title: Cationic derivatives of dextran and hydroxypropylcellulose as novel potential heparin antagonists.
abstract: Cationic derivatives of dextran (Dex) and hydroxypropylcellulose (HPC) were studied as potential alternatives of protamine sulfate (PS) used in the reversal of anticoagulant activity of heparin. The modification was performed by the attachment of cationic groups to the Dex main chain or by grafting short side chains of a polycation onto HPC. The cationic derivatives of these polysaccharides were found to bind heparin with the efficiency increasing with growing degree of cationic modification. The degree of cationic modification and consequently the ζ potential of the polymers do not have to be high to achieve effective heparin binding. The size of the complexes of cationic Dex with unfractionated heparin (UFH) is a few micrometers. For complexes of cationic HPC and UFH the size is much below 1 μm, both below and above the lower critical solution temperature of HPC. None of the cationic polysaccharides studied caused hemolysis. The concentrations of the polymers inducing the aggregation of human erythrocytes in vitro were determined.
authors.affiliation: Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Kraków, Poland.
authors.forename: Kamil
authors.initials: K
authors.lastname: Kamiński
authors.forename: Monika
authors.initials: M
authors.lastname: Płonka
authors.forename: Justyna
authors.initials: J
authors.lastname: Ciejka
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Szczubiałka
authors.forename: Maria
authors.initials: M
authors.lastname: Nowakowska
authors.forename: Barbara
authors.initials: B
authors.lastname: Lorkowska
authors.forename: Ryszard
authors.initials: R
authors.lastname: Korbut
authors.forename: Radosław
authors.initials: R
authors.lastname: Lach
mesh_terms: D002412:Cations; D002482:Cellulose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003911:Dextrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004903:Erythrocyte Aggregation / Q000187:drug effects; D006461:Hemolysis; D006493:Heparin / Q000737:chemistry; D006494:Heparin Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008027:Light; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012542:Scattering, Radiation; D013329:Structure-Activity Relationship
chemical_list: D002412:Cations; D003911:Dextrans; D006494:Heparin Antagonists; D000644:Quaternary Ammonium Compounds; D002482:Cellulose; D006493:Heparin; C008079:hydroxypropylcellulose