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-2(H(4)alen)(4)(H2O)(2)]center dot 1.5H(2)O [where M2+ = Mg2+ (1), (Mg0.535Ca0.465)(2+) (2) and (Mg0.505Ca0.450Sr0.045)(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 similar to 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, [(Mg0.505Ca0.450Sr0.045)(2)(H(4)alen)(4)(H2O)(2)]center dot 1.5H(2)O (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
BONE-MINERAL DENSITY; CALCIUM SUPPLEMENTATION; STRONTIUM RANELATE; BISPHOSPHONATE; NANOPARTICLES; EPIDEMIOLOGY; PREVENTION; EFFICACY
subject category
Nanoscience & Nanotechnology; Materials Science, Multidisciplinary
authors
Barbosa, JS; Pinto, M; Barreiro, S; Fernandes, C; Mendes, RF; Lavrador, P; Gaspar, VM; Mano, JF; Borges, F; Remiao, F; Braga, SS; Paz, FAA
our authors
Filipe Alexandre Almeida Paz
Principal Researcher
Jéssica Barbosa
PhD Student
João Mano
Full professor
Pedro Lavrador
PhD Student
Ricardo Faria Mendes
Junior Researcher
Vítor Gaspar
Assistant ProfessorProjects
CICECO - Aveiro Institute of Materials (UIDB/50011/2020)
acknowledgements
Thanks are due to the University of Aveiro and Foundation for Science and Technology/MCTES for the financial support for the associated laboratory LAQV-REQUIMTE (project reference UIDB/50006/2020), to CICECO-Aveiro Institute of Materials (UIDB/50011/2020 and UIDP/50011/2020) and CIQUP (UIDB/00081/2020), through national founds and, where applicable, cofinanced by the FEDER, within the PT2020 Partnership Agreement. The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project No. 022161 (cofinanced by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). The work was further supported by UIDB/04378/2020 with funding from FCT/MCTES through national funds.