Synthesis of Phosphonated Polyphosphazenes via Two Synthetic Routes

Phosphonate and phosphonic acid containing polymers are of interest for bone tissue engineering because these species have the ability to bind hydroxyapatite [Ca10(PO4)6(OH)2], which comprises 70 wt % of bone. The synthesis of phosphoester [−PO(OEt)2] and phosphonic acid [−PO(OH)2] functionalized polyphosphazenes is described. These polymers could mimic the natural bone healing mechanism, making them excellent candidates for implantable bone grafts. Two synthetic protocols have been developed to obtain the polymers, herein referred to as prior- and post-side-group assembly. Prior assembly required the synthesis of a phosphonate-containing side group before attachment to the polyphosphazene backbone through nucleophilic substitution, whereas post-assembly required the synthesis of a polyphosphazene containing free amino groups to which the phosphonate can be coupled by Michael addition after polymer synthesis. The final step for both routes required the deprotection of the phosphoester to the corresponding phosphonic acid. The polymers were characterized by 1H and 31P NMR, GPC, and DSC techniques. A six week hydrolysis study using phosphate buffered saline (PBS) determined their hydrolytic sensitivity. All the polymers were hydrolytically sensitive, as required for this purpose, and decomposed ∼2–50% by week six. The hydrolysis products were analyzed by UV–vis techniques, and their release was monitored over the course of the experiment. These results are in agreement with percent solid mass loss data. In general, all the phosphonic acid polymers hydrolyzed at a faster rate than their corresponding phosphoester derivatives.