{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T15:12:26Z","timestamp":1791990746402,"version":"4.4.0"},"reference-count":41,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guerbet"},{"name":"Franco-Thai program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Gadolinium-based contrast agents (GBCA) are widely used in magnetic resonance imaging (MRI) to enhance image contrast by interacting with water molecules, thus improving diagnostic capabilities. However, understanding the residual accumulation of GBCA in tissues after administration remains an area of active research. This highlights the need for advanced analytical techniques capable of investigating interactions between GBCAs and biopolymers, such as type I collagen, which are abundant in the body. Objective: This study explores the interactions of neutral and charged GBCAs with type I collagen under physiological pH conditions (pH 7.4) using Taylor dispersion analysis (TDA) and frontal analysis continuous capillary electrophoresis (FACCE). Methods: Collagen from bovine achilles tendon was ground using a vibratory ball mill to achieve a more uniform particle size and increased surface area. Laser granulometry was employed to characterize the size distributions of both raw and ground collagen suspensions in water. TDA was used to assess the hydrodynamic radius (Rh) of the soluble collagen fraction present in the supernatant. Results: From the TDA and FACCE results, it was shown that there were no significant interactions between the tested GBCAs and either the ground collagen or its soluble fraction at pH 7.4. Interestingly, we also observed that collagen interacts with filtration membranes, indicating that careful selection of membrane material, or the absence of filtration in the experimental protocol, is essential in interaction studies involving collagen. Conclusion: These findings bring valuable insights into the behavior of GBCAs in biological systems with potential implications for clinical applications.<\/jats:p>","DOI":"10.3390\/ph17121633","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T06:24:44Z","timestamp":1733379884000},"page":"1633","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Study of Interactions Between Gadolinium-Based Contrast Agents and Collagen by Taylor Dispersion Analysis and Frontal Analysis Continuous Capillary Electrophoresis"],"prefix":"10.3390","volume":"17","author":[{"given":"Chutintorn","family":"Somnin","sequence":"first","affiliation":[{"name":"IBMM, University of Montpellier, CNRS, ENSCM, 34095 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4209-1337","authenticated-orcid":false,"given":"Joseph","family":"Chamieh","sequence":"additional","affiliation":[{"name":"IBMM, University of Montpellier, CNRS, ENSCM, 34095 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4058-0268","authenticated-orcid":false,"given":"Laurent","family":"Leclercq","sequence":"additional","affiliation":[{"name":"IBMM, University of Montpellier, CNRS, ENSCM, 34095 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4841-7541","authenticated-orcid":false,"given":"Christelle","family":"Medina","sequence":"additional","affiliation":[{"name":"GUERBET, Research and Innovation, 16 rue Jean Chaptal, 93600 Aulnay Sous Bois, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Rousseaux","sequence":"additional","affiliation":[{"name":"GUERBET, Research and Innovation, 16 rue Jean Chaptal, 93600 Aulnay Sous Bois, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6876-175X","authenticated-orcid":false,"given":"Herv\u00e9","family":"Cottet","sequence":"additional","affiliation":[{"name":"IBMM, University of Montpellier, CNRS, ENSCM, 34095 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1097\/RLI.0b013e3181ee5a9e","article-title":"High relaxivity Magnetic Resonance Imaging Contrast Agents part 1","volume":"45","author":"Dumas","year":"2010","journal-title":"Investig. Radiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/0005-2736(94)90250-X","article-title":"The stretch-activated ion channel blocker gadolinium also blocks L-type calcium channels in isolated ventricular myocytes of the guinea-pig","volume":"1191","author":"Lacampagne","year":"1994","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1021\/cr00081a003","article-title":"Paramagnetic metal complexes as water proton relaxation agents for NMR imaging: Theory and design","volume":"87","author":"Lauffer","year":"1987","journal-title":"Chem. