Facile fabrication of phosphazene-quercetin-alendronate composites as pH-responsive bone-targeted nanomedicine for osteoporosis treatment

Osteoporosis, closely related to age, is characterized by impaired bone mass and bone strength, damage of bone microstructure, resulting in a higher risk of fractures with minimal trauma, especially in the hip and spine. Quercetin (Que), a natural compound, has previously demonstrated its potential anti-osteoporosis effects via promoting bone formation and anti-bone resorption. However, Que is poor water solubility, lack of bone targeting, and requires high concentration to exert its therapeutic effects. In this work, a pH-responsive and bone-targeted nanomedicine HCCP-Que-PEG-ALN (HQPA) was developed via using hexachlorocyclotriphosphazene (HCCP) as the cross-linkage, Que, alendronate (ALN), and amino-polyethylene glycol (NH2-PEG) as other building blocks. We demonstrated that HQPA can form spherical nanoparticles in aqueous solution with average size of 158.3 ± 59.8 nm with high drug loading capacity of Que (31.4 w/w%) and obvious bone-targeting capability. in vitro experimental results indicated that HQPA NPs have dual anti-osteoporosis effects of promoting osteoblasts and inhibiting osteoclasts. Furthermore, HQPA NPs can effectively reduce the bone loss in OVX mice with low toxicity to major organs. We believe that this method should be a general and useful route for fabrication of bone-targeted natural-compounds-based nanomedicines for treatment different bone-related diseases.