Hydroxybisphosphonate‐containing polymeric drug‐delivery systems designed for targeting into bone tissue

The preparation and characterization of a novel polymeric drug‐delivery system designed for bone targeting of antineoplastics is described. The system was based on biocompatible poly[ N ‐(2‐hydroxypropyl)methacrylamide] carrier containing hydroxybisphosphonate targeting moieties and the model radiotherapeutics 125 I or 111 In or the anticancer drug doxorubicin. The in vitro binding studies with hydroxyapatite as a bone model proved that the system was efficiently adsorbed on this mineral. The systems contained model drugs bound by stable (amide), hydrolytically cleavable (hydrazone) or enzymatically cleavable (Gly‐Phe‐Leu‐Gly tetrapeptide) spacers. It was proven in vitro that, in the case of cleavable spacers, the drug could be released from the polymer carrier at a rate depending on the pH or enzymatic stimulus.