scholarly journals Osthole-Loaded Nanoemulsion Enhances Brain Target in the Treatment of Alzheimer’s Disease via Intranasal Administration

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Yilei Song ◽  
Xiangyu Wang ◽  
Xingrong Wang ◽  
Jianze Wang ◽  
Qiulian Hao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Polyethylene Glycol ◽  
Water Solubility ◽  
Oral Absorption ◽  
Ethyl Oleate ◽  
Brain Targeting ◽  
Intravenous Route ◽  
Diagram Method ◽  
Nasal Route

Osthole (OST) is a natural coumarin compound that exerts multiple pharmacologic effects. However, the poor water solubility and the low oral absorption of OST limit its clinical application for the treatment of neurologic diseases. A suitable preparation needs to be tailored to evade these unfavourable properties of OST. In this study, an OST nanoemulsion (OST-NE) was fabricated according to the pseudoternary phase diagram method, which was generally used to optimize the prescription in light of the solubility of OST in surfactants and cosurfactants. The final composition of OST-NE was 3.6% of ethyl oleate as oil phase, 11.4% of the surfactant (polyethylene glycol ester of 15-hydroxystearic acid: polyoxyethylene 35 castor oil = 1 : 1 ), 3% of polyethylene glycol 400 as cosurfactant, and 82% of the aqueous phase. The pharmacokinetic study of OST-NE showed that the brain-targeting coefficient of OST was larger by the nasal route than that by the intravenous route. Moreover, OST-NE inhibited cell death, decreased the apoptosis-related proteins (Bax and caspase-3), and enhanced the activity of antioxidant enzymes (superoxide dismutase and glutathione) in L-glutamate-induced SH-SY5Y cells. OST-NE improved the spatial memory ability, increased the acetylcholine content in the cerebral cortex, and decreased the activity of acetylcholinesterase in the hippocampus of Alzheimer’s disease model mice. In conclusion, this study indicates that the bioavailability of OST was improved by using the OST-NE via the nasal route. A low dose of OST-NE maintained the neuroprotective effects of OST, such as inhibiting apoptosis and oxidative stress and regulating the cholinergic system. Therefore, OST-NE can be used as a possible alternative to improve its bioavailability in the prevention and treatment of Alzheimer’s disease.

scholarly journals Repurposing ibuprofen-loaded microemulsion for the management of Alzheimer’s disease: evidence of potential intranasal brain targeting

Drug Delivery ◽  
2021 ◽  
Vol 28 (1) ◽  
pp. 1188-1203
Author(s):  
Ming Ming Wen ◽  
Noha Ismail Khamis Ismail ◽  
Maha M. A. Nasra ◽  
Amal Hassan El-Kamel
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Targeting

New advances in brain-targeting nano-drug delivery systems for Alzheimer's disease

2021 ◽  
pp. 1-67
Author(s):  
Qin Ouyang ◽  
Yingcai Meng ◽  
Wenhu Zhou ◽  
Jianbin Tong ◽  
Zeneng Cheng ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Drug Delivery ◽  
Alzheimer's Disease ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Brain Targeting ◽  
Nano Drug Delivery

scholarly journals Brain targeting of 9c,11t-Conjugated Linoleic Acid, a natural calpain inhibitor, preserves memory and reduces Aβ and P25 accumulation in 5XFAD mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Orli Binyamin ◽  
Keren Nitzan ◽  
Kati Frid ◽  
Yael Ungar ◽  
Hanna Rosenmann ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Linoleic Acid ◽  
Neurodegenerative Diseases ◽  
Conjugated Linoleic Acid ◽  
Brain Targeting ◽  
Calpain Inhibitor ◽  
Term Administration ◽  
5Xfad Mice

AbstractDeregulation of Cyclin-dependent kinase 5 (CDK5) by binding to the activated calpain product p25, is associated with the onset of neurodegenerative diseases, such as Alzheimer’s disease (AD). Conjugated Linoleic Acid (CLA), a calpain inhibitor, is a metabolite of Punicic Acid (PA), the main component of Pomegranate seed oil (PSO). We have shown recently that long-term administration of Nano-PSO, a nanodroplet formulation of PSO, delays mitochondrial damage and disease advance in a mouse model of genetic Creutzfeldt Jacob disease (CJD). In this project, we first demonstrated that treatment of mice with Nano-PSO, but not with natural PSO, results in the accumulation of CLA in their brains. Next, we tested the cognitive, biochemical and pathological effects of long-term administration of Nano-PSO to 5XFAD mice, modeling for Alzheimer’s disease. We show that Nano-PSO treatment prevented age-related cognitive deterioration and mitochondrial oxidative damage in 5XFAD mice. Also, brains of the Nano-PSO treated mice presented reduced accumulation of Aβ and of p25, a calpain product, and increased expression of COX IV-1, a key mitochondrial enzyme. We conclude that administration of Nano-PSO results in the brain targeting of CLA, and suggest that this treatment may prevent/delay the onset of neurodegenerative diseases, such as AD and CJD.

