Title : Alendronate functionalized bone-targeting pomolic acid liposomes restore bone homeostasis for osteoporosis treatment
Abstract:
Osteoporosis, characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation, severely affects elderly health. Currently, there are no effective treatments, highlighting the need for new therapies. Salvia miltiorrhiza Bunge, a traditional Chinese medicine, has long been used for bone disorders, but its active compounds and mechanisms are not fully understood. This study identified five potential active compounds from 186 Salvia miltiorrhiza components using network pharmacology, with Pomolic acid showing the strongest effect in the TRAP assay. Molecular docking suggested Pomolic acid targets the MAPK/NF-κB pathways. In vitro, it inhibited RANKL-induced osteoclastogenesis and bone resorption, reduced osteoclast-related gene expression, and suppressed MAPK/NF-κB activation. In vivo, Pomolic acid prevented ovariectomy-induced bone loss in mice. However, its poor solubility and lack of targeting limit its application. To address this, we developed a bone-targeting nanomedicine (PA@TLipo) that encapsulates Pomolic acid in alendronate-functionalized liposomes. PA@TLipo was synthesized, purified, encapsulated, and labeled. In vitro and in vivo experiments confirmed its cytotoxicity, bone-targeting, and anti-osteoporosis effects. PA@TLipo accumulated in bone tissue, reduced bone loss, improved bone targeting, and reduced systemic toxicity. It also inhibited osteoclast formation and bone resorption in vitro and reduced bone loss in ovariectomy-induced osteoporotic mice. This study presents a novel, effective therapeutic solution for osteoporosis.
