Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer's disease

Manal Fouad Ismail,1 Aliaa Nabil ElMeshad,2 Neveen Abdel-Hameed Salem31Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 3Department of Narcotics and Ergogenic Ai...

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Autores principales: Ismail MF, ElMeshad AN, Salem NA
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Publicado: Dove Medical Press 2013
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spelling oai:doaj.org-article:0a5cad646838461589e4243bc5515cea2021-12-02T05:14:22ZPotential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer's disease1176-91141178-2013https://doaj.org/article/0a5cad646838461589e4243bc5515cea2013-01-01T00:00:00Zhttp://www.dovepress.com/potential-therapeutic-effect-of-nanobased-formulation-of-rivastigmine--a12045https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Manal Fouad Ismail,1 Aliaa Nabil ElMeshad,2 Neveen Abdel-Hameed Salem31Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 3Department of Narcotics and Ergogenic Aids and Poisons, National Research Center, Giza, EgyptBackground: To sustain the effect of rivastigmine, a hydrophilic cholinesterase inhibitor, nanobased formulations were prepared. The efficacy of the prepared rivastigmine liposomes (RLs) in comparison to rivastigmine solution (RS) was assessed in an aluminium chloride (AlCl3)-induced Alzheimer’s model.Methods: Liposomes were prepared by lipid hydration (F1) and heating (F2) methods. Rats were treated with either RS or RLs (1 mg/kg/day) concomitantly with AlCl3 (50 mg/kg/day).Results: The study showed that the F1 method produced smaller liposomes (67.51 ± 14.2 nm) than F2 (528.7 ± 15.5 nm), but both entrapped the same amount of the drug (92.1% ± 1.4%). After 6 hours, 74.2% ± 1.5% and 60.8% ± 2.3% of rivastigmine were released from F1 and F2, respectively. Both RLs and RS improved the deterioration of spatial memory induced by AlCl3, with RLs having a superior effect. Further biochemical measurements proved that RS and RLs were able to lower plasma C-reactive protein, homocysteine and asymmetric dimethylarginine levels. RS significantly attenuated acetylcholinesterase (AChE) activity, whereas Na+/K+-adenosine triphosphatase (ATPase) activity was enhanced compared to the AlCl3-treated animals; however, RLs succeeded in normalization of AChE and Na+/K+ ATPase activities. Gene-expression profile showed that cotreatment with RS to AlCl3-treated rats succeeded in exerting significant decreases in BACE1, AChE, and IL1B gene expression. Normalization of the expression of the aforementioned genes was achieved by coadministration of RLs to AlCl3-treated rats. The profound therapeutic effect of RLs over RS was evidenced by nearly preventing amyloid plaque formation, as shown in the histopathological examination of rat brain.Conclusion: RLs could be a potential drug-delivery system for ameliorating Alzheimer's disease.Keywords: rivastigmine, Alzheimer’s disease, liposomes, rats, gene expressionIsmail MFElMeshad ANSalem NADove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 393-406 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Ismail MF
ElMeshad AN
Salem NA
Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer's disease
description Manal Fouad Ismail,1 Aliaa Nabil ElMeshad,2 Neveen Abdel-Hameed Salem31Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 3Department of Narcotics and Ergogenic Aids and Poisons, National Research Center, Giza, EgyptBackground: To sustain the effect of rivastigmine, a hydrophilic cholinesterase inhibitor, nanobased formulations were prepared. The efficacy of the prepared rivastigmine liposomes (RLs) in comparison to rivastigmine solution (RS) was assessed in an aluminium chloride (AlCl3)-induced Alzheimer’s model.Methods: Liposomes were prepared by lipid hydration (F1) and heating (F2) methods. Rats were treated with either RS or RLs (1 mg/kg/day) concomitantly with AlCl3 (50 mg/kg/day).Results: The study showed that the F1 method produced smaller liposomes (67.51 ± 14.2 nm) than F2 (528.7 ± 15.5 nm), but both entrapped the same amount of the drug (92.1% ± 1.4%). After 6 hours, 74.2% ± 1.5% and 60.8% ± 2.3% of rivastigmine were released from F1 and F2, respectively. Both RLs and RS improved the deterioration of spatial memory induced by AlCl3, with RLs having a superior effect. Further biochemical measurements proved that RS and RLs were able to lower plasma C-reactive protein, homocysteine and asymmetric dimethylarginine levels. RS significantly attenuated acetylcholinesterase (AChE) activity, whereas Na+/K+-adenosine triphosphatase (ATPase) activity was enhanced compared to the AlCl3-treated animals; however, RLs succeeded in normalization of AChE and Na+/K+ ATPase activities. Gene-expression profile showed that cotreatment with RS to AlCl3-treated rats succeeded in exerting significant decreases in BACE1, AChE, and IL1B gene expression. Normalization of the expression of the aforementioned genes was achieved by coadministration of RLs to AlCl3-treated rats. The profound therapeutic effect of RLs over RS was evidenced by nearly preventing amyloid plaque formation, as shown in the histopathological examination of rat brain.Conclusion: RLs could be a potential drug-delivery system for ameliorating Alzheimer's disease.Keywords: rivastigmine, Alzheimer’s disease, liposomes, rats, gene expression
format article
author Ismail MF
ElMeshad AN
Salem NA
author_facet Ismail MF
ElMeshad AN
Salem NA
author_sort Ismail MF
title Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer's disease
title_short Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer's disease
title_full Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer's disease
title_fullStr Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer's disease
title_full_unstemmed Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer's disease
title_sort potential therapeutic effect of nanobased formulation of rivastigmine on rat model of alzheimer's disease
publisher Dove Medical Press
publishDate 2013
url https://doaj.org/article/0a5cad646838461589e4243bc5515cea
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