Sodium alginate and naloxone loaded macrophage-derived nanovesicles for the treatment of spinal cord injury  

作　　者：Xiaoyao Liu Xue Jiang Qi Yua Wenwen Shen He Tian Xifan Mei Chao Wu 

机构地区：[1]Pharmacy School,Jinzhou Medical University,Jinzhou 121001,China [2]Department of Orthopedics,The First Affiliated Hospital of Jinzhou Medical University,Jinzhou 121004,China [3]Department of Histology and Embryology,Jinzhou Medical University,Jinzhou 121001,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2022年第1期87-101,共15页亚洲药物制剂科学（英文）

基　　金：the financial support received from the Natural Science Foundation of Liaoning Province [No. 20180550155, 2021-MS-332];the National Natural Science Foundation of China (No.81671907, 81871556, 82072165);LiaoNing Revitalization Talents Program (No. XLYC1902108);Scientific Research Project of the Educational Department of Liaoning Province(No. JYTQN201917, JYTQN201919);Liaoning Provincial Key Laboratory of Marine Bioactive Substances and Technological Innovation Center of Liaoning Pharmaceutical Action and Quality Evaluation (No. 2020–10)。

摘　　要：Spinal cord injury(SCI)causes Ca^(2+) overload,which can lead to inflammation and neuronal apoptosis.In this study,we prepared a nanovesicle derived from macrophage membrane(MVs),which encapsulated sodium alginate(SA)and naloxone(NAL)to inhibit inflammation and protect neurons by reducing the free Ca^(2+) concentration at the SCI site.Based on the transmission electron microscopy(TEM)image,the encapsulated sample(NAL–SA–MVs)had a particle size of approximately 134±11 nm and exhibited a sustained release effect.The encapsulation rate of NAL and SA was 82.07%±3.27%and 72.13%±2.61%in NAL–SA–MVs,respectively.Targeting tests showed that the NAL–SA–MVs could accumulate in large quantities and enhance the concentration of SA and NAL at the lesion sites.In vivo and in vitro studies indicated that the NAL–SA–MVs could decrease the concentration of free Ca^(2+),which should further alleviate the inflammatory response and neuronal apoptosis.Anti-inflammation results demonstrated that the NAL–SA–MVs could reduce the pro-inflammation factors(iNOS,TNF-α,IL-1β,IL-6)and increase the expression of antiinflammation factors(IL-10)at the cell and animal level.Concurrently,fluorescence,flow cytometry and western blot characterization showed that the apoptotic condition of the neurons was significantly inhibited.In addition,the motor function of C57 mice were significantly improved after NAL–SA–MVs treatment.In conclusion,it is suggested that the NAL–SA–MVs has tremendous potential in the treatment of SCI.

关 键 词：NALOXONE Sodium alginate Spinal cord injury Macrophage membrane INFLAMMATION NEUROPROTECTION 

分 类 号：R943[医药卫生—药剂学] R965[医药卫生—药学]