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.
| Language | English (US) |
|---|---|
| Pages | 2271-2282 |
| Number of pages | 12 |
| Journal | Nanomedicine: Nanotechnology, Biology, and Medicine |
| Volume | 14 |
| Issue number | 7 |
| DOIs | |
| State | Published - Oct 1 2018 |
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All Science Journal Classification (ASJC) codes
- Bioengineering
- Medicine (miscellaneous)
- Molecular Medicine
- Biomedical Engineering
- Materials Science(all)
- Pharmaceutical Science
Cite this
Bone-targeting liposome formulation of Salvianic acid A accelerates the healing of delayed fracture Union in Mice. / 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.
In: Nanomedicine: Nanotechnology, Biology, and Medicine, Vol. 14, No. 7, 01.10.2018, p. 2271-2282.Research output: Contribution to journal › Article
}
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
PY - 2018/10/1
Y1 - 2018/10/1
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.
UR - http://www.scopus.com/inward/record.url?scp=85051681034&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85051681034&partnerID=8YFLogxK
U2 - 10.1016/j.nano.2018.07.011
DO - 10.1016/j.nano.2018.07.011
M3 - Article
VL - 14
SP - 2271
EP - 2282
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
T2 - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
SN - 1549-9634
IS - 7
ER -