Construction puerarin-based framework as a bone-targeted and pH-responsive nanomedicine for osteoporosis treatment

Osteoporosis (OP) is a degenerative bone disease that commonly occurs in elderly people. It often manifests in bone pain and increased risk of fractures, significantly impacting the quality of life for middle-aged and elderly individuals. Several anti-osteoporosis drugs are currently available in clinical practice, their long-term use has shown limited efficacy and potential complications. The natural compound puerarin (Pue) has demonstrated to be promising for OP treatment via regulating osteoclast and osteoblast differentiation. However, its poor solubility, low bioavailability, and lack of bone-targeting severely impeded its clinical applications. To address the above issues, we reported herein the synthesis of Pue-based framework (HCCP-Pue-PEG-ALN, HPPA NPs) via conjugation of Pue, NH₂-PEG, and alendronic acid (ALN) using hexachlorocyclotriphosphazene (HCCP) as the linkage. We demonstrated that the HPPA NPs display the features, including high water dispersibility, pH responsive drug release, low cytotoxicity, bone targeting feature, and positive effects on both osteoclasts and osteoblasts. Therefore, we believe this idea reported in this work will be of great interest in design natural compounds-based drug delivery systems and promotes clinic translation of natural compounds for OP treatment.