Galantamine nanoparticles outperform oral galantamine in an Alzheimer's rat model: pharmacokinetics and pharmacodynamics.
Samar O El-GanainyMennatallah A GowayedPassant MohamedMarwa BelalAmira Sayed HanafyPublished in: Nanomedicine (London, England) (2021)
Aim: Galantamine is an acetylcholinesterase inhibitor frequently used in Alzheimer's disease management. Its cholinergic adverse effects and rapid elimination limit its therapeutic outcomes. We investigated the pharmacodynamics and pharmacokinetics of 2-week intranasal galantamine-bound chitosan nanoparticles (G-NP) treatment in scopolamine-induced Alzheimer's disease rat model. Materials & methods: Behavioral, neurobiochemical and histopathological changes were assessed and compared with oral and nasal solutions. Brain uptake and pharmacokinetics were determined using a novel validated LC/MS assay. Results: G-NP enhanced spatial memory, exploring behavior and cholinergic transmission in rats. Beta-amyloid deposition and Notch signaling were suppressed and the histopathological degeneration was restored. G-NP potentiated galantamine brain delivery and delayed its elimination. Conclusion: G-NP hold promising therapeutic potentials and brain targeting, outperforming conventional galantamine therapy.
Keyphrases
- resting state
- white matter
- cognitive decline
- functional connectivity
- cerebral ischemia
- drug delivery
- type diabetes
- clinical trial
- adipose tissue
- multiple sclerosis
- metabolic syndrome
- oxidative stress
- skeletal muscle
- cancer therapy
- mesenchymal stem cells
- bone marrow
- high glucose
- drug induced
- mild cognitive impairment
- mass spectrometry
- atomic force microscopy
- high resolution
- smoking cessation
- placebo controlled
- wound healing
- weight loss
- double blind