Electrosteric stealth Rivastigmine loaded liposomes for brain targeting: preparation, characterization, ex vivo, bio-distribution and in vivo pharmacokinetic studies
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Being one of the highly effective drugs in treatment of Alzheimer's disease, Rivastigmine brain targeting is highly demandable, therefore liposomal dispersion of Rivastigmine was prepared containing 2 mol% PEG-DSPE added to Lecithin, Didecyldimethyl ammonium bromide (DDAB), Tween 80 in 1:0.02:0.25 molar ratio. A major challenge during the preparation of liposomes is maintaining a stable formulation, therefore the aim of our study was to increase liposomal stability by addition of DDAB to give an electrostatic stability and PEG-DSPE to increase stability by steric hindrance, yielding what we called an electrosteric stealth (ESS) liposomes. A medium nano-sized liposome (478 ± 4.94 nm) with a nearly neutral zeta potential (ZP, -8 ± 0.2 mV) and an entrapment efficiency percentage of 48 ± 6.22 was prepared. Stability studies showed no major alteration after three months storage period concerning particle size, polydispersity index, ZP, entrapment efficiency and in vitro release study confirming the successful formation of a stable liposomes. No histopathological alteration was recorded for ESS liposomes of the sheep nasal mucosa. While ESS liposomes showed higher % of drug permeating through the sheep nasal mucosa (48.6%) than the drug solution (28.7%). On completing the in vivo pharmacokinetic studies of 36 rabbits showed 424.2% relative bioavailability of the mean plasma levels of the formula ESS compared to that of RHT intranasal solution and 486% relative bioavailability of the mean brain levels.
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Liposome-based strategy has demonstrated significant potential in enhancing the efficacy of approved drugs such as rivastigmine, galantamine, and donepezil for Alzheimer's disease treatment.
“This strategy has demonstrated significant potential in enhancing the efficacy of approved drugs such as rivastigmine, galantamine, and donepezil for the treatment of AD [70–73].”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [71]
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Recent Trends in Nano-Particulate Carriers for the Diagnosis and Treatment of Alzheimer’s Disease
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- Authors
- Nageeb El-Helaly, S., Abd Elbary, A., Kassem, M. A., & El-Nabarawi, M. A.
- Affiliations
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt
- Cairo University (EG)
- Venue
- Drug Delivery
- Publisher
- Informa UK Limited
- Published
- 2017-01-01
- Volume
- 24
- Issue
- 1
- Pages
- 692-700
- ISSN
- 1071-7544 (ISSN-L)
- 1521-0464
- PMC
- PMC8240971
- OpenAlex
- W2606003614
- Cited by
- 69
- References
- 49
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 13 · 2023: 12 · 2022: 8 · 2021: 5 · 2020: 9 · 2019: 3 · 2018: 6
- FWCI
- 1.77
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Drug Delivery (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Keywords
- rivastigmine, liposomes, brain targeting, Alzheimer's disease, DSPE-PEG, electrostatic stabilization, steric hindrance, liposome stability, nasal bioavailability, pharmacokinetics, brain drug levels, zeta potential
- MeSH terms
- Rivastigmine, Animals, Brain, Liposomes, Particle Size, Phosphatidylethanolamines, Polyethylene Glycols, Sheep
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