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s10534-008-9135-x","article-title":"Efficiency, thermodynamic and kinetic stability of marketed gadolinium chelates and their possible clinical consequences: A critical review","volume":"21","author":"Port","year":"2008","journal-title":"BioMetals"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1007\/s10534-011-9422-9","article-title":"The role of phosphate on Omniscan\u00ae dechelation: An in vitro relaxivity study at pH 7","volume":"24","author":"Caroline","year":"2011","journal-title":"BioMetals"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1038\/s41467-019-09342-3","article-title":"Ligand design strategies to increase stability of gadolinium-based magnetic resonance imaging contrast agents","volume":"10","author":"Clough","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1097\/RLI.0000000000000563","article-title":"Physicochemical and Pharmacokinetic Profiles of Gadopiclenol: A New Macrocyclic Gadolinium Chelate With High T1 Relaxivity","volume":"54","author":"Robic","year":"2019","journal-title":"Investig. Radiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1097\/00004424-199008000-00010","article-title":"Gd-DOTA: Pharmacokinetics and Tolerability After Intravenous Injection into Healthy Volunteers","volume":"25","author":"Chambon","year":"1990","journal-title":"Investig. Radiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1097\/00004424-199407000-00008","article-title":"Pharmacokinetics, Dose Proportionality, and Tolerability of Gadobutrol after Single Intravenous Injection in Healthy Volunteers","volume":"29","author":"Staks","year":"1994","journal-title":"Investig. Radiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1097\/RLI.0000000000000556","article-title":"Assessment of pharmacokinetic, pharmacodynamic profile, and tolerance of gadopiclenol, a new high relaxivity GBCA, in healthy subjects and patients with brain lesions (Phase I\/IIA study)","volume":"54","author":"Hao","year":"2019","journal-title":"Investig. Radiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.clinimag.2020.07.022","article-title":"MRI demonstration of gadolinium deposition in bone after monthly triple-dose gadopentetate dimeglumine and correlation with frequency of hypophosphatemia","volume":"70","author":"Bageac","year":"2021","journal-title":"Clin. Imaging"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e230984","DOI":"10.1148\/radiol.230984","article-title":"Gadolinium-based contrast agent biodistribution and speciation in rats","volume":"309","author":"Fur","year":"2023","journal-title":"Radiology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1002\/rcm.1571","article-title":"Investigation of non-covalent interactions between paramagnetic complexes and human serum albumin by electrospray mass spectrometry","volume":"18","author":"Henrotte","year":"2004","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1007\/s00775-007-0247-5","article-title":"Comprehensive investigation of the non-covalent binding of MRI contrast agents with human serum albumin","volume":"12","author":"Henrotte","year":"2007","journal-title":"J. Biol. Inorg. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1107\/S0907444902020176","article-title":"A new class of gadolinium complexes employed to obtain high-phasing-power heavy-atom derivatives: Results from SAD experiments with hen egg-white lysozyme and urate oxidase from Aspergillus flavus","volume":"59","author":"Girard","year":"2002","journal-title":"Acta Crystallogr. D"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1107\/S0907444901016444","article-title":"Gd-HPDO3A, a complex to obtain high-phasing-power heavy-atom derivatives for SAD and MAD experiments: Results with tetragonal hen egg-white lysozyme","volume":"58","author":"Girard","year":"2001","journal-title":"Acta Crystallogr. D"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/mrm.22214","article-title":"Evidence for weak protein binding of commercial extracellular gadolinium contrast agents","volume":"63","author":"Wang","year":"2010","journal-title":"Magn. Reson. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"14863","DOI":"10.1039\/D0DT03314F","article-title":"Interaction of macrocyclic gadolinium-based MR contrast agents with Type I collagen. Equilibrium and kinetic studies","volume":"49","author":"Guidolin","year":"2020","journal-title":"Dalton Trans."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e202400344","DOI":"10.1002\/chem.202400344","article-title":"[GD(HB-DO3A)]: Equilibrium, dissociation kinetic and structural differences in a simple homolog of [GD(HP-DO3A)] (Prohance\u00ae)","volume":"30","author":"Versolatto","year":"2024","journal-title":"Chem. Eur. J."},{"key":"ref_20","first-page":"001","article-title":"Revised estimate of total collagen in the human body","volume":"3","author":"Smejkal","year":"2017","journal-title":"J. Biomed. Res. Environ. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1021\/cbmi.3c00023","article-title":"Early Detection and Staging of Lung Fibrosis Enabled by Collagen-Targeted MRI Protein Contrast Agent","volume":"1","author":"Ibhagui","year":"2023","journal-title":"Chem. Biomed. Imaging"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13487","DOI":"10.1021\/acs.analchem.7b03806","article-title":"Limits in Size of Taylor Dispersion Analysis: Representation of the different hydrodynamic regimes and application to the Size-Characterization of Cubosomes","volume":"89","author":"Chamieh","year":"2017","journal-title":"Anal. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1006\/jcis.1997.5131","article-title":"Measurements on the diffusion coefficient of colloidal particles by Taylor\u2013Aris Dispersion","volume":"195","author":"Belongia","year":"1997","journal-title":"J. Colloid Interface Sci."},{"key":"ref_24","first-page":"186","article-title":"Dispersion of soluble matter in solvent flowing slowly through a tube","volume":"219","author":"Taylor","year":"1953","journal-title":"Proc. R. Soc. Lond."