Bone Targeting of Protein Drugs by Bisphosphonate Modification

摘要

For the treatment of bone diseases, targeteddelivery of protein drugs to the bone was examinedusing alendronate (ALN), a nitrogen-containingbisphosphonate, as a ligand for the bone.Approximately 2.1, 5.0 and 0.3 % of the doseaccumulated in the bone by 180 min after injection ofunmodified bovine serum albumin (BSA),recombinant mouse interferon-γ (IFN) andrecombinant human superoxide dismutase (SOD).On the other hand, approximately 9.5, 10.8 and10.3 % of the dose accumulated in the bone afterinjection of ALN-BSA, ALN-IFN and ALN-SOD,indicating that targeted delivery of proteins to thebone has been successfully achieved using the ALNmodification. Compared with unmodified SOD,ALN-SOD effectively suppressed the bonemetastasis in mice. These findings indicate that ALNmodification is a promising approach for targetingprotein drugs selectively to the bone.