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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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) |
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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 |
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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 |
work_keys_str_mv |
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