Bone-targeting liposome formulation of Salvianic acid A accelerates the healing of delayed fracture Union in Mice

• Published in: Nanomedicine 2018-10, Vol.14 (7), p.2271-2282
• Main Authors: Liu, Yanzhi, Jia, Zhenshan, Akhter, Mohammed P., Gao, Xiang, Wang, Xiaobei, Wang, Xiaoyan, Zhao, Gang, Wei, Xin, Zhou, You, Wang, Xiuli, Hartman, Curtis W., Fehringer, Edward V., Cui, Liao, Wang, Dong
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - toxicity; Bone-targeting; Caffeic Acids - chemistry; Caffeic Acids - pharmacology; Cholesterol - metabolism; Delayed fracture union; Disease Models, Animal; Drug Compounding; Female; Fracture; Fracture Healing - drug effects; Fractures, Bone - chemically induced; Fractures, Bone - drug therapy; Lactates - chemistry; Lactates - pharmacology; Liposome; Liposomes - administration & dosage; Liposomes - chemistry; Mice; Osteogenesis; Prednisone - toxicity; Proton Pump Inhibitors - chemistry; Proton Pump Inhibitors - pharmacology; Salvianic acid A
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2018.07.011

Delayed fracture union is a significant clinical challenge in orthopedic practice. There are few non-surgical therapeutic options for this pathology. To address this challenge, we have developed a bone-targeting liposome (BTL) formulation of salvianic acid A (SAA), a potent bone anabolic agent, for improved treatment of delayed fracture union. Using pyrophosphorylated cholesterol as the targeting ligand, the liposome formulation (SAA-BTL) has demonstrated strong affinity to hydroxyapatite in vitro, and to bones in vivo. Locally administered SAA-BTL was found to significantly improve fracture callus formation and micro-architecture with accelerated mineralization rate in callus when compared to the dose equivalent SAA, non-targeting SAA liposome (SAA-NTL) or no treatment on a prednisone-induced delayed fracture union mouse model. Biomechanical analyses further validated the potent therapeutic efficacy of SAA-BTL. These results support SAA-BTL formulation, as a promising therapeutic candidate, to be further developed into an effective and safe clinical treatment for delayed bone fracture union. Salvianic acid A (SAA), a potent bone anabolic agent, was encapsulated in a bone-targeting liposome formulation (BTL), bearing pyrophosphorylated cholesterol as a novel targeting ligand. Locally administered SAA-BTL at the fracture site of a delayed union mouse model found the formulation markedly improve fracture callus micro-architecture and mechanical strength with significantly accelerated healing time. [Display omitted]