Bone‐Targeting and Multishelled Oral Eldecalcitol Nanoparticles Improve Osteoporosis by Reconstruction of Osteogenic‐Osteoclastic Homeostasis

Author:

Meng Lingxiao12ORCID,Ma Wanli3,Jiang Yuping4,Li Xiaozhuang4,Zhang Minglei12,Yuan Rundong12,Fu Yaqiu12,Ma Haohua4,Lu Xiong5,Han Lu4,Liu Hongrui12,Li Minqi126ORCID

Affiliation:

1. Department of Bone Metabolism School and Hospital of Stomatology Cheeloo College of Medicine Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases Jinan 250000 China

2. Center of Osteoporosis and Bone Mineral Research Shandong University Jinan 250000 China

3. Department of Orthopedics The Second Hospital Cheeloo College of Medicine Shandong University Jinan 250033 China

4. Key Laboratory of Marine Drugs Ministry of Education School of Medicine and Pharmacy Ocean University of China Qingdao Shandong 266003 China

5. Institute of Biomedical Engineering College of Medicine Southwest Jiaotong University Chengdu Sichuan 610031 China

6. School of Clinical Medicine Jining Medical University Jining 272013 China

Abstract

AbstractCurrent treatment of postmenopausal osteoporosis (PMOP) focuses on systemic administration of medication, neglecting to proactively modulate the local microenvironment of skeletal system for superior therapeutic performance. Eldecalcitol (ED‐71), a novel drug for treating osteoporosis, still requires research to overcome high‐frequency delivery and low‐utilization. Here, a bone‐targeting and multishelled nanoparticles are developed for step‐wise release of ED‐71. The nanoparticles are achieved by using the chitosan/alginate outer layer as protective barrier against gastric acid, pectin middle layer as adhesive agent that improved intestinal penetration, and ethylene diamine tetraacetic acid‐grafted mesoporous silica nanomaterials core as bone‐targeting nanocarriers. After oral administration, the ED‐71‐loaded nanoparticles (ME‐ED‐71@PCA) promotes osteogenic differentiation of bone marrow mesenchymal stem cells by reducing intracellular oxidative stress, and inhibits the osteoclast differentiation. ME‐ED‐71@PCA improves bone mass in ovariectomized‐mice by promoting osteogenesis and inhibiting osteoclastogenesis, and the efficacy is more pronounced than ED‐71 alone. ME‐ED‐71@PCA exhibits satisfactory therapeutic performance due to its step‐wise drug release and bone‐targeting compared to ED‐71 administration, providing a new approach to re‐establish bone metabolic homeostasis in PMOP.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Shandong Province

Publisher

Wiley

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