Periostin-targeted SDSSD peptide decorated calcium phosphate nanocomposites incorporation with simvastatin for osteoporosis treatment

• Published in: Nanotechnology Vol. 35; no. 7; pp. 75102 - 75113
• Main Authors: Pan, Zian, Zhang, Zhen, Deng, Xiongwei, Hu, Fanqi, Jia, Fan, Lu, Jianqing, Zhang, Xuesong, Yang, Xiaoqing, Gao, Yujuan, Wang, Xuan, Cui, Xinyue, Xu, Chenlu, Wu, Yan
• Format: Journal Article
• Language: English
• Published: IOP Publishing 12.02.2024
• Subjects: bone-targeted; calcium phosphate; nano delivery system; osteoporosis treatment; simvastatin
• ISSN: 0957-4484; 1361-6528
• DOI: 10.1088/1361-6528/ad0dc9

Abstract The limited options of anabolic drugs restrict their application potential in osteoporosis treatment, despite their theoretical superiority in therapeutic efficacy over antiresorptive drugs. As a prevailing strategy, nano-delivery systems could offer a wider choice of anabolic drugs. In this study, calcium phosphate nanocomposites incorporated with simvastatin (Sim) with periostin-targeting ability were designed and prepared for osteoporosis treatment. Carboxymethyl dextran (CMD) as an anionic and hydrophilic dextran derivative was used to stabilize CaP. In addition, periosteum-targeted peptide (SDSSD) was further grafted on CMD to achieve the bone targeting function. In a one-step coordination assembly strategy, hydrophobic anabolic agent Sim and SDSSD-CMD graft (SDSSD-CMD) were incorporated into the CaP nanoparticles forming SDSSD@CaP/Sim nanocomposites. The resulting SDSSD@CaP/Sim possesses uniform size, great short-term stability and excellent biocompatibility. Moreover, SDSSD@CaP/Sim exhibited a reduced release rate of Sim and showed slow-release behaviour. As anticipated, the nanocomposites exhibited bone bonding capacity in both cellular and animal studies. Besides, SDSSD@CaP/Sim achieved obviously enhanced osteoporosis treatment effect compared to direct injection of Sim in vivo . Therefore, our findings highlight the potential of SDSSD-incorporated and CaP-based nanocomposites as a viable strategy to enhance the therapeutic efficacy of anabolic drugs for osteoporosis treatment.