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配位化合物作为骨质疏松症的多输送系统。

Coordination Compounds As Multi-Delivery Systems for Osteoporosis.

机构信息

CICECO-Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.

LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.

出版信息

ACS Appl Mater Interfaces. 2021 Aug 4;13(30):35469-35483. doi: 10.1021/acsami.1c09121. Epub 2021 Jul 20.

DOI:10.1021/acsami.1c09121
PMID:34284573
Abstract

Osteoporosis therapies leveraging bisphosphonates and mineral components (e.g., magnesium, calcium, and strontium) have been raising attention because of their potential for managing this ever-growing disease. The administration of multicomponent therapeutics (combined therapy) in elderly patients is complex and suffers from low patient adherence. Herein, we report an all-in-one combination of four antiosteoporotic components into a new family of coordination complexes: [M(Halen)(HO)]·1.5HO [where M = Mg (), (MgCa) () and (MgCaSr) ()]. These solid-state complexes were prepared, for the first time, through microwave-assisted synthesis. It is demonstrated that the compounds are capable of releasing their antiosteoporotic components, both in conditions that mimic the path along the gastrointestinal tract and in long periods under physiological conditions (pH ∼7.4). More importantly, when administered in low concentrations, the compounds did not elicit a cytotoxic effect toward liver, kidney, and osteoblast-like cell lines. Besides, it is important to highlight the unique coordination complex with four bone therapeutic components, [(MgCaSr)(Halen)(HO)]·1.5HO (), which significantly promoted osteoblast metabolic activity up to ca. 1.4-fold versus the control group. These findings bring this type of compounds one-step closer to be considered as an all-in-one and more effective treatment for managing chronic bone diseases, prompting further research on their therapeutic properties.

摘要

利用双膦酸盐和矿物质成分(如镁、钙和锶)的骨质疏松症疗法因其在治疗这种日益增长的疾病方面的潜力而引起了关注。多组分治疗剂(联合治疗)在老年患者中的应用较为复杂,且患者依从性较低。在此,我们报告了将四种抗骨质疏松成分整合到一种新的配位化合物家族中:[M(Halen)(HO)]·1.5HO [其中 M = Mg (), (MgCa) () 和 (MgCaSr) ()]。这些固态配合物是首次通过微波辅助合成制备的。结果表明,这些化合物能够释放其抗骨质疏松成分,无论是在模拟胃肠道途径的条件下,还是在生理条件下(pH ∼7.4)长时间内。更重要的是,当以低浓度给药时,这些化合物对肝、肾和成骨样细胞系没有细胞毒性作用。此外,值得强调的是,具有四种骨治疗成分的独特配位化合物[(MgCaSr)(Halen)(HO)]·1.5HO ()显著促进成骨细胞代谢活性,与对照组相比约增加 1.4 倍。这些发现使这类化合物更接近被认为是一种更有效的治疗慢性骨病的综合治疗方法,并促使人们进一步研究其治疗特性。

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