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Development and characterization of an innovative heparin coating to stabilize and protect liposomes against adverse immune reactions
Uppsala University.
ABNOBA GmbH, Germany ; Association for the Promotion of Cancer Therapy, Germany.
ABNOBA GmbH, Germany ; Association for the Promotion of Cancer Therapy, Germany.
Uppsala University.
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2016 (English)In: Colloids and Surfaces B: Biointerfaces, ISSN 0927-7765, E-ISSN 1873-4367, Vol. 141, 576-583 p.Article in journal (Refereed) Published
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Text
Abstract [en]

Liposomes have been recognized as excellent drug delivery systems, but when they come in direct contact with different blood components they may trigger an immediate activation of the innate immune system. The aim of the present study was to produce long-circulating, blood-compatible liposomes by developing a construct of liposomes covered by a novel unique heparin complex (CHC; 70 heparin molecules per complex) to avoid recognition by the innate immune system. Unilamellar, cationic liposomes were produced by hand extrusion through a 100-nm polycarbonate membrane. Coating of liposomes with the macromolecular CHC was accomplished by electrostatic interactions. Dynamic light scattering as well as QCM-D measurements were used to verify the electrostatic deposition of the negatively charged CHC to cationic liposomes. The CHC-coated liposomes did not aggregate when in contact with lepirudin anti coagulated plasma. Unlike previous attempts to coat liposomes with heparin, this technique produced freely moveable heparin strands sticking out from the liposome surface, which exposed AT binding sites reflecting the anticoagulant potentials of the liposomes. In experiments using lepirudin-anticoagulated plasma, CHC-coated liposomes, in contrast to non-coated control liposomes, did not activate the complement system, as evidenced by low C3a and sC5b-9 generation and reduced leakage from the liposomes. In conclusion, we show that liposomes can be successfully coated with the biopolymer CHC, resulting in biocompatible and stable liposomes that have significant application potential. (C) 2016 Elsevier B.V. All rights reserved.

Place, publisher, year, edition, pages
2016. Vol. 141, 576-583 p.
Keyword [en]
Drug delivery system, Cationic liposomes, Surface coating, Novel heparin complex, Complement system
National Category
Biomaterials Science
Research subject
Natural Science, Biomedical Sciences
Identifiers
URN: urn:nbn:se:lnu:diva-53258DOI: 10.1016/j.colsurfb.2016.02.014ISI: 000374197700068PubMedID: 26897551Scopus ID: 2-s2.0-84958291889OAI: oai:DiVA.org:lnu-53258DiVA: diva2:935119
Available from: 2016-06-10 Created: 2016-06-10 Last updated: 2017-02-16Bibliographically approved

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Edwards, KatarinaNilsson Ekdahl, KristinaNilsson, Bo
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CiteExportLink to record
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Citation style
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