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 dimethylarginine 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 NaGene-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.

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

“…For AD, 26 full-text article reviews were performed, and 12 studies were included for their fulfillment of inclusion criteria ( Figure 3, Table 3). 80,[83][84][85][86][87][88][89][90][91][92][93][94][95] For PD, 19 full-text articles were reviewed, and eight articles had all the requisites to be considered here ( Figure 3, Table 3). [96][97][98][99][100][101][102][103] Unfortunately, for Huntington's disease, just one full article was analyzed and this article did not show any outcome of interest for this disease, and for this reason was not included here ( Figure 3).…”

“…It would thus be desirable to develop new formulations to avoid these side effects, and all studies proved that the use of liposomes was a good strategy in the treatment of AD. 80,86,[90][91][92]111 Intranasal delivery of rivastigmine or galantamine liposomes has been shown to be a viable and effective route to improve drug bioavailability for brain drug targeting. 80,90,92 Intranasal delivery was also used as a successful approach for delivery of liposomes containing quercetin, which has antioxidant properties.…”

“…[93][94][95] Moreover, there have been several studies exploring different strategies to block the effects of Aβ and tau proteins that constitute major hallmarks of AD. [84][85][86][87]91 Once encapsulated into liposomes, the H102 peptide, a β-sheet breaker, was able to block the early steps of aggregation and misfolding of the soluble Aβ, improving the spatial memory impairment of AD in rats. 112 α-Mangostin is a polyphenolic xanthone that exhibits pharmacological effects, such as anti-inflammation, antioxidant, and antitumor effects.…”

The Use of Operant Tasks to Assess Cognition in Persons with Alzheimer’s Disease

“…Most notably impaired in AD are memory and language; however, other features include impairment in learning, attention, time perception, and planning (Buck et al, 1997;Coubard et al, 2011;O'Brien et al, 2009). Studies in animal models have identified numerous interventions that have demonstrated potential to attenuate some of the cognitive deficits associated with AD, (Abd-El-Fattah et al, 2014;Eketjall et al, 2013;Ismail et al, 2013;Liu et al, 2014;Long et al, 2013;Nagakura et al, 2013;Sierksma et al, 2013). Unfortunately, many of these interventions have not been proven effective in humans (Day et al, 2008;Franco & CedazoMinguez, 2014;Zeiss, 2014).…”

Nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease

“…Though the rivastigmine solution significantly attenuated AChE activity, rivastigmine-loaded liposomes succeeded in normalizing AChE. 38 The delivery of liposomes to the brain can be attained via the intranasal route to overcome the BBB, 169,281,282 and liposomes can cross the BBB by transport lipid-mediated free diffusion or lipid-mediated endocytosis. 283 Rivastigmineloaded liposomes were prepared using the lipid hydration method for delivery into the brain via the intranasal route.…”