Citric acid is more effective than sodium thiosulfate in chelating calcium in a dissolution model of calcinosis

被引：0

作者：

Burgess, Kyle A. ^{[1
,2
]}

Winpenny, Richard E. P. ^{[3
]}

Saiani, Alberto ^{[4
]}

Miller, Aline F. ^{[5
]}

Herrick, Ariane L. ^{[1
,2
,6
]}

Watson, Rachel E. B. ^{[1
,2
,6
,7
]}

机构：

[1] Univ Manchester, Fac Biol Med & Hlth, Sch Biol Sci, Div Musculoskeletal & Dermatol Sci, Manchester M13 9PT, England

[2] Northern Care Alliance NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester M13 9PT, England

[3] Univ Manchester, Dept Chem, Manchester, England

[4] Univ Manchester, Dept Mat, Manchester, England

[5] Univ Manchester, Manchester Inst Biotechnol, Sch Chem, Manchester, Lancs, England

[6] Manchester Univ NHS Fdn Trust, NIHR Manchester Biomed Res Ctr, Manchester Acad Hlth Sci Ctr, Manchester, England

[7] ASTAR, A STAR Skin Res Labs A SRL, Singapore, Singapore

来源：

SCIENTIFIC REPORTS | 2024年 / 14卷 / 01期

关键词：

SKIN; ULCERS;

D O I：

10.1038/s41598-024-65761-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 (TM); 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.

引用

页数：10