplastin time, bleeding time, and anti-factor Xa activity; safety studies included the measurement of hemodynamic, hematologic and immunologic parameters. Linear, high molecular weight dextran substituted with glycidyltrimethylammonium chloride groups at a ratio of 0.65 per glucose unit (Dex40-GTMAC3) is the most potent and the safest UFH inhibitor showing activity comparable to that of protamine while possessing lower immunogenicity. Cationic polysaccharides of various structures neutralize UFH. Dex40-GTMAC3 is a promising and potentially better UFH antidote than protamine. pl
dc.description.volume 10 pl
dc.description.number 3 pl
dc.identifier.doi 10.1371/journal.pone.0119486 pl
dc.identifier.eissn 1932-6203 pl
dc.title.journal PLoS ONE pl
dc.language.container eng pl
dc.date.accession 2019-02-18 pl
dc.affiliation Wydział Chemii : Zakład Chemii Fizycznej i Elektrochemii pl
dc.affiliation Wydział Biochemii, Biofizyki i Biotechnologii : Zakład Biochemii Komórki pl
dc.subtype Article pl
dc.identifier.articleid e0119486 pl
dc.rights.original CC-BY; otwarte czasopismo; ostateczna wersja wydawcy; w momencie opublikowania; 0; pl
dc.identifier.project ROD UJ / P pl
dc.pbn.affiliation USOS94712:UJ.WCh; pl
.pointsMNiSW [2015 A]: 40

Files in this item

This item appears in the following Collection(s)

Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa Except where otherwise noted, this item's license is described as Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa