Iron-carbohydrate complexes treating iron anaemia: Understanding the nano-structure and interactions with proteins through orthogonal characterisation.
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| Titel: | Iron-carbohydrate complexes treating iron anaemia: Understanding the nano-structure and interactions with proteins through orthogonal characterisation. |
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| Autoren: | Krupnik L; Center for X-ray Analytics, Empa, Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, St. Gallen 9014, Switzerland; Particles-Biology Interactions Laboratory, Empa, Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, 9014 St. Gallen, Switzerland; Department of Chemistry, University of Fribourg, Chemin du Musée 9, 1700 Fribourg, Switzerland., Avaro J; Center for X-ray Analytics, Empa, Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, St. Gallen 9014, Switzerland., Liebi M; Photon Science Division, PSI Paul Scherrer Institute, Villigen CH-5232, Switzerland; Institute of Materials, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland., Anaraki NI; Center for X-ray Analytics, Empa, Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, St. Gallen 9014, Switzerland; Particles-Biology Interactions Laboratory, Empa, Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, 9014 St. Gallen, Switzerland; Department of Chemistry, University of Fribourg, Chemin du Musée 9, 1700 Fribourg, Switzerland., Kohlbrecher J; Laboratory for Neutron Scattering, PSI Paul Scherrer Institute, Villigen CH-5232, Switzerland., Sologubenko A; Scientific Center for Optical and Electron Microscopy, ScopeM, ETH Zürich, 8093 Zürich, Switzerland., Handschin S; Scientific Center for Optical and Electron Microscopy, ScopeM, ETH Zürich, 8093 Zürich, Switzerland., Rzepiela AJ; Scientific Center for Optical and Electron Microscopy, ScopeM, ETH Zürich, 8093 Zürich, Switzerland., Appel C; Photon Science Division, PSI Paul Scherrer Institute, Villigen CH-5232, Switzerland., Totu T; Particles-Biology Interactions Laboratory, Empa, Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, 9014 St. Gallen, Switzerland; ETH Zurich, Department of Health Sciences and Technology (D-HEST), CH-8093 Zurich, Switzerland; SIB, Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland., Blanchet CE; European Molecular Biology Laboratory, Hamburg Outstation, Notkestrasse 85, Hamburg 22603, Germany., Alston AEB; CSL Vifor, Flughofstrasse 61, CH-8152 Glattbrugg, Switzerland., Digigow R; CSL Vifor, Flughofstrasse 61, CH-8152 Glattbrugg, Switzerland., Philipp E; CSL Vifor, Flughofstrasse 61, CH-8152 Glattbrugg, Switzerland., Flühmann B; CSL Vifor, Flughofstrasse 61, CH-8152 Glattbrugg, Switzerland., Silva BFB; Center for X-ray Analytics, Empa, Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, St. Gallen 9014, Switzerland., Neels A; Center for X-ray Analytics, Empa, Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, St. Gallen 9014, Switzerland; Department of Chemistry, University of Fribourg, Chemin du Musée 9, 1700 Fribourg, Switzerland. Electronic address: antonia.neels@empa.ch., Wick P; Particles-Biology Interactions Laboratory, Empa, Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, 9014 St. Gallen, Switzerland. Electronic address: peter.wick@empa.ch. |
| Quelle: | Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2024 Apr; Vol. 368, pp. 566-579. Date of Electronic Publication: 2024 Mar 14. |
| Publikationsart: | Journal Article |
| Sprache: | English |
| Info zur Zeitschrift: | Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 8607908 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4995 (Electronic) Linking ISSN: 01683659 NLM ISO Abbreviation: J Control Release Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Amsterdam : Elsevier Science Publishers, 1984- |
| MeSH-Schlagworte: | Anemia, Iron-Deficiency*/drug therapy , Metal Nanoparticles*/chemistry, Maltose/*analogs & derivatives, Humans ; Iron/chemistry ; Scattering, Small Angle ; Ligands ; X-Ray Diffraction ; Ferric Compounds ; Ferric Oxide, Saccharated/therapeutic use ; Fibrinogen |
| Abstract: | Intravenous (IV) iron-carbohydrate complexes are widely used nanoparticles (NPs) to treat iron deficiency anaemia, often associated with medical conditions such as chronic kidney disease, heart failure and various inflammatory conditions. Even though a plethora of physicochemical characterisation data and clinical studies are available for these products, evidence-based correlation between physicochemical properties of iron-carbohydrate complexes and clinical outcome has not fully been elucidated yet. Studies on other metal oxide NPs suggest that early interactions between NPs and blood upon IV injection are key to understanding how differences in physicochemical characteristics of iron-carbohydrate complexes cause variance in clinical outcomes. We therefore investigated the core-ligand structure of two clinically relevant iron-carbohydrate complexes, iron sucrose (IS) and ferric carboxymaltose (FCM), and their interactions with two structurally different human plasma proteins, human serum albumin (HSA) and fibrinogen, using a combination of cryo-scanning transmission electron microscopy (cryo-STEM), x-ray diffraction (XRD), small-angle x-ray scattering (SAXS) and small-angle neutron scattering (SANS). Using this orthogonal approach, we defined the nano-structure, individual building blocks and surface morphology for IS and FCM. Importantly, we revealed significant differences in the surface morphology of the iron-carbohydrate complexes. FCM shows a localised carbohydrate shell around its core, in contrast to IS, which is characterised by a diffuse and dynamic layer of carbohydrate ligand surrounding its core. We hypothesised that such differences in carbohydrate morphology determine the interaction between iron-carbohydrate complexes and proteins and therefore investigated the NPs in the presence of HSA and fibrinogen. Intriguingly, IS showed significant interaction with HSA and fibrinogen, forming NP-protein clusters, while FCM only showed significant interaction with fibrinogen. We postulate that these differences could influence bio-response of the two formulations and their clinical outcome. In conclusion, our study provides orthogonal characterisation of two clinically relevant iron-carbohydrate complexes and first hints at their interaction behaviour with proteins in the human bloodstream, setting a prerequisite towards complete understanding of the correlation between physicochemical properties and clinical outcome. (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.) |
| Contributed Indexing: | Keywords: Iron deficiency anaemia; Iron-carbohydrate complexes; Nanoparticles (NPs); Non-biological complex drugs (NBCDs); Small-angle neutron scattering (SANS); Small-angle x-ray scattering (SAXS) |
| Substance Nomenclature: | E1UOL152H7 (Iron) 0 (Ligands) 6897GXD6OE (ferric carboxymaltose) 0 (Ferric Compounds) FZ7NYF5N8L (Ferric Oxide, Saccharated) 9001-32-5 (Fibrinogen) 69-79-4 (Maltose) |
| Entry Date(s): | Date Created: 20240304 Date Completed: 20240410 Latest Revision: 20240410 |
| Update Code: | 20250114 |
| DOI: | 10.1016/j.jconrel.2024.02.044 |
| PMID: | 38438093 |
| Datenbank: | MEDLINE |
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Nájsť tento článok vo Web of Science | Abstract: | Intravenous (IV) iron-carbohydrate complexes are widely used nanoparticles (NPs) to treat iron deficiency anaemia, often associated with medical conditions such as chronic kidney disease, heart failure and various inflammatory conditions. Even though a plethora of physicochemical characterisation data and clinical studies are available for these products, evidence-based correlation between physicochemical properties of iron-carbohydrate complexes and clinical outcome has not fully been elucidated yet. Studies on other metal oxide NPs suggest that early interactions between NPs and blood upon IV injection are key to understanding how differences in physicochemical characteristics of iron-carbohydrate complexes cause variance in clinical outcomes. We therefore investigated the core-ligand structure of two clinically relevant iron-carbohydrate complexes, iron sucrose (IS) and ferric carboxymaltose (FCM), and their interactions with two structurally different human plasma proteins, human serum albumin (HSA) and fibrinogen, using a combination of cryo-scanning transmission electron microscopy (cryo-STEM), x-ray diffraction (XRD), small-angle x-ray scattering (SAXS) and small-angle neutron scattering (SANS). Using this orthogonal approach, we defined the nano-structure, individual building blocks and surface morphology for IS and FCM. Importantly, we revealed significant differences in the surface morphology of the iron-carbohydrate complexes. FCM shows a localised carbohydrate shell around its core, in contrast to IS, which is characterised by a diffuse and dynamic layer of carbohydrate ligand surrounding its core. We hypothesised that such differences in carbohydrate morphology determine the interaction between iron-carbohydrate complexes and proteins and therefore investigated the NPs in the presence of HSA and fibrinogen. Intriguingly, IS showed significant interaction with HSA and fibrinogen, forming NP-protein clusters, while FCM only showed significant interaction with fibrinogen. We postulate that these differences could influence bio-response of the two formulations and their clinical outcome. In conclusion, our study provides orthogonal characterisation of two clinically relevant iron-carbohydrate complexes and first hints at their interaction behaviour with proteins in the human bloodstream, setting a prerequisite towards complete understanding of the correlation between physicochemical properties and clinical outcome.<br /> (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.) |
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| ISSN: | 1873-4995 |
| DOI: | 10.1016/j.jconrel.2024.02.044 |