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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2013
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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. |
format | Online Article Text |
id | pubmed-3558309 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
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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