RESUMEN
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 (Aß) aggregation was evaluated in Aß 1-42 treated cells with thioflavin T (ThT). The behavioral acquisition effects were evaluated in Aß 1-42 (5 µg/ 5 µL, 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.