Citric acid is more effective than sodium thiosulfate in chelating calcium in a dissolution model of calcinosis
Abstract Calcinosis cutis affects 20–40% of patients with systemic sclerosis. This study tests the hypothesis that calcium-chelating polycarboxylic acids can induce calcium dissolution without skin toxicity or irritancy. We compared citric acid (CA) and ethylenediaminetetraacetic acid (EDTA) to sodi...
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Nature Portfolio
2024-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-65761-3 |
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| author | Kyle A. Burgess Richard E. P. Winpenny Alberto Saiani Aline F. Miller Ariane L. Herrick Rachel E. B. Watson |
| author_facet | Kyle A. Burgess Richard E. P. Winpenny Alberto Saiani Aline F. Miller Ariane L. Herrick Rachel E. B. Watson |
| author_sort | Kyle A. Burgess |
| collection | DOAJ |
| description | Abstract Calcinosis cutis affects 20–40% of patients with systemic sclerosis. This study tests the hypothesis that calcium-chelating polycarboxylic acids can induce calcium dissolution without skin toxicity or irritancy. We compared citric acid (CA) and ethylenediaminetetraacetic acid (EDTA) to sodium thiosulfate (STS) for their ability to chelate calcium in vitro using a pharmaceutical dissolution model of calcinosis (hydroxyapatite (HAp) tablet), prior to evaluation of toxicity and irritancy in 2D in vitro skin models. Resultant data was used to predict therapeutic concentrations for application in a validated 3D skin irritation model (SkinEthic™; EpiSkin SA) and to assay maximal percutaneous absorption. Dissolution performance was further assessed via ability to dissolve a calcified matrix laid down in vitro. Pharmacological dissolution studies identified that polycarboxylic acids were superior to STS in dissolving HAp tablets. In vitro, compounds had little effect on cell numbers at concentrations of < 10 mM. When applied topically to 3D models as near-saturated solutions, chelators were not irritant nor did they impact model structure histologically. CA was the most efficient chelator of calcium salts. This study highlights polycarboxylic acids, particularly CA, as potential therapies to target calcinosis cutis: these should now be investigated in human studies. |
| format | Article |
| id | doaj-art-c4f8ceec09ba4d7ca85689d798137dfa |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-c4f8ceec09ba4d7ca85689d798137dfa2024-12-29T12:18:39ZengNature PortfolioScientific Reports2045-23222024-12-0114111010.1038/s41598-024-65761-3Citric acid is more effective than sodium thiosulfate in chelating calcium in a dissolution model of calcinosisKyle A. Burgess0Richard E. P. Winpenny1Alberto Saiani2Aline F. Miller3Ariane L. Herrick4Rachel E. B. Watson5Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester and Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science CentreDepartment of Chemistry, The University of ManchesterDepartment of Materials, The University of ManchesterManchester Institute of Biotechnology, Department of Chemical Engineering, School of Engineering, The University of ManchesterDivision of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester and Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science CentreDivision of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester and Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science CentreAbstract Calcinosis cutis affects 20–40% of patients with systemic sclerosis. This study tests the hypothesis that calcium-chelating polycarboxylic acids can induce calcium dissolution without skin toxicity or irritancy. We compared citric acid (CA) and ethylenediaminetetraacetic acid (EDTA) to sodium thiosulfate (STS) for their ability to chelate calcium in vitro using a pharmaceutical dissolution model of calcinosis (hydroxyapatite (HAp) tablet), prior to evaluation of toxicity and irritancy in 2D in vitro skin models. Resultant data was used to predict therapeutic concentrations for application in a validated 3D skin irritation model (SkinEthic™; EpiSkin SA) and to assay maximal percutaneous absorption. Dissolution performance was further assessed via ability to dissolve a calcified matrix laid down in vitro. Pharmacological dissolution studies identified that polycarboxylic acids were superior to STS in dissolving HAp tablets. In vitro, compounds had little effect on cell numbers at concentrations of < 10 mM. When applied topically to 3D models as near-saturated solutions, chelators were not irritant nor did they impact model structure histologically. CA was the most efficient chelator of calcium salts. This study highlights polycarboxylic acids, particularly CA, as potential therapies to target calcinosis cutis: these should now be investigated in human studies.https://doi.org/10.1038/s41598-024-65761-3 |
| spellingShingle | Kyle A. Burgess Richard E. P. Winpenny Alberto Saiani Aline F. Miller Ariane L. Herrick Rachel E. B. Watson Citric acid is more effective than sodium thiosulfate in chelating calcium in a dissolution model of calcinosis Scientific Reports |
| title | Citric acid is more effective than sodium thiosulfate in chelating calcium in a dissolution model of calcinosis |
| title_full | Citric acid is more effective than sodium thiosulfate in chelating calcium in a dissolution model of calcinosis |
| title_fullStr | Citric acid is more effective than sodium thiosulfate in chelating calcium in a dissolution model of calcinosis |
| title_full_unstemmed | Citric acid is more effective than sodium thiosulfate in chelating calcium in a dissolution model of calcinosis |
| title_short | Citric acid is more effective than sodium thiosulfate in chelating calcium in a dissolution model of calcinosis |
| title_sort | citric acid is more effective than sodium thiosulfate in chelating calcium in a dissolution model of calcinosis |
| url | https://doi.org/10.1038/s41598-024-65761-3 |
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