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Zonisamide-loaded triblock copolymer nanomicelles as a novel drug delivery system for the treatment of acute spinal cord injury

Authors Li JL, Deng JJ, Yuan JX, Fu J, Li XL, Tong AP, Wang YL, Chen YM, Guo G

Received 25 November 2016

Accepted for publication 11 February 2017

Published 29 March 2017 Volume 2017:12 Pages 2443—2456

DOI https://doi.org/10.2147/IJN.S128705

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Lakshmi Kiran Chelluri

Peer reviewer comments 3

Editor who approved publication: Dr Linlin Sun

JingLun Li,1 JiaoJiao Deng,2 JinXian Yuan,1 Jie Fu,1 XiaoLing Li,2 AiPing Tong,2 YueLong Wang,2 YangMei Chen,1 Gang Guo2

1Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 2State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, People’s Republic of China

Abstract: Spinal cord injury (SCI) commonly leads to lifelong disability due to the limited regenerative capacity of the adult central nervous system. Nanomicelles can be used as therapeutic systems to provide effective treatments for SCI. In this study, a novel triblock monomethyl poly(ethylene glycol)-poly(L-lactide)-poly(trimethylene carbonate) copolymer was successfully synthesized. Next, polymeric nanomicelles loaded with zonisamide (ZNS), a Food and Drug Administration-approved antiepileptic drug, were prepared and characterized. The ZNS-loaded micelles (ZNS-M) were further utilized for the treatment of SCI in vitro and in vivo. The obtained ZNS-M were ~50 nm in diameter with good solubility and dispersibility. Additionally, these controlled-release micelles showed significant antioxidative and neuron-protective effects in vitro. Finally, our results indicated that ZNS-M treatment could promote motor function recovery and could increase neuron and axon density in a hemisection SCI model. In summary, these results may provide an experimental basis for the use of ZNS-M as a clinically applicable therapeutic drug for the treatment of SCI in the future.

Keywords: spinal cord injury, zonisamide, nanomicelles

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