Water/pH dual responsive in situ calcium supplement collaborates simvastatin for osteoblast promotion mediated osteoporosis therapy via oral medication

Abstract

Calcium supplement is the most commonly adopted treatment for osteoporosis but usually requires high dose and frequency. The modality of calcium supplement is therefore overlooked by current nanomedicine-based osteoporosis therapies without proper oral formulations. Herein, we proposed a tetracycline (Tc) modified and monostearin (MS) coated amorphous calcium carbonate (ACC) platform (TMA) as oral bone targeted and osteoporosis microenvironment (water/pH) responsive carrier for in situ calcium supplement. Moreover, current osteoporosis therapies also fall short of finding suitable molecular target and effective therapeutic regimen to further increase the therapeutic efficacy over available treatment means. As a result, the simvastatin (Sim) was loaded into TMA to construct drug delivery system (TMA/Sim) capable of synergistically activating the bone morphogenetic proteins (BMPs)-Smad pathway to provide a novel therapeutic regimen for osteoblast promotion mediated osteoporosis therapy. Our results revealed that optimized TMA showed high accessibility and oral availability with targeted drug delivery to bone tissue. Most importantly, benefit from the effective in situ calcium supplement and targeted Sim delivery, this therapeutic regime (TMA/Sim) achieved better synergetic effects than conventional combination strategies with promising osteoporosis reversion performance under low calcium dosage (1/10 of commercial calcium carbonate tablet) and significantly attenuated side effects.