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

BACKGROUND: 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 (AlCl(3))-induced Alzheimer’s m...

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Autores principales: Ismail, Manal Fouad, ElMeshad, Aliaa Nabil, Salem, Neveen Abdel-Hameed
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3558309/
https://www.ncbi.nlm.nih.gov/pubmed/23378761
http://dx.doi.org/10.2147/IJN.S39232
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author Ismail, Manal Fouad
ElMeshad, Aliaa Nabil
Salem, Neveen Abdel-Hameed
author_facet Ismail, Manal Fouad
ElMeshad, Aliaa Nabil
Salem, Neveen Abdel-Hameed
author_sort Ismail, Manal Fouad
collection PubMed
description BACKGROUND: 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 (AlCl(3))-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 AlCl(3) (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 AlCl(3), 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 dimethy-larginine levels. RS significantly attenuated acetylcholinesterase (AChE) activity, whereas Na(+)/K(+)-adenosine triphosphatase (ATPase) activity was enhanced compared to the AlCl(3)-treated animals; however, RLs succeeded in normalization of AChE and Na(+)/K(+) ATPase activities. Gene-expression profile showed that cotreatment with RS to AlCl(3)-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 AlCl(3)-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.
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spelling pubmed-35583092013-02-01 Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer’s disease Ismail, Manal Fouad ElMeshad, Aliaa Nabil Salem, Neveen Abdel-Hameed Int J Nanomedicine Original Research BACKGROUND: 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 (AlCl(3))-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 AlCl(3) (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 AlCl(3), 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 dimethy-larginine levels. RS significantly attenuated acetylcholinesterase (AChE) activity, whereas Na(+)/K(+)-adenosine triphosphatase (ATPase) activity was enhanced compared to the AlCl(3)-treated animals; however, RLs succeeded in normalization of AChE and Na(+)/K(+) ATPase activities. Gene-expression profile showed that cotreatment with RS to AlCl(3)-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 AlCl(3)-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. Dove Medical Press 2013 2013-01-23 /pmc/articles/PMC3558309/ /pubmed/23378761 http://dx.doi.org/10.2147/IJN.S39232 Text en © 2013 Ismail et al, publisher and licensee Dove Medical Press Ltd This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
spellingShingle Original Research
Ismail, Manal Fouad
ElMeshad, Aliaa Nabil
Salem, Neveen Abdel-Hameed
Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer’s disease
title 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_short 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
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3558309/
https://www.ncbi.nlm.nih.gov/pubmed/23378761
http://dx.doi.org/10.2147/IJN.S39232
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