Intranasal delivery of nanoparticle encapsulated tarenflurbil: A potential brain targeting strategy for Alzheimer's disease

2016 ◽  
Vol 92 ◽  
pp. 224-234 ◽  
Author(s):  
Eameema Muntimadugu ◽  
Raju Dhommati ◽  
Anjali Jain ◽  
Venu Gopala Swami Challa ◽  
M. Shaheen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Targeting ◽  
Intranasal Delivery ◽  
Targeting Strategy

scholarly journals Multiple-Coated PLGA Nanoparticles Loading Triptolide Attenuate Injury of a Cellular Model of Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Lu Jia ◽  
Xiao-qi Nie ◽  
Hong-ming Ji ◽  
Zhi-xiang Yuan ◽  
Rong-shan Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Chinese Herb ◽  
Amyloid Β ◽  
Eutectic Mixture ◽  
Neuroprotective Activity ◽  
Brain Targeting ◽  
Cellular Model ◽  
Model Of Alzheimer’S Disease ◽  
Chitosan Hydrochloride

Alzheimer’s disease (AD) is the most common neurodegenerative disease, which is associated with extracellular deposition of amyloid-β proteins (Aβ). It has been reported that triptolide (TP), an immunosuppressive and anti-inflammatory agent extracted from a Chinese herb Tripterygium wilfordii, shows potential neuroprotective effects pertinent to AD. However, the clinical use of TP for AD could be hampered due to its high toxicity, instability, poor water solubility, and nonspecific biodistribution after administration. In this paper, we reported a kind of multiple-coated PLGA nanoparticle with the entrapment of TP and surface coated by chitosan hydrochloride, Tween-80, PEG20000, and borneol/mentholum eutectic mixture (MC-PLGA-TP-NP) as a novel nasal brain targeting preparation for the first time. The obtained MC-PLGA-TP-NP was 147.5 ± 20.7  nm with PDI of 0.263 ± 0.075 , zeta potential of 14.62 ± 2.47  mV, and the entrapment efficiency and loading efficiency of 93.14 % ± 4.75 % and 1.17 ± 0.08 % , respectively. In comparison of TP, MC-PLGA-TP-NP showed sustained-release profile and better transcellular permeability to Caco-2 cells in vitro. In addition, our data showed that MC-PLGA-TP-NP remarkably reduced the cytotoxicity, attenuated the oxidative stress, and inhibited the increase of the intracellular Ca2+ influx in differentiated PC12 cells induced by Aβ1-42. Therefore, it can be concluded that MC-PLGA-TP-NP is a promising preparation of TP, which exerts a better neuroprotective activity in the AD cellular model.

Gamma radiation preparation of chitosan nanoparticles for controlled delivery of memantine

2019 ◽  
Vol 34 (8) ◽  
pp. 1150-1162 ◽  
Author(s):  
Rasha R Radwan ◽  
Ashraf M Abdel Ghaffar ◽  
Hussein E Ali
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gamma Radiation ◽  
Histopathological Examination ◽  
Chitosan Nanoparticles ◽  
Amyloid Β ◽  
Brain Targeting ◽  
Morris Water Maze Test ◽  
Infrared Analysis ◽  
Amyloid Β Peptide

The purpose of the current study is to prepare chitosan nanoparticles by gamma radiation as a new brain delivery system for memantine to improve its therapeutic efficiency. Fourier-transform infrared analysis of chitosan nanoparticles showed the characteristic peaks of chitosan and the reduction of particle size induced by irradiation at doses 10, 20 and 30 kGy. The solubility of chitosan nanoparticles was tested using different solvents and exhibited good solubility in both water and 1% acetic acid than other tested solvents at 80°C. Different formulations containing memantine -loaded chitosan nanoparticles were evaluated for brain targeting on aluminum-induced Alzheimer’s disease in rats. Memory deficit was evaluated using the Morris water maze test. The levels of amyloid-β peptide, tumour necrosis factor alpha, interleukin-1β and interleukin-6 in brain tissues as well as the serum level of brain-derived neurotrophic factor were assayed. Data demonstrated that memantine -loaded chitosan nanoparticles 1:1 transported memantine effectively into the brain compared to free memantine as evidenced by better behaviour performance and biochemical amelioration and confirmed by histopathological examination in Alzheimer’s disease rats. Interestingly, the therapeutic effect of memantine -loaded chitosan nanoparticles 1:1 was superior to memantine -loaded chitosan nanoparticles 1:2 and memantine -loaded chitosan nanoparticles 2:1. Based on these findings, it is reasonable to suggest that memantine -loaded chitosan nanoparticles 1:1 could be a promising approach for Alzheimer’s disease.

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