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Cited by 55Advanced Drug Delivery SystemsNanoparticle-Based Drug DeliveryCholinesterase and Neurodegenerative Diseases

Combined Donepezil with Astaxanthin via Nanostructured Lipid Carriers Effective Delivery to Brain for Alzheimer’s Disease in Rat Model

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Shehata, Mustafa K, Ismail, Assem A, Kamel, Maher A·2023·International Journal of Nanomedicine
DOI 10.2147/ijn.s417928PMC PMC10391537
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Abstract

Introduction: Donepezil (DPL), a specific acetylcholinesterase inhibitor, is used as a first-line treatment to improve cognitive deficits in Alzheimer’s disease (AD) and it might have a disease modifying effect. Astaxanthin (AST) is a natural potent antioxidant with neuroprotective, anti-amyloidogenic, anti-apoptotic, and anti-inflammatory effects. This study aimed to prepare nanostructured lipid carriers (NLCs) co-loaded with donepezil and astaxanthin (DPL/AST–NLCs) and evaluate their in vivo efficacy in an AD-like rat model 30 days after daily intranasal administration. Methods: DPL/AST–NLCs were prepared using a hot high-shear homogenization technique, in vitro examined for their physicochemical parameters and in vivo evaluated. AD induction in rats was performed by aluminum chloride. The cortex and hippocampus were isolated from the brain of rats for biochemical testing and histopathological examination. Results: DPL/AST–NLCs showed z-average diameter 149.9 ± 3.21 nm, polydispersity index 0.224 ± 0.017, zeta potential – 33.7 ± 4.71 mV, entrapment efficiency 81.25 ± 1.98% (donepezil) and 93.85 ± 1.75% (astaxanthin), in vitro sustained release of both donepezil and astaxanthin for 24 h, spherical morphology by transmission electron microscopy, and they were stable at 4– 8 ± 2°C for six months. Differential scanning calorimetry revealed that donepezil and astaxanthin were molecularly dispersed in the NLC matrix in an amorphous state. The DPL/AST–NLC-treated rats showed significantly lower levels of nuclear factor-kappa B, malondialdehyde, β-site amyloid precursor protein cleaving enzyme-1, caspase-3, amyloid beta (Aβ 1‑42 ), and acetylcholinesterase, and significantly higher levels of glutathione and acetylcholine in the cortex and hippocampus than the AD-like untreated rats and that treated with donepezil–NLCs. DPL/AST–NLCs showed significantly higher anti-amyloidogenic, antioxidant, anti-acetylcholinesterase, anti-inflammatory, and anti-apoptotic effects, resulting in significant improvement in the cortical and hippocampal histopathology. Conclusion: Nose-to-brain delivery of DPL/AST–NLCs is a promising strategy for the management of AD. Keywords: Alzheimer’s disease, donepezil, astaxanthin, intranasal delivery, nanostructured lipid carriers

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Cited by

Sorted by citations

Authors
Shehata, M. K., Ismail, A. A., & Kamel, M. A.
Affiliations
Alexandria University (EG)
Corresponding author
Shehata, Mustafa K
ORCID
Venue
International Journal of Nanomedicine
Publisher
Informa UK Limited
Published
2023-07
Volume
Volume 18
Pages
4193-4227
ISSN
  • 1176-9114 (ISSN-L)
  • 1178-2013
DOI
10.2147/ijn.s417928
PMC
PMC10391537
OpenAlex
W4385267779
Cited by
55
References
8
Citations by year
2026: 21 · 2025: 20 · 2024: 12 · 2023: 2
FWCI
6.00
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Nanomedicine (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
Keywords
Alzheimer's disease, donepezil, astaxanthin, nanostructured lipid carriers, intranasal drug delivery, brain drug delivery, acetylcholinesterase inhibition, amyloid-beta, neuroinflammation, oxidative stress, apoptosis, neuroprotection, glutathione, acetylcholine, hippocampus
MeSH terms
Donepezil, Alzheimer Disease, Animals, Antioxidants, Brain, Drug Carriers, Lipids, Particle Size, Amyloid beta-Peptides, Xanthophylls, Nanostructures, Rats

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