Synthesis and characterization of hydroxy-bisphosphonate micrometer-sized particles by dispersion polymerization of a new styrylbisphosphonate monomer

Bisphosphonates (BPs) are nonhydrolyzable pyrophosphate (P-O-P) analogs possessing two phosphonate groups linked to a single carbon (P-C-P). The hydroxy-bisphosphonates (hydroxyBPs) are obtained when the hydroxy group is also linked to this bridging carbon. Their ability to form bidentate or tridentate chelates with calcium ions results in a high affinity to hydroxyapatite (HAP) in dentin, enamel and bones. In this study, we designed and prepared crosslinked poly(styrylbisphosphonate) (PStBP) micrometer-sized particles by dispersion polymerization of the styrylbisphosphonate (StBP) and ethylene glycol dimethacrylate (EDMA) monomers. The new StBP monomer was synthesized in an efficient one-pot synthesis using tris(trimethylsilyl)phosphite as the phosphorus source followed by methanolysis. The StBP monomer was successfully isolated and characterized as tri-sodium salt. Polymerization of the StBP monomer was carried out in two steps: in situ conversion of the tri-sodium StBP monomer back to its acid form, followed by radical dispersion polymerization in the presence of the crosslinker EDMA monomer. The resulting crosslinked PStBP micrometer-sized particles retained the unique high affinity of the hydroxy-bisphosphonate side groups to calcium ions and exhibited good adhesive properties to HAP.