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Antidepressant effects of curcumin and HU-211 coencapsulated solid lipid nanoparticles against corticosterone-induced cellular and animal models of major depression

Authors He XL, Zhu YJ, Wang M, Jing GX, Zhu RR, Wang SL

Received 24 March 2016

Accepted for publication 12 July 2016

Published 3 October 2016 Volume 2016:11 Pages 4975—4990

DOI https://doi.org/10.2147/IJN.S109088

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Lei Yang


Xiaolie He,* Yanjing Zhu,* Mei Wang, Guoxin Jing, Rongrong Zhu, Shilong Wang

Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Abstract:
Major depression is a complex neuropsychiatric disorder with few treatment approaches. The use of nontargeted antidepressants induced many side effects with their low efficacy. A more precise targeting strategy is to develop nanotechnology-based drug delivery systems; hence, we employed solid lipid nanoparticles (SLNs) to encapsulate HU-211 and curcumin (Cur). The antidepressant effects of the dual-drug nanoparticles (Cur/SLNs-HU-211) for major depression treatment were investigated in corticosterone-induced cellular and animal models of major depression. Cur/SLNs-HU-211 can effectively protect PC12 cells from corticosterone-induced apoptosis and can release more dopamine, which may be associated with the higher uptake of Cur/SLNs-HU-211 shown by cellular uptake behavior analysis. Additionally, Cur/SLNs-HU-211 significantly reduced the immobility time in forced swim test, enhanced fall latency in rotarod test, and improved the level of dopamine in mice blood. Cur/SLNs-HU-211 can deliver more Cur to the brain and thus produce a significant increase in neurotransmitters level in brain tissue, especially in the hippocampus and striatum. The results of Western blot and immunofluorescence revealed that Cur/SLNs-HU-211 can significantly enhance the expression of CB1, p-MEK1, and p-ERK1/2. Our study suggests that Cur/SLNs-HU-211 may have great potential for major depression treatment.

Keywords: major depression, curcumin, HU-211, solid lipid nanoparticles, dopamine

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