Metal amino-bisphosphonates: Mapping of their controlled release features as drug delivery systems of anti-osteoporosis drugs
Maria Vassaki, Christina Kotoula, and Konstantinos D. Demadis
Crystal Engineering Growth and Design Laboratory, Department of Chemistry, University of Crete, Heraklion, Greecea
Bis-phosphonates (BPs), known also as “-dronates”, constitute a class of drugs that are used to mitigate bone-related diseases, such as osteoporosis. The amino-BPs (N-BPs), containing a N atom in their backbone, are the most active phosphonate-type anti-osteoporosis drugs and they are coined “2nd and 3rd generation” BP drugs. Furthermore, these BPs by virtue of their phosphonate groups could also act as organic ligands/linkers that have an extraordinary capacity to coordinate with virtually any metal ion of the Periodic Table. As a result, a wide variety of coordination polymers and (less commonly) complexes can be synthesized. Their determined crystal structures have shown that there exist mononuclear or binuclear complexes (0D) and coordination networks with different structural motifs (1D, 2D or 3D).
In this work, we focus on the synthesis and characterization of new metal-drug (drug = N-BPs) hybrid materials that are constructed by coordination of amino-BPs with biocompatible alkaline-earth metal cations (specifically Ca²⁺ and Sr²⁺). In addition, we report the fabrication MOF-containing tablets and we evaluate their ability to release the active BP drug under specific (acidic) conditions that mimic the human stomach. Based on structure-activity relationships which were mapped out, one might envision designing Drug Delivery Systems (DDS) based on these MOFs, depending on the individual patients’ needs in order to achieve an effective therapy with decreased side effects.
Keywords: Bisphosphonate Drugs, Osteoporosis, metal-hybrid materials, Drug Delivery Systems.