Targeted Delivery of Curcumin to Polyethylene-Induced Osteolysis by Magnetically Guided Zoledronate-Anchored Poly Lactic-Co-Glycolic Acid Nanoparticles via Repressing NF-κB Signaling.

Jingyi Li,Qiqi Xing,Zhen Zhang,Senbo An,Chengcheng Niu,Yihe Hu,Qi Guo,Zichao Jiang,Yixiao Pan,Long Wang

doi:10.3389/fphar.2020.600156

Abstract

Aseptic loosening induced by periprosthetic osteolysis (PPO) is the leading complication of total joint arthroplasty (TJA) and results in patients having to receive revision surgery. However, there is still no efficient drug to prevent or even slow the pathological process. Herein, we report novel dual-targeted, curcumin-loaded Poly lactic-co-glycolic acid nanoparticles (ZSCNPs) to inhibit polyethylene-induced osteolysis. These ZSCNPs have good biocompatibility and excellent bone binding affinity. Under external magnetic field guidance, the ZSCNPs can specifically target osteolytic sites with sustained curcumin release, efficiently suppress the effect of IκB kinase, subsequently inhibit activation of the nuclear factor-kappa B (NF-κB) signaling pathway, and ultimately prevent osteoclast formation and particle-induced osteolysis. Therefore, these novel dual-targeted, drug-loaded nanoparticles could be applied as a useful strategy for targeted treatment of PPO after TJA.

Highlights

Despite the huge clinical success of total joint arthroplasty (TJA), TJA complications, such as periprosthetic osteolysis (PPO) and infection, often lead to TJA failure and cause great pain to patients
Far, there is no effective drug for clinical treatment of PPO due to Magnetically Guided Zoledronate-Anchored Poly lacticco-glycolic acid (PLGA) Nanoparticles the involvement of multiple inflammatory factors in the pathological process of PPO (Termaat et al, 2005; Goodship et al, 2008)
On the basis of our previous research, we found that the incidence of PPO is closely related to the receptor activator of NFκB (RANK)/receptor activator of NF-κB ligand (RANKL)/ osteoprotegerin system, and the RANKL/OPG ratio in PPO is significantly increased (Wang et al, 2016)

Summary

INTRODUCTION

Despite the huge clinical success of total joint arthroplasty (TJA), TJA complications, such as periprosthetic osteolysis (PPO) and infection, often lead to TJA failure and cause great pain to patients. It is highly desirable to design a zoledronate- and SPIO-anchored PLGA to efficiently deliver curcumin to the site of PPO under an external magnetic field. Our group verified that curcumin can inhibit the entire NF-κB activation process by inhibiting the effect of IKK, preventing polyethylene (PE)-induced osteolysis and bone loss, and repressing the RANK/c-Fos/nuclear factor of activated T cells cytoplasmic 1 (NFATc1) signaling pathway (An et al, 2018). We report magnetically targeted, zoledronate-anchored, dual-targeted, drug-loaded nanoparticles (ZSCNPs) for treatment of PEinduced osteolysis under an external magnetic field and the mechanism (Figure 1). Because of the wonderful bone binding affinity, efficient sustained curcumin release in osteolytic lesions and obvious inhibition of OC formation and particle-induced osteolysis, these novel dual-targeted drug-loaded NPs have potential for targeted treatment of PPO after TJA

MATERIALS AND METHODS

AND DISCUSSION

CONCLUSION

Findings

ETHICS STATEMENT