Neuroprotective Potential of Curcumin-Loaded Nanostructured Lipid Carrier in an Animal Model of Alzheimer’s Disease: Behavioral and Biochemical Evidence

Article type: Research Article

Authors: Sadegh Malvajerd, Soroor^a | Izadi, Zhila^b | Azadi, Amir^c | Kurd, Masoumeh^d | Derakhshankhah, Hossein^b | Sharifzadeh, Mohammad^e | Akbari Javar, Hamid^{f; g; *} | Hamidi, Mehrdad^{d; h; *}

Affiliations: [a] Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran | [b] Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran | [c] Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran | [d] Zanjan Pharmaceutical Nanotechnology Research Center (ZPNRC), Department of Pharmaceutical Nanotechnology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran | [e] Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran | [f] Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran | [g] Tehran Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran | [h] Department of Pharmaceutics, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran

Correspondence: [*] Correspondence to: Mehrdad Hamidi and Hamid Akbari Javar, (Mehrdad Hamidi) Zanjan Pharmaceutical Nanotechnology Research Center (ZPNRC), Department of Pharmaceutical Nanotechnology, School of Pharmacy, Zanjan University of Medical Sciences, 45139-56184 Zanjan; (Hamid Akbari Javar) Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. (Mehrdad Hamidi) E-mail: [email protected]., (Hamid Akbari Javar) E-mail: [email protected].

Abstract:  Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases and is caused by accumulation of amyloid-β (Aβ) peptide and is associated with neurological abnormalities in learning and memory. The protective role of curcumin on nerve cells, along with a potent antioxidant and free radical scavenging activity, has been widely studied. However, its low bioavailability and limited transport ability across the blood-brain barrier are two major drawbacks of its application in the treatment of different neurodegenerative diseases. The present study was designed to improve the effectiveness of curcumin in the treatment of Aβ-induced cognitive deficiencies in a rat model of AD by loading it into nanostructured lipid carriers (NLCs). The accumulation rate of curcumin (505.76±38.4 ng/g–1 h) in rat brain, as well as its serum levels, were significantly increased by using curcumin-loaded NLCs. The effective role of NLCs for brain delivery of curcumin was confirmed by reduced oxidative stress parameters (ROS formation, lipid peroxidation, and ADP/ATP ratio) in the hippocampal tissue and improvement of spatial memory. Also, histopathological studies revealed the potential of Cur–NLCs in decreasing the hallmarks of Aβ in AD in the animal model. The result of studying the neuroprotective potential of Cur-NLC in both pre-treatment and treatment modes showed that loading curcumin in NLCs is an effective strategy for increasing curcumin delivery to the brain and reducing Aβ-induced neurological abnormalities and memory defects and that it can be the basis for further studies in the area of AD prevention and treatment.

Keywords: Alzheimer’s disease, amyloid-β protein, blood-brain barrier, curcumin, nanostructured lipid carriers, neurodegeneration

DOI: 10.3233/JAD-190083

Journal: Journal of Alzheimer's Disease, vol. 69, no. 3, pp. 671-686, 2019