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ejps.2016.07.015","article-title":"Taylor Dispersion Analysis as a promising tool for assessment of peptide-peptide interactions","volume":"93","author":"Schwach","year":"2016","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6508","DOI":"10.1021\/acs.analchem.1c00420","article-title":"Antigen-Adjuvant Interactions in Vaccines by Taylor Dispersion Analysis: Size characterization and binding parameters","volume":"93","author":"Malburet","year":"2021","journal-title":"Anal. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7216","DOI":"10.1021\/acs.macromol.5b01824","article-title":"Fast characterization of polyplexes by Taylor Dispersion Analysis","volume":"48","author":"Leclercq","year":"2015","journal-title":"Macromolecules"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4070","DOI":"10.1021\/ja100484d","article-title":"Flow induced dispersion analysis quantifies noncovalent interactions in nanoliter samples","volume":"132","author":"Jensen","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Lounis, F.M., Chamieh, J., Leclercq, L., Gonzalez, P., Rossi, J.-C., and Cottet, H. (2018). Effect of Dendrigraft Generation on the Interaction between Anionic Polyelectrolytes and Dendrigraft Poly(l-Lysine). Polymers, 10.","DOI":"10.3390\/polym10010045"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"9728","DOI":"10.1039\/C6SM01811D","article-title":"Modelling and predicting the interactions between oppositely and variously charged polyelectrolytes by frontal analysis continuous capillary electrophoresis","volume":"12","author":"Lounis","year":"2016","journal-title":"J. Soft Matter"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3364","DOI":"10.1021\/acs.biomac.0c00782","article-title":"Study of Interactions between Antigens and Polymeric Adjuvants in Vaccines by Frontal Analysis Continuous Capillary Electrophoresis","volume":"21","author":"Malburet","year":"2020","journal-title":"Biomacromolecules"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6761","DOI":"10.1021\/acs.analchem.5b00934","article-title":"Taking Advantage of Electric Field Induced Bacterial Aggregation for the Study of Interactions between Bacteria and Macromolecules by Capillary Electrophoresis","volume":"87","author":"Sisavath","year":"2015","journal-title":"Anal. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4450","DOI":"10.1021\/la5002144","article-title":"Effect of Dendrimer Generation on the Interactions between Human Serum Albumin and Dendrigraft Polylysines","volume":"30","author":"Sisavath","year":"2014","journal-title":"Langmuir"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9066","DOI":"10.1021\/ac071018w","article-title":"Taylor Dispersion Analysis of mixtures","volume":"79","author":"Cottet","year":"2007","journal-title":"Anal. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Pachence, J.M., Bohrer, M.P., and Kohn, J. (2007). Biodegradable polymers. Principles of Tissue Engineering, Elsevier. [3rd ed.].","DOI":"10.1016\/B978-012370615-7\/50027-5"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1063\/1.438613","article-title":"Translational friction coefficients of rigid, symmetric top macromolecules. Application to circular cylinders","volume":"71","author":"Tirado","year":"1979","journal-title":"J. Chem. Phys."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2679","DOI":"10.1021\/ma802109f","article-title":"Size-Based Characterization of an ionic polydiacetylene by Taylor Dispersion Analysis and Capillary Electrophoresis","volume":"42","author":"Deschamps","year":"2009","journal-title":"Macromolecules"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6591","DOI":"10.1039\/b817343e","article-title":"Pyridine-based lanthanide complexes: Towards bimodal agents operating as near infrared luminescent and MRI reporters","volume":"48","author":"Pellegatti","year":"2008","journal-title":"Chem. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3195","DOI":"10.1039\/b920448b","article-title":"A europium complex with enhanced long-wavelength sensitized luminescent properties","volume":"12","author":"Xue","year":"2010","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"106831","DOI":"10.1016\/j.ejps.2024.106831","article-title":"Taylor dispersion analysis for measurement of diffusivity and size of gadolinium-based contrast agents","volume":"200","author":"Somnin","year":"2024","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Lounis, F., Chamieh, J., Leclercq, L., Gonzalez, P., and Cottet, H. (2017). The Effect of Molar Mass and Charge Density on the Formation of Complexes between Oppositely Charged Polyelectrolytes. Polymers, 9.","DOI":"10.3390\/polym9020050"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/12\/1633\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:47:29Z","timestamp":1760114849000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/12\/1633"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,5]]},"references-count":41,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["ph17121633"],"URL":"https:\/\/doi.org\/10.3390\/ph17121633","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,5]]}}}