The hydrothermal reaction between bioactive metals (Ca2+, Zn2+, and Mg2+) salts and clinically utilized bisphosphonates (BPs), alendronate (ALEN) and zoledronate (ZOLE), promotes the formation of several materials denominated as bisphosphonate-based biocompatible coordination complexes (pBioCCs). The systematic exploration of the effect of three variables M2+/BP molar ratio, temperature, and pH on the reaction yielded an unprecedented number of materials of enough crystal quality for structural elucidation (ALEN-Ca forms I and II, ALEN-Mg, ALEN-Zn forms I and II, ZOLE-Ca forms I and II, ZOLE-Mg, forms I and II, and ZOLE-Zn forms I and II). Crystal structures were unveiled by single X-ray diffraction at 100 K and solid-state properties were revealed by thermogravimetry, vibrational spectroscopy, and elemental analysis. The elemental analysis along with Raman spectra initially evidenced the formation of pBioCCs. Comparison of the thermograms between the BP ligand and the pBioCCs demonstrated higher thermal stability of these materials. The dissolution of pBioCCs was tested and contrasted to that of the commercially employed generic form of alendronate (Fosamax®) and zoledronate (Zometa®). Quantification by UV-Vis spectroscopy of the ALEN content from the pBioCCs was performed by derivatization with Cu2+, whereas the release of ZOLE was directly quantified. A phase inversion temperature (PIT) nano-emulsion method was applied to the synthesis of ALEN-Ca form II and ZOLE-Ca form I. Size distribution analysis demonstrated the efficiency of this method to decrease the particle size of the pBioCCs (from ~60 µm to ~438 d.nm). The cytotoxicity of ALEN, ALEN-Ca form II (bulk and nanocrystals) against the MDA-MB-231 cell line was investigated. Nano-ALEN-Ca form II presents higher cytotoxicity than ALEN and ALEN-Ca form II (bulk crystals). These results provide evidence of the structure, stability, dissolution and cytotoxicity of ALEN- and ZOLE-based pBioCCs and pave the way for better formulation strategies for these drugs to treat bone-related diseases.

Potentiating bisphosphonate-based coordination complexes to treat osteolytic metastases

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.