Neuroprotective Effects of Engineered Polymeric Nasal Microspheres Containing Hydroxypropyl-β-cyclodextrin on β-Amyloid (1-42)-Induced Toxicity
Abstract
β-Amyloid (Aβ) plaques are the key neurotoxic assemblies in Alzheimer disease. It has been suggested that an interaction occurs between membrane cholesterol and Aβ aggregation in the brain. Cyclodextrins can remove cholesterol from cell membranes and change receptor function. This study aimed to investigate the effect of hydroxypropyl-β-cyclodextrin (HP-CD) polymeric microspheres, based on chitosan or sodium alginate, on the levels of lipid peroxidation, reactive oxygen species production, and mitochondrial function in brain synaptosomes. The effect of microspheres on DNA fragmentation, the expression of Bcl-2, Bax, and Apex1 mRNAs in rat hippocampus after Aβ(1-42) peptide-induced neurotoxicity was also evaluated. Comparison with HP-CD raw material was performed. Aβ(1-42) treatment significantly decreased the mitochondrial activity of Apex1 and Bcl-2 mRNAs, induced DNA fragmentation, and increased mRNA levels of Bax. Treatment with HP-CD microspheres against Aβ(1-42) significantly reduced DNA fragmentation and increased the Bcl-2/Bax mRNA ratio and mitochondrial function. In addition, HP-CD microspheres used against Aβ(1-42) decreased the levels of lipid peroxidation and reactive oxygen species production. These results indicate that nasally administered spray-dried HP-CD microspheres are able to provide protection against Aβ(1-42)-induced neurotoxicity, due to the suppressed levels of oxidative stress and apoptotic signals in the rat hippocampus.
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Nasal administration of drugs using the nose-to-brain pathway allows direct drug targeting into the brain, avoiding the first-pass effect and bypassing the BBB.
“The nasal administration of drugs using the nose-to-brain pathway allows direct drug targeting into the brain, avoiding the first-pass effect and bypassing the BBB.”
From Nanoemulsions for “Nose-to-Brain” Drug Delivery (2019) · cites this paper as [16]
Nose-to-brain drug delivery is a painless, non-invasive administration route that can deliver therapeutic agents into the brain by bypassing the blood-brain barrier.
“Nose-to-brain drug delivery is a painless, non-invasive administration route that can be used to deliver therapeutic agents into the brain by bypassing the BBB [10,14,15,16,17].”
From Nanoemulsions for “Nose-to-Brain” Drug Delivery (2019) · cites this paper as [16]
Cyclodextrins can be used for the preparation of formulations able to cross the blood-brain barrier, administered through nasal or oral/parenteral routes.
“For instance, it is known that cyclodextrins can be used for the preparation of formulations able to cross the BBB, administered through nasal or oral/parenteral routes [16,23,80,81].”
From Nanoemulsions for “Nose-to-Brain” Drug Delivery (2019) · cites this paper as [16]
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References 68 · Cited by 37
- Authors
- Yalcin, A., Soddu, E., Turunc Bayrakdar, E., Uyanikgil, Y., Kanit, L., Armagan, G., Rassu, G., Gavini, E., & Giunchedi, P.
- Affiliations
- University of Sassari (IT)
- Corresponding author
- Gavini, Elisabetta
- Venue
- Journal of Pharmaceutical Sciences
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 105
- Issue
- 8
- Pages
- 2372-2380
- ISSN
- 0022-3549 (ISSN-L)
- OpenAlex
- W2473297513
- Cited by
- 37
- References
- 68
- Citations by year
- 2025: 6 · 2024: 3 · 2023: 6 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 1
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmaceutical Sciences (publishedVersion)
- PubMed (publishedVersion)
- UnissResearch (Università degli Studi di Sassari) (submittedVersion)
- Funders
- Ege University Research Foundation (12/ECZ/037)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- hydroxypropyl-β-cyclodextrin, polymer microspheres, amyloid-beta 42, Alzheimer's disease, neuroprotection, intranasal drug delivery, chitosan, sodium alginate, oxidative stress, lipid peroxidation, reactive oxygen species, mitochondrial function, DNA fragmentation, apoptosis, Bcl-2, Bax, APEX1, hippocampus, membrane cholesterol
- MeSH terms
- 2-Hydroxypropyl-beta-cyclodextrin, Administration, Intranasal, Animals, Hippocampus, Microspheres, Peptide Fragments, Synaptosomes, Lipid Peroxidation, Amyloid beta-Peptides, Rats, Sprague-Dawley, Neuroprotective Agents, Neurotoxicity Syndromes, DNA Fragmentation
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