Asiatic Acid Fabricated Nanoconstructs to Mitigate Amyloid Beta1-42 Induced Injury in SH-SY5Y Cells In-Vitro and Ameliorates Cognitive Impairment by Dual Cholinesterase Inhibition and Attenuation of Oxidative Stress In-Vivo

Purpose Asiatic acid (AA) is reported for its neuroprotective potential in Alzheimer's disease (AD). This present work aimed to develop AA loaded nanostructured lipid carriers (AAN) for targeting the delivery of AA into the brain and ameliorating the cognitive deficits in AD rats. Methods AAN was optimized using the Box-Behnken design, considering 3 factors (soya lecithin, tween 80, and high pressure homogenizer (HPH) pressure) as independent variables while particle size (PS), zeta potential (ZP) and entrapment efficiency (EE) were dependent variables. Cytotoxicity assay and internalization studies of AAN were evaluated in SH-SY5Y cells and further neuroprotective efficiency on intracellular amyloid beta (A beta) aggregation was evaluated in A beta (1-42) treated cells with thioflavin T (ThT). The behavioral acquisition effects were evaluated in A beta (1-42) (5 mu g/ 5 mu L, intracerebroventricular (ICV), unilateral) induced AD model followed by the histology and quantification of neurotransmitters levels. Results The optimized AAN revealed desired PS (44.1 +/- 12.4 nm), ZP (- 47.1 +/- 0.017 mv) and EE (73.41 +/- 2.53%) for brain targeting delivery of AA. In-vitro, AAN exhibited better neuroprotective potential than AA suspension (AAS). AA content was 1.28 folds and 2.99 folds heightened in plasma and brain respectively after the i.p. administration of AAN as compared to AAS. The results of pharmacodynamic studies manifested the AAN treatment significantly (p < 0.05) ameliorated the cognitive deficits. Conclusions Hence, developed AAN has neuroprotective potential and should be further considered as an unconventional platform in preclinical model for the management of AD.

Automated summary

This study developed nanostructured lipid carriers loaded with Asiatic acid (AA) for targeted delivery to the brain and improvement of cognitive deficits in Alzheimer's disease (AD) rats. The optimized carriers showed desired particle size, zeta potential, and entrapment efficiency for brain targeting delivery. In vitro experiments demonstrated better neuroprotective potential of the carriers compared to AA suspension. Pharmacokinetic studies showed increased AA content in plasma and brain after administration of the carriers. The treatment with the carriers significantly improved cognitive deficits in AD rats.