Coordination Compounds As Multi-Delivery Systems for Osteoporosis

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: [M₂(H₄alen)₄(H₂O)₂]·1.5H₂O [where M²⁺ = Mg²⁺ (1), (Mg_0.535Ca_0.465)²⁺ (2) and (Mg_0.505Ca_0.450Sr_0.045)²⁺ (3)]. 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, [(Mg_0.505Ca_0.450Sr_0.045)₂(H₄alen)₄(H₂O)₂]·1.5H₂O (3), 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.

Keywords: bisphosphonates; controlled release; coordination compounds; osteoporosis; toxicological safety.