With the increasing ageing population and progressive nature of the disease, Alzheimer's disease (AD) poses to be an oncoming epidemic with limited therapeutic strategies. It is characterized by memory loss, behavioral instability, impaired cognitive function, predominantly, cognitive inability manifested due to the accumulation of β-amyloid, with malfunctioned cholinergic system. Rivastigmine, a reversible dual cholinesterase inhibitor is more tolerable and widely used choice of drug for AD. However, rivastigmine being hydrophilic and undergoing first pass metabolism, exhibits low CNS bioavailability. Nanoformulations including liposomes and PLGA nanoparticles can encapsulate hydrophilic drugs and deliver efficiently to brain. Besides, the nasal route is receiving considerable attention recently, due to its direct access to brain. Therefore, the present study attempts to evaluate the pharmacokinetic and pharmacodynamic properties of nasal liposomal and PLGA nanoparticle formulations of rivastigmine in scopolamine induced amnesia model and validate the best formulation by employing pharmacokinetic and pharmacodynamic (PK-PD) modelling. Nasal liposomal rivastigmine formulation showed the best pharmacokinetic features with rapid onset of action (Tmax=5 minutes), higher Cmax (1489.5 ± 620.71), enhanced systemic bioavailability (F=118.65 ± 23.54; AUC= 35921.75 ± 9559.46), increased half-life (30.92 ± 8.38 minutes), and reduced clearance rate (Kel (1/min) = 0.0224 ± 0.006) compared to oral rivastigmine (Tmax= 15 minutes; Cmax= 56.29 ± 27.05; F=4.39 ± 1.82; AUC=1663.79 ± 813.54; t1/2= 13.48 ± 5.79; Kel (1/min) =0.0514 ± 0.023). Further, the liposomal formulation significantly rescued the memory deficit induced by scopolamine superior to other formulations as assessed in Morris water maze and passive avoidance tasks. PK-PD modelling demonstrated strong correlation between the pharmacokinetic parameters and acetylcholinesterase inhibition of liposomal formulation.