Donepezil-loaded PLGA-b-PEG Nanoparticles Enhance the Learning and Memory Function of Beta-Amyloid Rat Model of Alzheimer's Disease.
Noro psikiyatri arsivi, cilt.59, sa.4, ss.281-289, 2022 (SCI-Expanded, Scopus, TRDizin)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 59 Sayı: 4
- Basım Tarihi: 2022
- Doi Numarası: 10.29399/npa.28275
- Dergi Adı: Noro psikiyatri arsivi
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CINAHL, EMBASE, Psycinfo, TR DİZİN (ULAKBİM)
- Sayfa Sayıları: ss.281-289
- İstanbul Üniversitesi-Cerrahpaşa Adresli: Evet
Özet
Introduction: Our aim is to reduce the side effects and increase the
efficiency of donepezil by formulating donepezil-loaded poly(lactic-coglycolic acid)-block-poly(ethylene glycol) nanoparticles (NPs) directly
targeting amyloid beta (Aβ) fibrils in the brain and evaluate behavioral
changes in this fibril model of AD.
Methods: AD model was developed by intracerebroventricular injection
of pre-aggregated β25-35 fibrils. Rats were intravenously administered
either solvent, donepezil-loaded NPs (15μg/kg) or free donepezil (1mg/
kg) 3 times for a week except for naïve controls. The effect of treatments
on anxiety, motor functions, and cognitive functions was tested by
elevated plus maze, locomotor activity, novel object recognition, and
Morris’s water maze tests, respectively.
Results: Accumulation of Aβ25-35 fibrils in brain sections was
confirmed. Anxiety-like behavior was observed in the Aβ Alzheimer and
free donepezil treatment groups while donepezil-loaded NP treatment
showed hypo-anxiety-like behavior. Donepezil-loaded NPs were
successful in treatment of short-term memory deficit better than free
donepezil injection. In Morris’s water maze, both donepezil-loaded NPs
and free donepezil groups found the platform in shorter time compared
to Aβ Alzheimer group. In locomotor activity test, both donepezil treated
groups moved less than the Aβ Alzheimer group and naïve controls.
After the pharmacological experiments, acetylcholinesterase activity was
determined and showed an increase in Aβ Alzheimer group compared
to controls. Donepezil-loaded NPs inhibited the acetylcholinesterase
activity more efficiently than the free donepezil group.
Conclusion: Targeting with donepezil-loaded PLGA-b-PEG-NPs
increases efficiency, helps to inhibit acetylcholinesterase activity more
substantially, improves cognitive decline due to its longer duration of
action and destabilizing effect on amyloid fibrils.