A Bone Targeting Nanoparticle Loaded OGP to Restore Bone Homeostasis for Osteoporosis Therapy

Abstract Restoring bone homeostasis is the key to the treatment of osteoporosis. How to increase osteogenic ability or inhibit osteoclast activity has always been a topic of great concern. In recent years, short peptides with biological activity have received great attention in bone repair. However, the application of short peptides is still limited due to the lack of a stable and targeted delivery system. Poly(lactic‐ co ‐glycolic acid) (PLGA) nanoparticles modified by alendronate (AL) to transport osteogenic peptides (OGP) (AL‐PLGA@P NPs) are designed. Benefiting from the high affinity of AL for hydroxyapatite, AL‐PLGA@P NPs have the ability to target bone. In this delivery system, OGP that promotes osteogenesis synergizes with AL, which inhibits osteoclasts, to regulate bone homeostasis, which gives them more advantages in the treatment of osteoporosis. The data shows that nanoparticles can selectively deliver peptides to the bone surface without systemic toxicity. Moreover, nanoparticles can upregulate osteogenesis‐related factors (ALP, Runx‐2, and BMP2) and downregulate osteoclast‐related factors (TRAP and CTSK) in vitro. With AL‐PLGA@P NPs, bone microarchitecture and bone mass are improved in ovariectomized osteoporosis rats. Therefore, this study proposes a novel osteoporosis‐based drug system that effectively improves bone density.