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Development and characterization of an innovtive heparin coating to stabilize and protect liposomes against adverse immune reactions
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
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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
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.

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
URN: urn:nbn:se:uu:diva-279417DOI: 10.1016/j.colsurfb.2016.02.014ISI: 000374197700068PubMedID: 26897551OAI: oai:DiVA.org:uu-279417DiVA: diva2:908041
EU, European Research Council, 324275Swedish Research Council, 2013-65X-05647-34-4EU, European Research Council, 602699Swedish Cancer Society
Available from: 2016-03-01 Created: 2016-03-01 Last updated: 2016-06-21Bibliographically approved

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Fromell, KarinEdwards, KatarinaEkdahl, Kristina NNilsson, Bo
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