TY - JOUR
T1 - Bone-targeting liposome formulation of Salvianic acid A accelerates the healing of delayed fracture Union in Mice
AU - Liu, Yanzhi
AU - Jia, Zhenshan
AU - Akhter, Mohammed P.
AU - Gao, Xiang
AU - Wang, Xiaobei
AU - Wang, Xiaoyan
AU - Zhao, Gang
AU - Wei, Xin
AU - Zhou, You
AU - Wang, Xiuli
AU - Hartman, Curtis W.
AU - Fehringer, Edward V.
AU - Cui, Liao
AU - Wang, Dong
N1 - Funding Information:
This work was supported in part by the National Natural Science Foundation, China [grant numbers 81273518, 81703584], Guangdong Province Natural Science Foundation, China [grant number 2017A030310614], National Institute of Health, United States [grant number R01AR062680], and the University of Nebraska Medical Center College of Pharmacy. YL, ZJ, LC and DW are co-inventors of a patent application on this technology. The other coauthors declare no conflict of interests regarding the publication of this article.
PY - 2018/10
Y1 - 2018/10
N2 - 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.
AB - 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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U2 - 10.1016/j.nano.2018.07.011
DO - 10.1016/j.nano.2018.07.011
M3 - Article
C2 - 30076934
AN - SCOPUS:85051681034
VL - 14
SP - 2271
EP - 2282
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
SN - 1549-9634
IS - 7
ER -