RGD Reference Report - Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer's disease. - Rat Genome Database

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

Authors: Ismail, Manal Fouad  Elmeshad, Aliaa Nabil  Salem, Neveen Abdel-Hameed 
Citation: Ismail MF, etal., Int J Nanomedicine. 2013;8:393-406. doi: 10.2147/IJN.S39232. Epub 2013 Jan 23.
RGD ID: 13792819
Pubmed: PMID:23378761   (View Abstract at PubMed)
PMCID: PMC3558309   (View Article at PubMed Central)
DOI: DOI:10.2147/IJN.S39232   (Journal Full-text)


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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Alzheimer's disease treatmentISOIl1b (Rattus norvegicus)13792819; 13792819 RGD 
Alzheimer's disease treatmentIEP 13792819 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il1b  (interleukin 1 beta)

Genes (Mus musculus)
Il1b  (interleukin 1 beta)

Genes (Homo sapiens)
IL1B  (interleukin 1 beta)


Additional Information