Edaravone-Encapsulated Agonistic Micelles Rescue Ischemic Brain Tissue by Tuning Blood-Brain Barrier Permeability

Jin, Qu; Cai, Yu; Li, Sihan; Liu, Haoran; Zhou, Xingyu; Lu, Chunqiang; Gao, Xihui; Qian, Jun; Zhang, Jun; Ju, Shenghong; Li, Cong

doi:10.7150/thno.18219

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Theranostics 2017; 7(4):884-898. doi:10.7150/thno.18219 This issue Cite

Research Paper

Edaravone-Encapsulated Agonistic Micelles Rescue Ischemic Brain Tissue by Tuning Blood-Brain Barrier Permeability

Qu Jin^1*, Yu Cai^2*, Sihan Li¹, Haoran Liu¹, Xingyu Zhou¹, Chunqiang Lu², Xihui Gao¹, Jun Qian¹, Jun Zhang³, Shenghong Ju^2✉, Cong Li^1✉

1. Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, P. R. China.
2. Jiangsu Key Laboratory of Molecular and Functional Imaging Department of Radiology, Zhongda Hospital, Medical School of Southeast University, 87 Dingjiaqiao Road, Nanjing 210009, P. R. China.
3. Department of Radiology, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai 200041, P. R. China.
*These authors share equal first authorship.

Citation:

Jin Q, Cai Y, Li S, Liu H, Zhou X, Lu C, Gao X, Qian J, Zhang J, Ju S, Li C. Edaravone-Encapsulated Agonistic Micelles Rescue Ischemic Brain Tissue by Tuning Blood-Brain Barrier Permeability. Theranostics 2017; 7(4):884-898. doi:10.7150/thno.18219. https://www.thno.org/v07p0884.htm

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Abstract

Thrombolysis has been a standard treatment for ischemic stroke. However, only 2-7% patients benefit from it because the thrombolytic agent has to be injected within 4.5 h after the onset of symptoms to avoid the increasing risk of intracerebral hemorrhage. As the only clinically approved neuroprotective drug, edaravone (EDV) rescues ischemic brain tissues by eradicating over-produced reactive oxygen species (ROS) without the limitation of therapeutic time-window. However, EDV's short circulation half-life and inadequate cerebral uptake attenuate its therapeutic efficacy. Here we developed an EDV-encapsulated agonistic micelle (EDV-AM) to specifically deliver EDV into brain ischemia by actively tuning blood-brain barrier (BBB) permeability. The EDV-AM actively up-regulated endothelial monolayer permeability in vitro. HPLC studies showed that EDV-AM delivered more EDV into brain ischemia than free EDV after intravenous injection. Magnetic resonance imaging also demonstrated that EDV-AM more rapidly salvaged ischemic tissue than free EDV. Diffusion tensor imaging indicated the highest efficiency of EDV-AM in accelerating axonal remodeling in the ipsilesional white matter and improving functional behaviors of ischemic stroke models. The agonistic micelle holds promise to improve the therapeutic efficiency of ischemic stroke patients who miss the thrombolytic treatment.

Keywords: ischemic stroke, blood-brain-barrier, neuroprotective therapy, agonistic micelle, edaravone.

Citation styles

APA

Jin, Q., Cai, Y., Li, S., Liu, H., Zhou, X., Lu, C., Gao, X., Qian, J., Zhang, J., Ju, S., Li, C. (2017). Edaravone-Encapsulated Agonistic Micelles Rescue Ischemic Brain Tissue by Tuning Blood-Brain Barrier Permeability. Theranostics, 7(4), 884-898. https://doi.org/10.7150/thno.18219.

ACS

Jin, Q.; Cai, Y.; Li, S.; Liu, H.; Zhou, X.; Lu, C.; Gao, X.; Qian, J.; Zhang, J.; Ju, S.; Li, C. Edaravone-Encapsulated Agonistic Micelles Rescue Ischemic Brain Tissue by Tuning Blood-Brain Barrier Permeability. Theranostics 2017, 7 (4), 884-898. DOI: 10.7150/thno.18219.

NLM

CSE

Jin Q, Cai Y, Li S, Liu H, Zhou X, Lu C, Gao X, Qian J, Zhang J, Ju S, Li C. 2017. Edaravone-Encapsulated Agonistic Micelles Rescue Ischemic Brain Tissue by Tuning Blood-Brain Barrier Permeability. Theranostics. 7(4):884-898.

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