Bone-targeting liposome formulation of Salvianic acid A accelerates the healing of delayed fracture Union in Mice |
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| Authors: | Yanzhi Liu Zhenshan Jia Mohammed P Akhter Xiang Gao Xiaobei Wang Xiaoyan Wang Gang Zhao Xin Wei You Zhou Xiuli Wang Curtis W Hartman Edward V Fehringer Liao Cui Dong Wang |
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| Institution: | 1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA;2. Guangdong Key laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong, China;3. Osteoporosis Research Center, Creighton University, Omaha, NE, USA;4. Stem Cell research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China;5. Department of Orthopaedic Surgery and Rehabilitation, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA;6. Columbus Community Hospital Orthopedics & Sports Medicine Clinic, Columbus, NE, USA |
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| Abstract: | 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. |
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| Keywords: | Salvianic acid A Fracture Bone-targeting Liposome Delayed fracture union |
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