Curcumin-loaded polymersomes ameliorated cognitive dysfunction

A dual brain-targeting curcumin-loaded polymersomes ameliorated cognitive dysfunction in intrahippocampal amyloid-β1–42-injected mice


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Authors Jia TT, Sun ZG, Lu Y, Gao J, Zou H, Xie FY, Zhang GQ, Xu H, Sun DX, Yu Y, Zhong YQ

Received 17 August 2015

Accepted for publication 14 March 2016

Published 5 August 2016 Volume 2016:11 Pages 3765—3775

DOI https://dx.doi.org/10.2147/IJN.S94622

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Xian Xu

Peer reviewer comments 4

Editor who approved publication: Dr Lei Yang


Tingting Jia,1,* Zhiguo Sun,1,* Ying Lu,1 Jie Gao,1 Hao Zou,1 Fangyuan Xie,2 Guoqing Zhang,2 Hao Xu,3Duxin Sun,3 Yuan Yu,1 Yanqiang Zhong1

1Department of Pharmaceutical Sciences, School of Pharmacy, The Second Military Medical University,2Department of Pharmacy, Eastern Hepatobiliary Surgery Hospital, Shanghai, People’s Republic of China; 3Department of Pharmaceutical Sciences, School of Pharmacy, University of Michigan, Ann Arbor, MI, USA

*These authors contributed equally to this work

Abstract:

Due to the impermeability of the blood–brain barrier and the nonselective distribution of drugs in the brain, the therapeutic access to intractable neurological disorders is challenging. In this study, dual brain-targeting polymersomes (POs) functionalized by transferrin and Tet-1 peptide (Tf/Tet-1-POs) promoted the transportation of curcumin into the brain and provided neuroprotection. The modification of the ligands that bind to the surface of POs was revealed by X-ray photoelectron spectroscopy analysis. The cell uptake of a coculture model of mouse brain capillary endothelial cells with neurons showed that the Tf/Tet-1-POs had significant transportation properties and possessed affinity for neurons. The pharmacokinetic analysis showed that the blood–brain barrier permeability–surface efficiency of the Tf/Tet-1-POs was 0.28 mL/h/g and that the brain tissue uptake rate (% ID/g) was 0.08, which were significant compared with the controls (P<0.05). The curcumin-encapsulated Tf/Tet-1-POs provided neuroprotection and ameliorated cognitive dysfunction in intrahippocampal amyloid-β1–42-injected mice. These results suggest that the dual brain-targeting POs are more capable of drug delivery to the brain that can be exploited as a multiple noninvasive vehicle for targeting therapeutics.

Keywords: polymersomes, transferrin, Tet-1 peptide, Alzheimer’s disease



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