Site-activatable targeting of macromolecular alendronate for accelerated fracture healing

Abstract

ABSTRACTSustainable social activity is a major goal in an aging society, although this is limited by loss of athleticism, with osteoporosis-related fractures being the most common cause of long-term behavioral restrictions in older people. Therefore, the development of therapeutics that shorten the duration of fracture therapy is essential to improve the quality of life and social activity of older individuals. In this study, we developed a polyethylene glycol-modified alendronate (PEG-ALN) that can efficiently deliver the active ingredient (ALN) to fracture sites. PEG-ALN released ALN in response to an acidic pH and was systemically administered to mice in a fracture model. PEG-ALN exhibited selective accumulation at the fracture site and significantly accelerated bone healing compared to free ALN. This study highlights the utility of a simple polymer modification of ALN as a systemically injectable medicine for patients with bone fractures.

Keywords

• Bone fracture
• alendronate
• osteoporosis
• PEGylated drug
• osteoclast