title: Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer's disease.
abstract: 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.
  
  
  CONCLUSIONS
  RLs could be a potential drug-delivery system for ameliorating Alzheimer's disease.
authors: Department of Biochemistry, Cairo University, Cairo, Egypt. manalfouad1@yahoo.com
authors: Manal Fouad
authors: MF
authors: Ismail
authors: Aliaa Nabil
authors: AN
authors: Elmeshad
authors: Neveen Abdel-Hameed
authors: NA
authors: Salem
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood / Q000378:metabolism; D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D002712:Chlorides; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D048448:Phenylcarbamates / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D000068836:Rivastigmine
chemical_list: D017607:Aluminum Compounds; D002712:Chlorides; D008081:Liposomes; D048448:Phenylcarbamates; D000077410:Aluminum Chloride; D002097:C-Reactive Protein; D000110:Acetylcholinesterase; D000068836:Rivastigmine
keywords: Alzheimer’s disease; gene expression; liposomes; rats; rivastigmine
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