A Bone‐Penetrating Precise Controllable Drug Release System Enables Localized Treatment of Osteoporotic Fracture Prevention via Modulating Osteoblast‐Osteoclast Communication

Abstract

Improving local bone mineral density (BMD) at fracture‐prone sites of bone is a clinical concern for osteoporotic fracture prevention. In this study, a featured radial extracorporeal shock wave (rESW) responsive nano‐drug delivery system (NDDS) is developed for local treatment. Based on a mechanic simulation, a sequence of hollow zoledronic acid (ZOL)‐contained nanoparticles (HZNs) with controllable shell thickness that predicts various mechanical responsive properties is constructed by controlling the deposition time of ZOL and Ca2+ on liposome templates. Attributed to the controllable shell thickness, the fragmentation of HZNs and the release of ZOL and Ca2+ can be precisely controlled with the intervention of rESW. Furthermore, the distinct effect of HZNs with different shell thicknesses on bone metabolism after fragmentation is verified. In vitro co‐culture experiments demonstrate that although HZN2 does not have the strongest osteoclasts inhibitory effect, the best pro‐osteoblasts mineralization results are achieved via maintaining osteoblast‐osteoclast (OB‐OC) communication. In vivo, the HZN2 group also shows the strongest local BMD enhancement after rESW intervention and significantly improves bone‐related parameters and mechanical properties in the ovariectomy (OVX)‐induced osteoporosis (OP) rats. These findings suggest that an adjustable and precise rESW‐responsive NDDS can effectively improve local BMD in OP therapy.

Enhanced Adsorption Stability and Biofunction Durability with Phosphonate-Grafted, PEGylated Copolymer on Hydroxyapatite Surface

“…22 Bisphosphonate drugs (e.g., zoledronic acid) used clinically to treat osteoporosis and bone tumors are known to capture Ca 2+ and Mg 2+ ions. 23 Also, the organophosphate monolayer has been reported to be easily prepared through self-assembly on metal oxide surfaces. 24 Moreover, it is worth noting that phosphate and phosphonic acid compounds exhibit favorable biosafety and biocompatibility.…”

“…It is known that the PO 3 groups in organophosphorus form strong covalent bonds with Ca 2+ , which owns a higher association constant compared to the ligand bond formed between ND groups and Ca 2+ . Bisphosphonate drugs (e.g., zoledronic acid) used clinically to treat osteoporosis and bone tumors are known to capture Ca 2+ and Mg 2+ ions . Also, the organophosphate monolayer has been reported to be easily prepared through self-assembly on metal oxide surfaces .…”