Bone-targeting polyphosphodiesters that promote osteoblastic differentiation

Polymers for pharmaceutical use have been attractive in medical treatments because of the conjugation of multifunctional components and their long circulation time in the blood stream. Bone-targeted drug delivery systems are also no exceptional, and several polymers have been proposed for the treatment of bone diseases, such as cancer metastasis and osteoporosis. Herein, we report that polyphosphodiesters (PPDEs) have a potential to enhance osteoblastic differentiation, and they have a targeting ability to bone tissues in vivo. Two types of PPDEs, poly (ethylene sodium phosphate) (PEP center dot Na) and poly (propylene sodium phosphate) (PPP center dot Na), have been synthesized. Regardless of the alkylene structure in the main chain of PPDEs, the gene expression of osteoblast-specific transcription factors and differentiation markers of mouse osteoblastic-like cells (MC3T3-E1 cells) cultured in a differentiation medium was significantly upregulated by the addition of PPDEs. Moreover, it was also clarified that the signaling pathway related to cytoplasmic calcium ions was activated by PPDEs. The mineralization of MC3T3-E1 cells has a similar trend with its gene expression and is synergistically enhanced by PPDEs with beta-glycerophosphate. The biodistribution of fluorescence-labeled PPDEs was also determined after intravenous injection in mice. PPDEs accumulated well in the bone through the blood stream, whereas polyphosphotriesters (PPTEs) tended to be excreted from the kidneys. Hydrophilic PEP center dot Na showed a superior bone affinity as compared with PPP center dot Na. PPDEs could be candidate polymers for the restoration of bone remodeling and bone-targeting drug delivery platforms.

Automated summary

This article reports the potential of polyphosphodiesters (PPDEs) to enhance osteoblastic differentiation and target bone tissues in vivo. Two types of PPDEs, poly (ethylene sodium phosphate) (PEP center dot Na) and poly (propylene sodium phosphate) (PPP center dot Na), have been synthesized and shown to upregulate the gene expression of osteoblast-specific transcription factors in mouse osteoblastic-like cells. The mineralization of these cells is also enhanced by PPDEs with beta-glycerophosphate.