Effective improvement of the neuroprotective activity after spinal cord injury by synergistic effect of glucocorticoid with biodegradable amphipathic nanomicelles.
Dexamethasone acetate (DA) produces neuroprotective effects by inhibiting lipid peroxidation and inflammation by reducing cytokine release and expression. However, its clinical application is limited by its hydrophobicity, low biocompatibility and numerous side effects when using large dosage. Therefore, improving DA's water solubility, biocompatibility and reducing its side effects are important goals that will improve its clinical utility. The objective of this study is to use a biodegradable polymer as the delivery vehicle for DA to achieve the synergism between inhibiting lipid peroxidation and inflammation effects of the hydrophobic-loaded drugs and the amphipathic delivery vehicle. We successfully prepared DA-loaded polymeric micelles (DA/MPEG-PCL micelles) with monodispersed and approximately 25 nm in diameter, and released DA over an extended period in vitro. Additionally, in the hemisection spinal cord injury (SCI) model, DA micelles were more effective in promoting hindlimb functional recover, reducing glial scar and cyst formation in injured site, decreasing neuron lose and promoting axon regeneration. Therefore, our data suggest that DA/MPEG-PCL micelles have the potential to be applied clinically in SCI therapy.
a State Key Laboratory of Biotherapy and Cancer Center and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu , PR China.
YueLong
Y
Wang
b Department of Radiology, Huaxi MR Research Center (HMRRC), West China Hospital, Sichuan University , Chengdu , PR China.
Min
M
Wu
b Department of Radiology, Huaxi MR Research Center (HMRRC), West China Hospital, Sichuan University , Chengdu , PR China.
Lei
L
Gu
a State Key Laboratory of Biotherapy and Cancer Center and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu , PR China.
XiaoLing
X
Li
a State Key Laboratory of Biotherapy and Cancer Center and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu , PR China.
Jun
J
He
a State Key Laboratory of Biotherapy and Cancer Center and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu , PR China.
LiangXue
L
Zhou
a State Key Laboratory of Biotherapy and Cancer Center and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu , PR China.
Aiping
A
Tong
c National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , PR China , and.
Juan
J
Shi
d Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu , PR China.
HongYan
H
Zhu
a State Key Laboratory of Biotherapy and Cancer Center and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu , PR China.
JianGuo
J
Xu
a State Key Laboratory of Biotherapy and Cancer Center and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu , PR China.
Gang
G
Guo
D020341:Absorbable Implants; D000818:Animals; D004357:Drug Synergism; D005938:Glucocorticoids / Q000008:administration & dosage*; D008823:Micelles; D053758:Nanoparticles / Q000008:administration & dosage*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D016037:Single-Blind Method; D017550:Spectroscopy, Fourier Transform Infrared; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
D005938:Glucocorticoids; D008823:Micelles; D018696:Neuroprotective Agents
MPEG-PCL; Micelle; dexamethasone acetate; spinal cord injury; synergistic effect