Back to Journals » International Journal of Nanomedicine » Volume 12

PEG-b-(PELG-g-PLL) nanoparticles as TNF-α nanocarriers: potential cerebral ischemia/reperfusion injury therapeutic applications

Authors Xu G, Gu H, Hu B, Tong F, Liu D, Yu X, Zheng Y, Gu J

Received 21 December 2016

Accepted for publication 3 March 2017

Published 23 March 2017 Volume 2017:12 Pages 2243—2254

DOI https://doi.org/10.2147/IJN.S130842

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Alexander Kharlamov

Peer reviewer comments 3

Editor who approved publication: Dr Lei Yang


Guangtao Xu,1,2 Huan Gu,1,3 Bo Hu,4 Fei Tong,2 Daojun Liu,1 Xiaojun Yu,1 Yongxia Zheng,1,2 Jiang Gu1

1Department of Pathology and Chemistry, Provincial Key Laboratory of Infectious Diseases and Immunopathology, Collaborative and Creative Center, Molecular Diagnosis and Personalized Medicine, Shantou University Medical College, Shantou, Guangdong, 2Department of Pathology, Provincial Key Discipline of Pharmacology, Jiaxing University Medical College, Jiaxing, Zhejiang, People’s Republic of China; 3Department of Physics, University of Maryland, College Park, Annapolis, MD, USA; 4Department of Chemical Pathology, Jiaxing Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Jiaxing, Zhejiang, People’s Republic of China

Abstract: Brain ischemia/reperfusion (I/R) injury (BI/RI) is a leading cause of death and disability worldwide. However, the outcome of pharmacotherapy for BI/RI remains unsatisfactory. Innovative approaches for enhancing drug sensitivity and recovering neuronal activity in BI/RI treatment are urgently needed. The purpose of this study was to evaluate the protective effects of tumor necrosis factor (TNF)-α-loaded poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(l-lysine)) (TNF-α/PEG-b-(PELG-g-PLL)) nanoparticles on BI/RI. The particle size of PEG-b-(PELG-g-PLL) and the loading and release rates of TNF-α were determined. The nanoparticle cytotoxicity was evaluated in vitro using rat cortical neurons. Sprague Dawley rats were preconditioned with free TNF-α or TNF-α/PEG-b-(PELG-g-PLL) polyplexes and then subjected to 2 hours ischemia and 22 hours reperfusion. Brain edema was assessed using the brain edema ratio, and the antioxidative activity was assessed by measuring the superoxide dismutase (SOD) activity and the malondialdehyde (MDA) content in the brain tissue. We further estimated the inflammatory activity and apoptosis level by determining the levels of interleukin-4 (IL-4), IL-6, IL-8, IL-10, and nitric oxide (NO), as well as the expression of glial fibrillary acidic protein (GFAP), intercellular adhesion molecule-1 (ICAM-1), and cysteine aspartase-3 (caspase-3), in the brain tissue. We provide evidence that TNF-α preconditioning attenuated the oxidative stress injury, the inflammatory activity, and the apoptosis level in I/R-induced cerebral injury, while the application of block copolymer PEG-b-(PELG-g-PLL) as a potential TNF-α nanocarrier with sustained release significantly enhanced the bioavailability of TNF-α. We propose that the block copolymer PEG-b-(PELG-g-PLL) may function as a potent nanocarrier for augmenting BI/RI pharmacotherapy, with unprecedented clinical benefits. Further studies are needed to better clarify the underlying mechanisms.

Keywords: PEG-b-(PELG-g-PLL), TNF-α, ischemia/reperfusion, brain

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]